bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of Chromosome Translocations in Cancer
Authors: Nickoloff Jac A 
Published: May 2017

Abstract

Chromosome translocations have long been known to be causative events in cancer. First observed as recurrent translocations in lymphomas and leukaemias, translocations are also found in solid tumours. One of the key hallmarks of cancer is genome instability, and chromosome translocations represent a critical form of genome instability that reflects mis‐repair of DNA double‐strand breaks (DSBs). DSBs are repaired by two main pathways, non‐homologous end joining and homologous recombination, and chromosome translocations can be created by both of these pathways. Many translocations associated with specific cancers are recurrent, reflecting selective pressure for inactivated tumour suppressor genes or activated oncogenes, which are early drivers of cancer phenotypes. Cancer therapeutics, including DNA reactive chemicals, topoisomerase inhibitors and radiation, are effective cancer treatments, but they can induce translocation‐mediated secondary malignancies at significant frequencies. Reducing the risk of these sequelae is an important goal in cancer research.

Key Concepts

Chromosome translocations are critical genomic rearrangements that are frequently found in lymphoid and solid tumours and other diseases.

Translocations arise when DNA double‐strand breaks arise simultaneously on two separate chromosomes and are mis‐rejoined.

Translocations observed in cancer may inactivate tumour suppressor genes or activate oncogenes by gene fusion or juxtaposition of a strong promoter with a proto‐oncogene.

Translocations are formed primarily through alternative non‐homologous end joining, but other double‐strand break repair mechanisms can contribute to translocation spectra, including classical non‐homologous end joining, homologous recombination and single‐strand annealing.

Cancer therapeutics may cause translocations that generate secondary, therapy‐induced cancers.

Translocation efficiency and junction positions are regulated by many factors including programmed DNA double‐strand breaks, spontaneous and induced DNA damage, DNA repair pathways, structural elements in DNA sequences such as repeated sequences and palindromes, relative locations chromosomes within nuclei and epigenetic factors.
A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY‐PD III)
Authors: Biglan Kevin M. , Oakes David , Lang Anthony E. , Hauser Robert A. , Hodgeman Karen , Greco Brittany , Lowell Jillian , Rockhill Rebecca , Shoulson Ira , Venuto Charles , Young Diony , Simuni Tanya ,   the Parkinson Study Group STEADY‐PD III Investigators
Published: May 2017

AbstractObjectiveTo describe the rationale for a novel study design and baseline characteristics of a disease‐modifying trial of isradipine 10 mg daily in early Parkinson disease (PD).MethodsSTEADY‐PDIII is a 36‐month, Phase 3, parallel group, placebo‐controlled study of the efficacy of isradipine 10 mg daily in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I‐III score in the practically defined ON state. Secondary outcome measures include clinically meaningful measures of disability progression in early PD: (1) Time to initiation and utilization of dopaminergic therapy; (2) Time to onset of motor complications; (3) Change in nonmotor disability. Exploratory measures include global measures of functional disability, quality of life, change in the ambulatory capacity, cognitive function, and pharmacokinetic analysis. Rationale for the current design and alternative design approaches are discussed.ResultsThe entire cohort of 336 participants was enrolled at 55 Parkinson Study Group sites in North America. The percentage of male participants were 68.5% with a mean age of 61.9 years (sd 9.0), mean Hoehn and Yahr stage of 1.7 (sd 0.5), mean UPDRS total of 23.1 (sd 8.6), and MoCA of 28.1 (sd 1.4).InterpretationSTEADY‐PD III has a novel and innovative design allowing for the determination of longer duration benefits on clinically relevant outcomes in a relatively small cohort on top of the benefit derived from symptomatic therapy. Baseline characteristics are similar to those in previously enrolled de novo PD trials. This study represents a unique opportunity to evaluate the potential impact of a novel therapy to slow progression of PD disability and provide clinically meaningful benefits.
Noise covariance matrices in state‐space models: A survey and comparison of estimation methods—Part I
Authors: Duník Jindřich , Straka Ondřej , Kost Oliver , Havlík Jindřich 
Published: May 2017

