bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finite‐frequency wave propagation through outer rise fault zones and seismic measurements of upper mantle hydration
Authors: Miller Nathaniel C. , Lizarralde Daniel 
Published: August 2016

AbstractEffects of serpentine‐filled fault zones on seismic wave propagation in the upper mantle at the outer rise of subduction zones are evaluated using acoustic wave propagation models. Modeled wave speeds depend on azimuth, with slowest speeds in the fault‐normal direction. Propagation is fastest along faults, but, for fault widths on the order of the seismic wavelength, apparent wave speeds in this direction depend on frequency. For the 5–12 Hz Pn arrivals used in tomographic studies, joint‐parallel wavefronts are slowed by joints. This delay can account for the slowing seen in tomographic images of the outer rise upper mantle. At the Middle America Trench, confining serpentine to fault zones, as opposed to a uniform distribution, reduces estimates of bulk upper mantle hydration from ~3.5 wt % to as low as 0.33 wt % H2O.
A probabilistic prediction network for hydrological drought identification and environmental flow assessment
Authors: Liu Zhiyong , Törnros Tobias , Menzel Lucas 
Published: August 2016

AbstractA general probabilistic prediction network is proposed for hydrological drought examination and environmental flow assessment. This network consists of three major components. First, we present the joint streamflow drought indicator (JSDI) to describe the hydrological dryness/wetness conditions. The JSDI is established based on a high‐dimensional multivariate probabilistic model. In the second part, a drought‐based environmental flow assessment method is introduced, which provides dynamic risk‐based information about how much flow (the environmental flow target) is required for drought recovery and its likelihood under different hydrological drought initial situations. The final part involves estimating the conditional probability of achieving the required environmental flow under different precipitation scenarios according to the joint dependence structure between streamflow and precipitation. Three watersheds from different countries (Germany, China, and the United States) with varying sizes from small to large were used to examine the usefulness of this network. The results show that the JSDI can provide an assessment of overall hydrological dryness/wetness conditions and performs well in identifying both drought onset and persistence. This network also allows quantitative prediction of targeted environmental flow required for hydrological drought recovery and estimation of the corresponding likelihood. Moreover, the results confirm that the general network can estimate the conditional probability associated with the required flow under different precipitation scenarios. The presented methodology offers a promising tool for water supply planning and management and for drought‐based environmental flow assessment. The network has no restrictions that would prevent it from being applied to other basins worldwide.
D
iamond–
B
lackfan Anaemia: From Genotype to Phenotype
Authors: Paolini Nahuel A , MacInnes Alyson W , von Lindern Marieke 
Published: August 2016

Abstract

Diamond–Blackfan anaemia (DBA) is a congenital disorder that presents in the first year of life as severe anaemia, and in several patients is coupled with developmental defects. DBA is a ribosomopathy because almost all known mutations or deletions occur in genes encoding ribosomal proteins (RPs) that impair ribosome biogenesis. However, atypical examples of patients carry mutations in the erythroid specific transcription factor GATA1. DBA is a rare disease that displays a high level of heterogeneity with respect to the affected RP and disease penetrance. The reduced availability of ribosomes affects several cellular processes, including stabilisation of the p53 tumour suppressor, and impaired messenger ribonucleic acid (mRNA) translation. Registration of the genetic and phenotypic characteristics of DBA patients worldwide is needed to understand the relation between mutations, patient symptoms and cellular processes that underlie this pathophysiology.

Key Concepts

Diamond–Blackfan anaemia (DBA) is caused by haploinsufficiency of one of several ribosomal proteins in at least two‐thirds of all patients; the disease causing mutation is unknown in approximately 30% of patients.

The mechanisms underlying the ribosomopathy DBA are multiple, and are incompletely understood.

Particularly, the roles of transcript specific translation and iron homeostasis are underestimated.

Defective mRNA translation in ribosomopathies such as DBA should be investigated in cells that are affected in the disease, because an mRNA translation defect depends on the cell's specific transcriptome.

