bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insertion of CO2 Mediated by a (Xantphos)NiI–Alkyl Species
Authors: Diccianni Justin B. , Hu Chunhua T. , Diao Tianning 
Published: July 2019

AbstractThe incorporation of CO2 into organometallic and organic molecules represents a sustainable way to prepare carboxylates. The mechanism of reductive carboxylation of alkyl halides has been proposed to proceed through the reduction of NiII to NiI by either Zn or Mn, followed by CO2 insertion into NiI‐alkyl species. No experimental evidence has been previously established to support the two proposed steps. Demonstrated herein is that the direct reduction of (tBu‐Xantphos)NiIIBr2 by Zn affords NiI species. (tBu‐Xantphos)NiI‐Me and (tBu‐Xantphos)NiI‐Et complexes undergo fast insertion of CO2 at 22 °C. The substantially faster rate, relative to that of NiII complexes, serves as the long‐sought‐after experimental support for the proposed mechanisms of Ni‐catalyzed carboxylation reactions.
Synthesis of Homoallylic Alcohols with Acyclic Quaternary Centers through CoIII‐Catalyzed Three‐Component C−H Bond Addition to Internally Substituted Dienes and Carbonyls
Authors: Dongbang Sun , Shen Zican , Ellman Jonathan A. 
Published: July 2019

AbstractAn efficient CoIII‐catalyzed three‐component strategy to prepare homoallylic alcohols containing acyclic quaternary centers is disclosed. This transformation enables the introduction of two C−C σ bonds through C−H bond activation and sequential addition to internally substituted dienes and a wide range of aldehydes and activated ketones. Isoprene and other internally monosubstituted dienes are effective inputs, with the reaction proceeding with high diastereoselectivity for those substrate combinations that result in more than one stereogenic center. Moreover, the opposite relative stereochemistry can be achieved by employing 1,2‐disubstituted dienes. A mechanism for the transformation is proposed based upon the relative stereochemistry of the products and studies with isotopically labeled starting materials.
Topotactic Synthesis of Phosphabenzene‐Functionalized Porous Organic Polymers: Efficient Ligands in CO2Conversion
Authors: Yang Zhenzhen , Chen Hao , Li Bo , Guo Wei , Jie Kecheng , Sun Yifan , Jiang De‐en , Popovs Ilja , Dai Sheng 
Published: July 2019

AbstractProgress toward the preparation of porous organic polymers (POPs) with task‐specific functionalities has been exceedingly slow—especially where polymers containing low‐oxidation phosphorus in the structure are concerned. A two‐step topotactic pathway for the preparation of phosphabenzene‐based POPs (Phos‐POPs) under metal‐free conditions is reported, without the use of unstable phosphorus‐based monomers. The synthetic route allows additional functionalities to be introduced into the porous polymer framework with ease. As an example, partially fluorinated Phos‐POPs (F‐Phos‐POPs) were obtained with a surface area of up to 591 m2 g−1. After coordination with Ru species, a Ru/F‐Phos‐POPs catalyst exhibited high catalytic efficiency in the formylation of amines (turnover frequency up to 204 h−1) using a CO2/H2mixture, in comparison with the non‐fluorinated analogue (43 h−1) and a Au/TiO2heterogeneous catalysts reported previously (<44 h−1). This work describes a practical method for synthesis of porous organic phosphorus‐based polymers with applications in transition‐metal‐based heterogeneous catalysis.
Synthesis of Indolines and Derivatives by Aza‐Heck Cyclization
Authors: Xu Feiyang , Korch Katerina M. , Watson Donald A. 
Published: July 2019

AbstractFor the first time, an aza‐Heck cyclization that allows the preparation of indoline scaffolds is described. Using N‐hydroxy anilines as electrophiles, which can be easily accessed from the corresponding nitroarenes, this method provides indolines bearing pendant functionality and complex ring topologies. Synthesis of challenging indolines, such as those bearing fully substituted carbon atoms at C2, is also possible using this method.
What Level of Inflammation Leads to Structural Damage in the Sacroiliac Joints? A Four‐Year Magnetic Resonance Imaging Follow‐Up Study of Low Back Pain Patients
Authors: Arnbak Bodil , Jensen Tue S. , Schiøttz‐Christensen Berit , Pedersen Susanne J. , Østergaard Mikkel , Weber Ulrich , Hendricks Oliver , Zejden Anna , Manniche Claus , Jurik Anne G. 
Published: July 2019