SummaryThis paper deals with the estimation of the noise covariance matrices of systems described by state‐space models. Stress is laid on the systematic survey and classification of both the recursive and batch processing methods proposed in the literature with a special focus on the correlation methods. Besides the correlation methods, representatives of other groups are introduced also with respect to their basic idea, estimate properties, assumptions and possible extensions, and user‐defined parameters. Common and dual properties of the methods are highlighted, and a simulation comparison using exemplary MATLAB implementations of the methods is provided.
Catalytic Asymmetric 1,2‐Difunctionalization of Indolenines with α‐(Benzothiazol‐2‐ylsulfonyl) Carbonyl Compounds
Authors: Shao You‐Dong , Cheng Dao‐Juan 
Published: May 2017

AbstractA novel catalytic asymmetric 1,2‐difunctionalization reaction of indolenines with α‐(benzothiazol‐2‐ylsulfonyl) carbonyl compounds was developed. By employing the strategy of Brønsted acid‐assisted chiral phosphoric acid catalysis, the Mannich addition/Smiles rearrangement cascade occurred smoothly and provided a new family of optically active 1,2‐difunctionalized 2‐substituted indolines in good yields and enantioselectivities.magnified image
Mutagenesis‐Independent Stabilization of Class B Flavin Monooxygenases in Operation
Authors: Goncalves Leticia C. P. , Kracher Daniel , Milker Sofia , Fink Michael J. , Rudroff Florian , Ludwig Roland , Bommarius Andreas S. , Mihovilovic Marko D. 
Published: May 2017

AbstractThis paper describes the stabilization of flavin‐dependent monooxygenases under reaction conditions, using an engineered formulation of additives (the natural cofactors NADPH and FAD, and superoxide dismutase and catalase as catalytic antioxidants). This way, a 103‐ to 104‐fold increase of the half‐life was reached without resource‐intensive directed evolution or structure‐dependent protein engineering methods. The stabilized enzymes are highly valued for their synthetic potential in biotechnology and medicinal chemistry (enantioselective sulfur, nitrogen and Baeyer–Villiger oxidations; oxidative human metabolism), but widespread application was so far hindered by their notorious fragility. Our technology immediately enables their use, does not require structural knowledge of the biocatalyst, and creates a strong basis for the targeted development of improved variants by mutagenesis.magnified image
Efficient Access to the Functionalized Bicyclic Pharmacophore of Spirolide C by Using a Selective Diels–Alder Reaction
Authors: Tsuchikawa Hiroshi , Minamino Kou , Hayashi Sho , Murata Michio 
Published: May 2017

AbstractA functionalized bicyclic lactam that was used as a key intermediate in an efficient synthesis of the pharmacophore of potent marine toxin spirolide C was synthesized by using a highly selective Diels–Alder reaction. To improve the reactivity of this transformation without loss of selectivity, substrates that contained a silyl ether or silatrane moiety were elaborately designed and converted into the spirobicyclic core structure with stereochemical control over the two asymmetric centers at the C7 and C29 positions. Moreover, a further C−C bond formation by using a Hiyama cross‐coupling reaction of the vinyl silatrane derivative facilitated versatile modification at the C5 position with an aryl or alkenyl substituent.
Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke
Authors: Lansberg Maarten G. , Christensen Soren , Kemp Stephanie , Mlynash Michael , Mishra Nishant , Federau Christian , Tsai Jenny P. , Kim Sun , Nogueria Raul G. , Jovin Tudor , Devlin Thomas G. , Akhtar Naveed , Yavagal Dileep R. , Haussen Diogo , Dehkharghani Seena , Bammer Roland , Straka Matus , Zaharchuk Greg , Marks Michael P. , Albers Gregory W. ,   for the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Investigators
Published: May 2017