DBA type I and DBA type II should be used to distinguish between patients carrying
RP
mutations versus those carrying mutations in genes that specifically affect erythropoiesis including
GATA1
.

The ribosomopathy Diamond–Blackfan anaemia should be renamed to Diamond–Blackfan syndrome to emphasise that it is a systemic disease of which severe anaemia at young age is the most common, but not the exclusive symptom.

The heterogeneity with which DBA presents, even when family members carry the same mutation, needs to be investigated to find a proper treatment for severe DBA.
The Concept of ‘
G
aia’
Authors: Attfield Robin , Attfield Kate 
Published: August 2016

Abstract

The Gaia theory of James Lovelock proposes that the Earth is a self‐regulating system, or super‐organism, maintaining conditions hospitable to contemporary planetary biota. Objections to this theory, concerning its alleged untestability and circularity, are considered and countered. Favourable evidence includes Lovelock's Daisyworld model of a planet regulating its own temperatures and thus maintaining homeostasis, and his discoveries of actual regulatory mechanisms such as the biological generation of dimethyl sulphide, which removes sulfur from the oceans and seeds clouds whose albedo reduces solar radiation (a negative feedback mechanism). After some decades of scepticism, sections of the scientific community have partially endorsed Gaia theory, accepting that the Earth system behaves as if self‐regulating. Whether or not this theory is acceptable in full, it has drawn attention to the need for preserving planetary biological cycles and for the planetary dimension to be incorporated in ethical decision‐making, and thus for a planetary ethic.

Key Concepts

James Lovelock hypothesises that the planetary physical and biological system is a self‐regulating super‐organism.

There were precedents before Lovelock for ascribing life either to the planet or to the universe.

James W. Kirchner presents Gaia hypotheses as either unoriginal or untestable.

Lovelock demonstrates that Gaia theory is both original and testable, albeit indirectly.

Lovelock's theory can readily escape the charge of circularity.

Predictions of Gaia theory include the existence of biologically generated mechanisms of planetary regulation.

Lovelock's discovery of dimethyl sulphide discloses such a mechanism for the regulation of oceanic sulfur.

Both atmospheric oxygen and atmospheric nitrogen turn out to be biologically generated and maintained.

Philosophers such as Stephen Clark and Mary Midgley have made Gaia a symbol for the planetary thinking currently needed.

The Amsterdam Declaration of planetary scientists (Moore
et al
., 2001) accepted aspects of Gaia theory, without explicitly accepting the theory's planetary goal.
Human Topoisomerase
I
Inhibitors
Authors: Desideri Alessandro 
Published: August 2016

Abstract

Topoisomerases are ubiquitous enzymes that solve topological problems due to DNA (deoxyribonucleic acid) supercoiling occurring during the replication, transcription, recombination and chromatin remodelling processes. Human topoisomerase IB (Topo IB) is the selective target of camptothecin, a natural compound from which two powerful anticancer drugs, topotecan and irinotecan, are produced. Camptothecin acts as an interfacial inhibitor interacting with both the enzyme and DNA stabilising the covalent enzyme–DNA complex, and slowing down the religation of the broken DNA strands brings cells to death. Topo IB is also important for transcription of genes involved in neurodevelopment, and its inhibition during critical stages of brain development may be responsible for neurodevelopmental disorders.

Key Concepts

Topoisomerases are crucial enzymes essential in the relaxation of supercoiled DNA.

Human topoisomerase IB cuts a single DNA strand forming a transient enzyme–DNA cleavage complex.

Camptothecin is a natural compound of which human topoisomerase IB is the only cellular target.

Camptothecin can trap the enzyme–DNA cleavage complex bringing cells to death.

Two camptothecin derivatives have been approved by the US Food and Drug Administration: topotecan for ovarian and lung cancers and irinotecan for colorectal cancer.

Camptothecin and its derivatives act as interfacial inhibitors interacting with both the enzyme and the DNA.

Single topoisomerase mutation may induce resistance to camptothecin.

New non‐camptothecin derivatives are under development.