ObjectiveSacroiliac (SI) joint bone marrow edema (BME) is considered to be pivotal in the detection of early spondyloarthritis. However, the link between BME and development of spondyloarthritis‐related bone remodeling remains unclear. This study was undertaken to investigate the evolution of BME and structural lesions in the SI joints over time.MethodsBaseline and 4‐year follow‐up magnetic resonance imaging scans were conducted in 604 patients ages 18–40 years who were referred with low back pain to an outpatient spine clinic. Eight SI joint regions were scored for BME and categorized as absent, limited (<25% of subcortical bone region), intermediate (25–50%), or extensive (>50%). Structural lesions including erosions and fat lesions were scored as absent or present.ResultsSI joint BME was seen at either time point (baseline or at 4 years) in 41% of participants but was persistent at both time points in only 16% of participants. Structural SI joint lesions developed according to the extent of BME at baseline: limited, intermediate, and extensive BME (as compared to absent BME) were independently associated with erosion at follow‐up with odds ratios (ORs) of 3, 5, and 46, respectively, and with fat lesions (ORs 3, 7, and 33, respectively). In regions with limited and intermediate BME at baseline, 60% and 50% had resolved by follow‐up, respectively, while only 2% and 7% had evolved into extensive BME by follow‐up.ConclusionWhile extensive SI joint BME was a strong independent predictor of development of structural lesions, limited and intermediate BME were mostly transient and only rarely evolved into extensive BME or structural lesions. These findings enhance our understanding of the natural development of SI joint lesions and indicate different progression patterns for limited/intermediate versus extensive BME, possibly due to different etiologies.
Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis
Authors: Kozlova Anastasiia , Pachera Elena , Maurer Britta , Jüngel Astrid , Distler Jörg H. W. , Kania Gabriela , Distler Oliver 
Published: July 2019

ObjectiveTo analyze the expression, regulation, and role of microRNA‐125b (miR‐125b) in systemic sclerosis (SSc).MethodsMiR‐125b expression was assessed by quantitative polymerase chain reaction (qPCR) of RNA from dermal fibroblasts and whole skin biopsy specimens from healthy controls and SSc patients. To identify downstream effectors, RNA from healthy control fibroblasts was sequenced after miR‐125b knockdown and further validated using qPCR and Western blotting. Fibrosis, apoptosis, and proliferation were assessed by Caspase‐Glo 3/7 assay, Western blotting, immunofluorescence staining for cleaved caspase 3, and annexin V real‐time assay in dermal fibroblasts.ResultsExpression of miR‐125b was significantly down‐regulated in SSc skin biopsy specimens by 53% (median fold change 0.47 [interquartile range 0.35–0.69]; P < 0.001) and in SSc dermal fibroblasts by 47% (median fold change 0.53 [interquartile range 0.36–0.58]; P < 0.001) compared to healthy control skin biopsy specimens and fibroblasts, respectively (n = 10 samples per group). Treatment with the histone deacetylase inhibitors trichostatin A and tubastatin A significantly decreased the expression of miR‐125b in dermal fibroblasts. MiR‐125b knockdown significantly reduced cell proliferation and α‐smooth muscle actin (α‐SMA) expression at the messenger RNA (mRNA) and protein levels. RNA‐Seq identified BAK1, BMF, and BBC3 as potential targets of miR‐125b. Quantitative PCR confirmed that knockdown of miR‐125b up‐regulated these genes (P < 0.01; n = 12). Bcl‐2 homologous antagonist killer 1 showed the strongest induction confirmed at the protein level (P < 0.01; n = 10). Consequently, miR‐125b knockdown increased apoptosis compared to scrambled control. Accordingly, miR‐125b overexpression decreased apoptosis.ConclusionOur findings indicate that miR‐125b is down‐regulated in SSc skin and primary dermal fibroblasts. MiR‐125b down‐regulation increases apoptosis and decreases proliferation and α‐SMA expression in dermal fibroblasts, indicating that its compensatory, antifibrotic mechanism may be a potential novel therapeutic option.
The iterated extended set membership filter applied to relative localization between autonomous vehicles based on GNSS and UWB ranging
Authors: Bolting Jan , Fergani Soheib 
Published: July 2019