ObjectiveTo assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.MethodsWe conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as “target mismatch” if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36‐hour follow‐up magnetic resonance imaging.ResultsOf the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1–20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5–27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4–140).InterpretationThe robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849–856
A Near‐Infrared Dye That Undergoes Multiple Interconversions through Acid–Base Equilibrium and Reversible Redox Processes
Authors: Asai Kengo , Fukazawa Aiko , Yamaguchi Shigehiro 
Published: May 2017

AbstractA near‐infrared (NIR) polymethine dye (1), consisting of a cyclohepta[1,2‐b;4,3‐b′]dithiophene and two phenol moieties, was synthesized. This dye exhibited pH‐responsive changes in its photophysical properties due to a two‐step acid–base equilibrium that produced a protonated cation (1H+) and an anion (1−). While 1H+ showed an intense fluorescence in the red region of the visible spectrum, 1− exhibited a strong absorption in the NIR region. The tropylium ion character in 1H+ induces high pKa1 and pKa2 values for 1. Moreover, a stable radical (1.) was prepared, which showed a NIR absorption band with a maximum at circa 1600 nm. The cyclic voltammogram of 1. revealed a two‐step reversible redox process that produced 1− and the cation 1+, which is different from 1H+. These redox processes accompany drastic electrochromic changes in the vis–NIR region. Overall, 1 is susceptible to multiple interconversions between five forms, due to the multifaceted character of the cycloheptadithiophene skeleton.
In‐Cell Dual Drug Synthesis by Cancer‐Targeting Palladium Catalysts
Authors: Clavadetscher Jessica , Indrigo Eugenio , Chankeshwara Sunay V. , Lilienkampf Annamaria , Bradley Mark 
Published: May 2017

AbstractTransition metals have been successfully applied to catalyze non‐natural chemical transformations within living cells, with the highly efficient labeling of subcellular components and the activation of prodrugs. In vivo applications, however, have been scarce, with a need for the specific cellular targeting of the active transition metals. Here, we show the design and application of cancer‐targeting palladium catalysts, with their specific uptake in brain cancer (glioblastoma) cells, while maintaining their catalytic activity. In these cells, for the first time, two different anticancer agents were synthesized simultaneously intracellularly, by two totally different mechanisms (in situ synthesis and decaging), enhancing the therapeutic effect of the drugs. Tumor specificity of the catalysts together with their ability to perform simultaneous multiple bioorthogonal transformations will empower the application of in vivo transition metals for drug activation strategies.
Ligand‐Enabled Auxiliary‐Free meta‐C−H Arylation of Phenylacetic Acids
Authors: Li Gen‐Cheng , Wang Peng , Farmer Marcus E. , Yu Jin‐Quan 
Published: May 2017

AbstractThe meta‐C−H arylation of free phenylacetic acid was realized using 2‐carbomethoxynorbornene (NBE‐CO2Me) as a transient mediator. Both the modified norbornene and the mono‐protected 3‐amino‐2‐hydroxypyridine type ligand are crucial for this auxiliary‐free meta‐C−H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta‐arylated products in high yields.
An Orbital‐Overlap Complement to Atomic Partial Charge
Authors: Mehmood Arshad , Janesko Benjamin G. 
Published: May 2017

AbstractAtomic partial charges are widely used to predict reactivity. Partial charge alone is often insufficient: the carbons of benzene and cyclobutadiene, or those of diamond, graphene, and C60, possess nearly identical partial charges and very different reactivities. Our atomic overlap distance complements computed partial charges by measuring the size of orbital lobes that best overlap with the wavefunction around an atom. Compact, chemically stable atoms tend to have overlap distances smaller than chemically soft, unstable atoms. We show here how combining atomic charges and overlap distances captures trends in aromaticity, nucleophilicity, allotrope stability, and substituent effects. Applications to recent experiments in organic chemistry (counterintuitive Lewis base stabilization of alkenyl anions in anionic cyclization) and nanomaterials chemistry (facile doping of the central atom in Au7 hexagons) illustrate this combination's predictive power.
Strain Coupling of Conversion‐type Fe3O4 Thin Films for Lithium Ion Batteries
Authors: Hwang Sooyeon , Meng Qingping , Chen Ping‐Fan , Kisslinger Kim , Cen Jiajie , Orlov Alexander , Zhu Yimei , Stach Eric A. , Chu Ying‐Hao , Su Dong 
Published: May 2017