The cytotoxic activity of camptothecin increases in the presence of other compounds inhibiting enzymes involved in DNA repair.

Inhibition of topoisomerase IB has also a strong influence on the modulation expression of groups of genes associated with autism.
Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment
Authors: Gertz Morie A. 
Published: August 2016

Disease OverviewImmunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma.DiagnosisTissue biopsy stained with Congo red demonstrating amyloid deposits with applegreen birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory.PrognosisN‐terminal pro–brain natriuretic peptide (NTproBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months.TherapyAll patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mmHg, troponin T <0.06 ng mL21, age <70 years, and serum creatinine 1.7 mg dL21. Nontransplant candidates can be offered melphalan‐dexamethasone or cyclophosphamide‐bortezomib‐dexamethasone. Other combinations of chemotherapy with agents such as cyclophosphamide‐thalidomide (or lenalidomide)‐dexamethasone, bortezomib‐dexamethasone, and melphalan‐prednisone‐lenalidomide have documented activity. Antibodies designed to dissolve existing amyloid deposits are under study for previously treated and untreated patients. Late diagnosis remains a major obstacle to initiating effective therapy. Am. J. Hematol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hematol. 91:948–956, 2016. © 2016 Wiley Periodicals, Inc.
Tunable Nanosupramolecular Aggregates Mediated by Host–Guest Complexation
Authors: Zhang Wen , Zhang Ying‐Ming , Li Sheng‐Hua , Cui Yong‐Liang , Yu Jie , Liu Yu 
Published: August 2016

AbstractNanosupramolecular assemblies with controlled topological features have inventive applications in fundamental studies and material manufacturing. Herein, a variety of morphologically interesting aggregates have been constructed using the supramolecular modulation with bipyridinium‐modified diphenylalanine derivative (BP‐FF). Benefiting from the high binding affinity of bipyridinium group with four different macrocyclic receptors, namely cucurbit[7]uril, cucurbit[8]uril, pillar[5]arene, and tetrasulfonated crown ether, we have succeeded in tuning the topological aggregates of BP‐FF from fine nanofibers to nanorods, octahedron‐like nanostructure, helical nanowires, and rectangular nanosheets without any tedious chemical modification. This supramolecular approach may provide us a powerful method to construct well‐defined nanostructures with different morphologies that can be conveniently controlled by facile host–guest interactions.
Enhancing the Sensitivity of CPMG Relaxation Dispersion to Conformational Exchange Processes by Multiple‐Quantum Spectroscopy
Authors: Yuwen Tairan , Vallurupalli Pramodh , Kay Lewis E. 
Published: August 2016

AbstractA triple‐quantum 1H Carr–Purcell–Meiboom–Gill NMR relaxation dispersion experiment is presented that uses methyl group probes as reporters of conformational exchange in highly deuterated, methyl‐protonated proteins. Significantly larger dispersion profiles, by as much as a factor of nine, can be obtained relative to single‐quantum approaches, thus offering very significant advantages in applications involving interconverting conformers with only small changes in structure or in studies of rare states that are at very low populations. Applications to a number of protein systems are presented where the utility of the method, including its improved sensitivity to chemical exchange processes, is established.
Hydrolysis of polylactide in aqueous media
Authors: Rodriguez Edwin J. , Marcos Bernard , Huneault Michel A. 
Published: August 2016

ABSTRACTIn this study, two commercial polylactide (PLA) grades with different d‐lactate contents were subjected to hydrolysis in neutral, acidic, and alkaline aqueous media at temperatures above the glass transition. We monitored the hydrolysis process by means of tracking the changes in the molecular weight distribution, weight loss, water uptake, and PLA crystallinity as a function of time. In both, neutral and acidic media, hydrolysis showed an initial induction period over which no weight loss was observed, whereas the average molecular weight dropped drastically. After this initial period, the weight loss increased rapidly, whereas the molecular weight decreased slowly. Additionally, in alkaline media, hydrolysis occurred mainly through a surface‐erosion process; this resulted in a simultaneous molecular weight decrease and weight loss without a noticeable induction period. An autocatalytic mechanism was assumed in neutral and acidic media to describe the hydrolysis kinetics. The measured molecular weight decrease over time was successfully described by a two‐stage exponential model. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44152.
meso‐Nitro‐ and meso‐Aminosubporphyrinatoboron(III)s and meso‐to‐meso Azosubporphyrinatoboron(III)s
Authors: Shimizu Daiki , Lee Seung‐Kyu , Kim Dongho , Osuka Atsuhiro 
Published: August 2016