AbstractThis paper presents a novel Iterated Extended Set Membership Filter (IESMF) with an application to relative localization. For safe operation of formations of automatic vehicles, consistent uncertainty estimates are of crucial importance. Here, a localization filter that provides ellipsoidal regions that are guaranteed to contain another vehicles position is presented. The proposed iterative update step can appreciably reduce the size of the a posteriori state ellipsoid. The idea of using SIVIA as a baseline to quantify conservativeness is introduced. Another novelty is that we take into account parametric uncertainty of the observation equation.The proposed filter is applied to a two unmanned aircraft systems (UAS) localization problem in simulation with observation noise obtained from real sensors. Simulation results illustrate the effective reduction of filter conservativeness by a small number of iterative updates.
Mechanism and Inhibitor Exploration with Binuclear Mg Ketol‐Acid Reductoisomerase: Targeting the Biosynthetic Pathway of Branched‐Chain Amino Acids
Authors: Yu Ming‐Jia , Wu Jue , Chen Shi‐Lu 
Published: July 2019

AbstractBinuclear Mg ketol‐acid reductoisomerase (KARI), which converts (S)‐2‐acetolactate into (R)‐2,3‐dihydroxyisovalerate, is responsible for the second step of the biosynthesis of branched‐chain amino acids in plants and microorganisms and thus serves as a key inhibition target potentially without effects on mammals. Here, through the use of density functional calculations and a chemical model, the KARI‐catalyzed reaction has been demonstrated to include the initial deprotonation of the substrate C2 hydroxy group, bridged by the two Mg ions, alkyl migration from the C2‐alkoxide carbon atom to the C3‐carbonyl carbon atom, and hydride transfer from a nicotinamide adenine dinucleotide phosphate [NAD(P)H] cofactor to C2. A dead‐end mechanism with a hydride transferred to the C3 carbonyl group has been ruled out. The nucleophilicity (migratory aptitude) of the migrating carbon atom and the provision of additional negative charge to the di‐Mg coordination sphere have significant effects on the steps of alkyl migration and hydride transfer, respectively. Other important mechanistic characteristics are also revealed. Inspired by the mechanism, an inhibitor (2‐carboxylate‐lactic acid) was designed and predicted by barrier analysis to be effective in inactivating KARI, hence probably enriching the antifungal and antibacterial library. Two types of slow substrate analogues (2‐trihalomethyl acetolactic acids and 2‐glutaryl lactic acid) were also found.
Exotic Bonding Regimes Uncovered in Excited States
Authors: Casals‐Sainz José Luis , Jara‐Cortés Jesús , Hernández‐Trujillo Jesús , Guevara‐Vela José Manuel , Francisco Evelio , Pendás Ángel Martín 
Published: July 2019

AbstractReal‐space tools were employed to show that the chemical bonding scenario used routinely to understand ground states lacks the necessary flexibility in excited states. It is shown that, even for two‐center, two‐electron bonds, the real‐space bond orders have exotic values that have never been reported. The nature of these situations was uncovered by using electron‐counting techniques that provide an appealing statistical interpretation of bonding descriptors, together with simple physical models. Bond orders greater than one as well as negative bond orders for a single bonding electron pair emerge in situations in which the electrons in the pair show a gregarious (bosonic) instead of the usual lonely (fermionic) behavior. In the first case the gregarious pair is intra‐atomic, whereas the coupling is interatomic in the second. A number of examples are used to substantiate these claims.
Gold‐Catalyzed Regiospecific Annulation of Unsymmetrically Substituted 1,5‐Diynes for the Precise Synthesis of Bispentalenes
Authors: Tavakkolifard Sara , Sekine Kohei , Reichert Lisa , Ebrahimi Mina , Museridz Ketevan , Michel Elena , Rominger Frank , Babaahmadi Rasool , Ariafard Alireza , Yates Brian F. , Rudolph Matthias , Hashmi A. Stephen K. 
Published: July 2019