AbstractLithiation/delithiation induces significant stresses and strains into the electrodes for lithium ion batteries, which can severely degrade their cycling performance. Moreover, this electrochemically induced strain can interact with the local strain existing at solid–solid interfaces. It is not clear how this interaction affects the lithiation mechanism. The effect of this coupling on the lithiation kinetics in epitaxial Fe3O4 thin film on a Nb‐doped SrTiO3 substrate is investigated. In situ and ex situ transmission electron microscopy (TEM) results show that the lithiation is suppressed by the compressive interfacial strain. At the interface between the film and substrate, the existence of LixFe3O4 rock‐salt phase during lithiation consequently restrains the film from delamination. 2D phase‐field simulation verifies the effect of strain. This work provides critical insights of understanding the solid–solid interfaces of conversion‐type electrodes.
Light‐Induced Bidirectional Metal‐to‐Metal Charge Transfer in a Linear Fe2Co Complex
Authors: Hu Ji‐Xiang , Luo Lun , Lv Xiao‐Jin , Liu Lei , Liu Qiang , Yang Yi‐Kai , Duan Chun‐Ying , Luo Yi , Liu Tao 
Published: May 2017

AbstractIt is a challenge to reversibly switch both magnetism and polarity using light irradiation. Herein we report a linear Fe2Co complex, whereby interconversion between FeIIILS(μ‐CN)CoIIHS(μ‐NC)FeIIILS (LS=low‐spin, HS=high‐spin) and FeIIILS(μ‐CN)CoIIILS(μ‐NC)FeIILS linkages could be achieved upon heating and cooling, or alternating laser irradiation at 808 and 532 nm. The electron spin arrangement and charge distribution were simultaneously tuned accompanying bidirectional metal‐to‐metal charge transfer, providing switchable polarity and magnetism in the complex.
Porphyrin Bound to i‐Motifs: Intercalation versus External Groove Binding
Authors: Qin Tingxiao , Liu Kunhui , Song Di , Yang Chunfan , Su Hongmei 
Published: May 2017

AbstractG‐rich and C‐rich DNA can fold into the tetrastranded helical structures G quadruplex or C quadruplex (i‐motif), which are considered to be specific drug targets for cancer therapy. A large number of small molecules (so‐called ligands), which can bind and modulate the stability of G quadruplex structures, have been widely examined. Much less is known, however, about the ligand binding interactions with the C quadruplex (i‐motif). By combining steady‐state measurements (UV/Vis, fluorescence, and induced circular dichroism (ICD)) with time‐resolved laser flash photolysis spectroscopy, we have studied the binding interactions of cationic porphyrin (5,10,15,20‐tetrakis(N‐methylpyridinium‐4‐yl)‐21 H,23 H‐porphyrin, abbreviated as TMPyP4) with i‐motifs (C3TA2)3C3T and (C4A4C4)2. The intercalation binding mode through π–π stacking of the porphyrin macrocycle and the C:C+ hemiprotonated base pair has been identified for the first time. The coexistent binding modes of intercalation (≈80 %) versus external major‐groove binding (≈20 %) have been determined quantitatively, thereby allowing a fuller understanding of the porphyrin–i‐motif interactions. The ionic strength was found to play an important role in affecting affects the binding modes, with the progressive increase in the ionic strength resulting in the gradual decrease in the intercalation percentage and an increase in the groove‐binding percentage. Furthermore, an extended study of the porphyrin derivative with four bulky side‐arm substituents (T4) suggests a complete prohibition of the intercalation mode owing to large steric hindrance, thereby providing a novel groove‐binding ligand with site selectivity. These results provide in‐depth mechanistic insights to better understand the ligand interactions with i‐motifs and guidance for related applications in anticancer drug design.
Methanol as carbon substrate in the bio‐economy: Metabolic engineering of aerobic methylotrophic bacteria for production of value‐added chemicals
Authors: Pfeifenschneider Johannes , Brautaset Trygve , Wendisch Volker F. 
Published: May 2017