Abstractmeso‐Nitrosubporphyrinatoboron(III) was synthesized by nitration of meso‐free subporphyrin with AgNO2/I2. The subsequent reduction with a combination of NaBH4 and Pd/C gave meso‐aminosubporphyrinatoboron(III). meso‐Nitro‐ and meso‐amino‐groups significantly influenced the electronic properties of subporphyrin, which has been confirmed by NMR and UV/Vis spectra, electrochemical analysis, and DFT calculations. Oxidation of meso‐aminosubporphyrinatoboron(III)s with PbO2 cleanly gave meso‐to‐meso azosubporphyrinatoboron(III)s that exhibited almost coplanar conformations and large electronic interaction through the azo‐bridge.
High throughput, colorimetric screening of microbial ester biosynthesis reveals high ethyl acetate production from Kluyveromyces marxianus on C5, C6, and C12 carbon sources
Authors: Löbs Ann‐Kathrin , Lin Jyun‐Liang , Cook Megan , Wheeldon Ian 
Published: August 2016

AbstractAdvances in genome and metabolic pathway engineering have enabled large combinatorial libraries of mutant microbial hosts for chemical biosynthesis. Despite these advances, strain development is often limited by the lack of high throughput functional assays for effective library screening. Recent synthetic biology efforts have engineered microbes that synthesize acetyl and acyl esters and many yeasts naturally produce esters to significant titers. Short and medium chain volatile esters have value as fragrance and flavor compounds, while long chain acyl esters are potential replacements for diesel fuel. Here, we developed a biotechnology method for the rapid screening of microbial ester biosynthesis. Using a colorimetric reaction scheme, esters extracted from fermentation broth were quantitatively converted to a ferric hydroxamate complex with strong absorbance at 520 nm. The assay was validated for ethyl acetate, ethyl butyrate, isoamyl acetate, ethyl hexanoate, and ethyl octanoate, and achieved a z‐factor of 0.77. Screening of ethyl acetate production from a combinatorial library of four Kluyveromyces marxianus strains on seven carbon sources revealed ethyl acetate biosynthesis from C5, C6, and C12 sugars. This newly adapted method rapidly identified novel properties of K. marxianus metabolism and promises to advance high throughput microbial strain engineering for ester biosynthesis.
A thioacidolysis method tailored for higher‐throughput quantitative analysis of lignin monomers
Authors: Harman‐Ware Anne E. , Foster Cliff , Happs Renee M. , Doeppke Crissa , Meunier Kristoffer , Gehan Jackson , Yue Fengxia , Lu Fachuang , Davis Mark F. 
Published: August 2016

AbstractThioacidolysis is a method used to measure the relative content of lignin monomers bound by β‐O‐4 linkages. Current thioacidolysis methods are low‐throughput as they require tedious steps for reaction product concentration prior to analysis using standard GC methods. A quantitative thioacidolysis method that is accessible with general laboratory equipment and uses a non‐chlorinated organic solvent and is tailored for higher‐throughput analysis is reported. The method utilizes lignin arylglycerol monomer standards for calibration, requires 1–2 mg of biomass per assay and has been quantified using fast‐GC techniques including a Low Thermal Mass Modular Accelerated Column Heater (LTM MACH). Cumbersome steps, including standard purification, sample concentrating and drying have been eliminated to help aid in consecutive day‐to‐day analyses needed to sustain a high sample throughput for large screening experiments without the loss of quantitation accuracy. The method reported in this manuscript has been quantitatively validated against a commonly used thioacidolysis method and across two different research sites with three common biomass varieties to represent hardwoods, softwoods, and grasses.
Myosin light chain kinase steady‐state kinetics: comparison of smooth muscle myosin II and nonmuscle myosin IIB as substrates
Authors: Alcala Diego B. , Haldeman Brian D. , Brizendine Richard K. , Krenc Agata K. , Baker Josh E. , Rock Ronald S. , Cremo Christine R. 
Published: August 2016