AbstractPrecise control of the selectivity in organic synthesis is important to access the desired molecules. We demonstrate a regiospecific annulation of unsymmetrically substituted 1,2‐di(arylethynyl)benzene derivatives for a geometry‐controlled synthesis of linear bispentalenes, which is one of the promising structures for material science. A gold‐catalyzed annulation of unsymmetrically substituted 1,2‐di(arylethynyl)benzene could produce two isomeric pentalenes, but both electronic and steric effects on the aromatics at the terminal position of the alkyne prove to be crucial for the selectivity; especially a regiospecific annulation was achieved with sterically blocked substituents; namely, 2,4,6‐trimetyl benzene or 2,4‐dimethyl benzene. This approach enables the geometrically controlled synthesis of linear bispentalenes from 1,2,4,5‐tetraethynylbenzene or 2,3,6,7‐tetraethynylnaphthalene. Moreover, the annulation of a series of tetraynes with a different substitution pattern regioselectively provided the bispentalene scaffolds. A computational study revealed that this is the result of a kinetic control induced by the bulky NHC ligands.
A Chemical Proteomic Analysis of Illudin‐Interacting Proteins
Authors: Le Philipp , Nodwell Matthew B. , Eirich Jürgen , Sieber Stephan A. 
Published: July 2019

AbstractThe illudin natural product family are fungal secondary metabolites with a characteristic spirocyclopropyl‐substituted fused 6,5‐bicyclic ring system. They have been extensively studied for their cytotoxicity in various tumor cell types, and semisynthetic derivatives with improved therapeutic characteristics have progressed to clinical trials. Although it is believed that this potent alkylating compound class acts mainly through DNA modification, little is known about its binding to protein sites in a cellular context. To reveal putative protein targets of the illudin family in live cancer cells, we employed a semisynthetic strategy to access a series of illudin‐based probes for activity‐based protein profiling (ABPP). While the probes largely retained potent cytotoxicity, proteomic profiling studies unraveled multiple protein hits, suggesting that illudins exert their mode of action not from addressing a specific protein target but rather from DNA modification and unselective protein binding.
Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review
Authors: Silva Guilherme Martins , Barcelos Mariana Pegrucci , Poiani João Gabriel Curtolo , Hage‐Melim Lorane Izabel da Silva , da Silva Carlos Henrique Tomich de Paula 
Published: July 2019

AbstractAmong neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β‐amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.
Gene expression correlates of facultative predation in the blow fly Chrysomya rufifacies (Diptera: Calliphoridae)
Authors: Pimsler Meaghan L. , Sze Sing‐Hoi , Saenz Sunday , Fu Shuhua , Tomberlin Jeffery K. , Tarone Aaron M. 
Published: July 2019

AbstractEffects of intraguild predation (IGP) on omnivores and detritivores are relatively understudied when compared to work on predator guilds. Functional genetic work in IGP is even more limited, but its application can help answer a range of questions related to ultimate and proximate causes of this behavior. Here, we integrate behavioral assays and transcriptomic analysis of facultative predation in a blow fly (Diptera: Calliphoridae) to evaluate the prevalence, effect, and correlated gene expression of facultative predation by the invasive species Chrysomya rufifacies. Field work observing donated human cadavers indicated facultative predation by C. rufifacies on the native blow fly Cochliomyia macellaria was rare under undisturbed conditions, owing in part to spatial segregation between species. Laboratory assays under conditions of starvation showed predation had a direct fitness benefit (i.e., survival) to the predator. As a genome is not available for C. rufifacies, a de novo transcriptome was developed and annotated using sequence similarity to Drosophila melanogaster. Under a variety of assembly parameters, several genes were identified as being differentially expressed between predators and nonpredators of this species, including genes involved in cell‐to‐cell signaling, osmotic regulation, starvation responses, and dopamine regulation. Results of this work were integrated to develop a model of the processes and genetic regulation controlling facultative predation.
When the “selfish herd” becomes the “frozen herd”: spatial dynamics and population persistence in a colonial seabird
Authors: McDowall Philip S. , Lynch Heather J. 
Published: July 2019