AbstractBacteria are widely used as cell factories for production of enzymes and chemicals, mostly from sugars. Methylotrophic bacteria can utilize the one‐carbon compound methanol as sole carbon source for growth, and metabolic engineering is being used to develop bioprocesses based on these organisms for conversion of methanol into value‐added chemicals. Methylotrophic model strains include both Gram‐positive and Gram‐negative bacteria and in all cases methanol metabolism proceeds via the cell‐toxic intermediate formaldehyde. Thus, understanding the genetics, biochemistry, and regulation of methylotrophic pathways is crucial for successful strain development and for their concomitant fermentations. Also, such basic knowledge has proven useful for design of strategies and approaches for the rational transfer of methylotrophy into non‐methylotrophic bacteria. In the current review we highlight the best studied methylotrophic model organisms, with particular focus on the Gram‐positive Bacillus methanolicus and the Gram‐negative Methylobacterium extorquens, including their genetics and physiology. We present successful metabolic engineering examples leading to the construction of recombinant strains for the production of amino acids, platform chemicals, terpenoids and dicarboxylic acids derivatives from methanol as sole carbon source. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd
Advances in the use of genetically modified plant biomass for biodiesel generation
Authors: Wan Shen , Truong‐Trieu Victoria MT , Ward Tonya , Whalen Joann K. , Altosaar Illimar 
Published: May 2017

AbstractBiodiesel is a low‐carbon‐intensity renewable fuel with up to 99% lower greenhouse gas emissions than petroleum‐based diesel. The use of oil crops for biodiesel is under critical examination. It is expensive and suffers from the food versus fuel risk/benefit problem. Consequently, many countries (e.g. Malaysia and countries in the EU) are scaling back the use of oil crops as feedstock for biofuel production. The limitations of these traditional crops are leading the renewable fuels industry to consider innovative, sustainable, and profitable biomass‐based platforms. Plant genetic engineering and other new breeding technologies are essential for developing such biomass‐based platforms because they enhance plant tolerance to abiotic and biotic stresses, resulting in higher feedstock yields, greater net energy gain, and the generation of high‐value co‐products. We review and summarize the recent improvements of oil crops through plant genetic engineering that may increase widespread and cost‐effective production of biodiesel and value‐added co‐products for green chemistry applications. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd
Das Nieuwe Provinciehuis in Antwerpen
Authors: Jansen Wim , De Rycke Klaas , Eppenschwandtner Martin , Eisenbach Philipp 
Published: May 2017

AbstractErst in der autonomen Region Flandern, später im ganzen Land, besteht in Belgien seit der Einführung des „Bouwmeesters” (1995) ein hoher Anspruch an eine neue Architekturkultur. Der Baumeister kümmert sich um die architektonische Qualität von öffentlichen und halböffentlichen Bauprojekten. Sein wichtigstes Instrument ist dabei das Open‐Call‐System, welches bei einer entsprechenden Ausschreibung zunächst die architektonische Haltung eines Büros abfragt. Erst nach Auswahl eines Büros muss dieses einen konkreten Vorschlag ausarbeiten. Das eröffnet auch jungen Architekturbüros Chancen, mit wenig Aufwand ihr Können zu beweisen. Das Provinciehuis in Antwerpen ist auf diese Weise aus einem „open oproep”‐Wettbewerb hervorgegangen. Kennzeichnend für dieses 58 m hohe Gebäude ist seine leichte Verdrehung. Ausgeführt in Ortbetonbauweise in Sichtbeton, dürfte der Neubau für belgische Verhältnisse als ungewöhnlich gelten, werden doch die meisten Hochhäuser in Belgien üblicherweise in Fertigbetonbauweise erstellt.