Myosin light chain kinase (MLCK) phosphorylates S19 of the myosin regulatory light chain (RLC), which is required to activate myosin's ATPase activity and contraction. Smooth muscles are known to display plasticity in response to factors such as inflammation, developmental stage, or stress, which lead to differential expression of nonmuscle and smooth muscle isoforms. Here, we compare steady‐state kinetics parameters for phosphorylation of different MLCK substrates: (1) nonmuscle RLC, (2) smooth muscle RLC, and heavy meromyosin subfragments of (3) nonmuscle myosin IIB, and (4) smooth muscle myosin II. We show that MLCK has a ~2‐fold higher kcat for both smooth muscle myosin II substrates compared with nonmuscle myosin IIB substrates, whereas Km values were very similar. Myosin light chain kinase has a 1.6‐fold and 1.5‐fold higher specificity (kcat/Km) for smooth versus nonmuscle‐free RLC and heavy meromyosin, respectively, suggesting that differences in specificity are dictated by RLC sequences. Of the 10 non‐identical RLC residues, we ruled out 7 as possible underlying causes of different MLCK kinetics. The remaining 3 residues were found to be surface exposed in the N‐terminal half of the RLC, consistent with their importance in substrate recognition. These data are consistent with prior deletion/chimera studies and significantly add to understanding of MLCK myosin interactions.Significance of the studyPhosphorylation of nonmuscle and smooth muscle myosin by myosin light chain kinase (MLCK) is required for activation of myosin's ATPase activity. In smooth muscles, nonmuscle myosin coexists with smooth muscle myosin, but the two myosins have very different chemo‐mechanical properties relating to their ability to maintain force. Differences in specificity of MLCK for different myosin isoforms had not been previously investigated. We show that the MLCK prefers smooth muscle myosin by a significant factor. These data suggest that nonmuscle myosin is phosphorylated more slowly than smooth muscle myosin during a contraction cycle.
Cost‐effectiveness of percutaneous coronary intervention with cobalt‐chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta‐analysis of randomized trials
Authors: Ferko Nicole , Ferrante Giuseppe , Hasegawa James T. , Schikorr Tanya , Soleas Ireena M. , Hernandez John B. , Sabaté Manel , Kaiser Christoph , Brugaletta Salvatore , de la Torre Hernandez Jose Maria , Galatius Soeren , Cequier Angel , Eberli Franz , de Belder Adam , Serruys Patrick W. , Valgimigli Marco 
Published: August 2016

BackgroundSecond‐generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first‐generation DES with improved cost‐effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt‐chromium everolimus eluting stent (Co‐Cr EES) compared with BMS in percutaneous coronary intervention (PCI).ObjectiveTo conduct a cost‐effectiveness analysis (CEA) of a cobalt‐chromium everolimus eluting stent (Co‐Cr EES) versus BMS in PCI.MethodsA Markov state transition model with a 2‐year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co‐Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta‐analysis of 5 RCTs (n = 4,896). The base‐case analysis evaluated stent‐related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta‐analysis.ResultsThe base‐case and secondary analyses reported an additional 0.018 and 0.013 quality‐adjusted life years (QALYs) and cost savings of $236 and $288, respectively with Co‐Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co‐Cr EES was associated with a greater than 99% chance of being cost saving or cost effective (at a cost per QALY threshold of $50,000) versus BMS.ConclusionsUsing data from a recent patient level meta‐analysis and contemporary cost data, this analysis found that PCI with Co‐Cr EES is more effective and less costly than PCI with BMS. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.