AbstractAggregations are common in ecological systems at a range of scales and may be driven by exogenous constraints such as environmental heterogeneity and resource availability or by “self‐organizing” interactions among individuals. One mechanism leading to self‐organized animal aggregations is captured by Hamilton's “selfish herd” hypothesis, which suggests that aggregations may be driven by an individual's effort to minimize their risk of predation by surrounding themselves with conspecifics. We demonstrate that aggregations observed in Adélie Penguin (Pygoscelis adeliae) colonies are a convolution of both self‐organized dynamics and external forcing arising from landscape terrain. In fluid, highly mobile aggregations, individuals are constantly moving in response to changing environmental conditions, the locations of predators, or the movements of conspecifics. However, when the ability to rearrange is limited and spatial reconfiguration occurs on slower time scales than changes in population size, systems may become trapped in suboptimal arrangements. We use simulated annealing to demonstrate that Adélie Penguin colonies are frozen in suboptimal spatial arrangements, and employ an individual‐based modeling approach to demonstrate that this suboptimal spatial configuration is driven by a convolution of nest site fidelity and stochastic events at the level of individual nests. The resulting spatial dynamics are responsible for a hysteretic response to long‐term changes in abundance. We find that declining abundance leads to fragmentation even in a homogeneous environment, which has population‐level consequences for reproductive success because predation is biased towards colony edges. Strong edge effects from heterogeneous predation coupled with fragmentation in response to population declines create a positive feedback cycle that can accelerate population decline. This work provides a mechanistic understanding of complex spatial structuring in penguin colonies, provides a link between current spatial patterning and past dynamics, and suggests the possibility of critical collapse in seabird populations.
The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics
Authors: McMurray John J.V. , DeMets David L. , Inzucchi Silvio E. , Køber Lars , Kosiborod Mikhail N. , Langkilde Anna Maria , Martinez Felipe A. , Bengtsson Olof , Ponikowski Piotr , Sabatine Marc S. , Sjöstrand Mikaela , Solomon Scott D. ,   on behalf of the DAPA‐HF Committees and Investigators
Published: July 2019

BackgroundThe aims of this study were to: (i) report the baseline characteristics of patients enrolled in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial, (ii) compare DAPA‐HF patients to participants in contemporary heart failure (HF) registries and in other recent HF trials, and (iii) compare individuals with diabetes, pre‐diabetes and a normal glycated haemoglobin (HbA1c) in DAPA‐HF.Methods and resultsAdults with HF in New York Heart Association functional class ≥ II, a left ventricular ejection fraction ≤ 40%, an elevated N‐terminal pro‐B‐type natriuretic peptide concentration and receiving standard treatment were eligible for DAPA‐HF, which is comparing dapagliflozin 10 mg once daily to matching placebo. In patients without a history of diabetes, previously undiagnosed diabetes was defined as a confirmed HbA1c ≥ 6.5%. Among patients without known or undiagnosed diabetes, pre‐diabetes was defined as a HbA1c ≥ 5.7% The remainder of patients, with a HbA1c < 5.7%, were defined as normoglycaemic. Of the 4744 patients (mean age 66 years; 23% women) randomized, 42% had known diabetes and 3% undiagnosed diabetes. Of the remainder, 67% had pre‐diabetes and 33% normal HbA1c. Overall, DAPA‐HF patients were generally similar to those in recent registries and in relevant trials and had high levels of background therapy: 94% angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor, 96% beta‐blocker, and 71% mineralocorticoid receptor antagonist; 26% had a defibrillator. Patients with diabetes had worse HF status, more co‐morbidity, and greater renal impairment but received similar HF therapy. Patients with diabetes received non‐insulin hypoglycaemic therapy alone in 49%, insulin alone in 11%, both in 14%, and none in 26%.ConclusionsPatients randomized in DAPA‐HF were similar to those in other contemporary HF with reduced ejection fraction (HFrEF) registries and trials. These patients were receiving recommended HFrEF therapy and those with diabetes were also treated with conventional glucose‐lowering therapy. Consequently, DAPA‐HF will test the incremental efficacy and safety of dapagliflozin in HFrEF patients with and without diabetes.Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03036124