bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Study of Self‐Assembled Superstructures from Cellulose Stearoyl Ester and Poly(Vinyl Stearate)
Authors: Wang Yonggui , Zhang Chi , Tian Jia , Xie Yanjun , Zhang Kai 
Published: August 2018

AbstractComb‐like cellulose stearoyl ester (CSE3) and poly(vinyl stearate) (PVS) with distinct skeletons are successfully synthesized. Their self‐assembled superstructures are described and discussed comparatively herein. Differential scanning calorimetry investigation indicates that both comb‐like polymers with various molecular weights show the feasibility to form self‐assembled crystalline structures. The self‐assembled superstructures are obtained from both the evaporation‐induced and temperature‐induced phase separation processes. Due to the interference of different skeletons, self‐assembled superstructures of both comb‐like polymers demonstrate totally different morphologies. CSE3 with semi‐flexible skeleton forms robust petals, which further grows into well‐organized flower‐like particles. In contrast, PVS with more flexible skeleton only form non‐ordered porous structures through stacking of the wrinkled and folded nanofilms.
Continuous DNA Nanofibers with Extraordinary Mechanical Properties and High Molecular Orientation
Authors: Maleckis Kaspars , Dzenis Yuris 
Published: August 2018

AbstractThe dual nano–macro nature of continuous nanofibers holds great promise in bridging the unique nanoscale properties of DNA to macroscopic devices. However, due to the limitations of existing manufacturing methods, controlled fabrication of macroscopically long DNA nanofibers has not been achieved so far. This article presents optimized electrospinning of substrate‐free and uniform DNA nanofibers with macroscopic lengths and diameters ranging from ultrafine (<50 nm) to submicron scale. Mechanical tests of individual DNA nanofibers show highly nonlinear deformation in tension that is accompanied by unexpectedly high true strength (>1 GPa) and toughness (>200 MPa) values for the thinnest tested nanofibers. Molecular characterization with X‐ray diffraction and polarized Raman spectroscopy indicates that the high mechanical properties and their unusual size effects in DNA nanofibers originate from the high molecular alignment that is preserved with the increase in diameter. These results show that electrospun DNA nanofibers can overcome the weaknesses of DNA nanostructures manufactured by other top‐down and bottom‐up methods and that they offer novel capabilities for the DNA‐based nanomaterials.
Building Micelle Analog Nanoparticle for Multidrug Delivery: Dual‐Polymer Nanoparticles with Hydrophilic Shell and Double Hydrophobic Layers
Authors: Wu Zhengzhong , Liu Yanjun , Cao Jun , Huang Lei , Luo Xianglin 
Published: August 2018

AbstractMultidrug delivery systems are capturing much attention while ingenious drug carriers are drug delivery researchers' pursuit. A method building dual‐polymer nanoparticles (DPNs), one analogous micelle nanoparticle, with double hydrophobic core layers and a hydrophilic shell, is developed by combining co‐axial injection and solvent evaporation using a hydrophobic and an amphiphilic polymer. Hydrophobic drugs can be efficiently and zonally encapsulated in core and/or outer hydrophobic zone of DPN. As a result, DPN can sequentially release drugs and appears stronger growth inhibition to Hela cells and cell uptake than normal drug‐loaded micelles. Moreover, this method is universal to other material combinations of hydrophobic/amphiphilic polymers. Therefore, DPN has potential as one multidrug delivery system.
Synthesis of Single‐Ring Nanoparticles Mimicking Natural Cyclotides by a Stepwise Folding‐Activation‐Collapse Process
Authors: Rubio‐Cervilla Jon , Frisch Hendrik , Barner‐Kowollik Christopher , Pomposo José A. 
Published: August 2018

AbstractCyclotides are small cyclic polypeptides found in a variety of organisms, ranging from bacteria to plants. Their ring structure endows those polypeptides with specific properties, such as improved stability against enzymatic degradation. Optimal cyclotide activity is often observed only in the presence of intra‐ring disulfide bonds. Synthesis of soft nano‐objects mimicking the conformation of natural cyclotides remains challenging. Here, a new class of natural cyclotide mimics synthesized by a stepwise folding‐activation‐collapse process at high dilution starting from simple synthetic precursor polymers is established. The initial folding step is carried out by a photoactivated hetero Diels–Alder (HDA) ring‐closing reaction, which is accompanied by chain compaction of the individual precursor polymer chains as determined by size exclusion chromatography (SEC). The subsequent activation step comprises a simple azidation procedure, whereas the final collapse step is driven by CuAAC in the presence of an external cross‐linker, providing additional compaction to the final single‐ring nanoparticles (SRNPs). The unique structure and compaction degree of the SRNPs is established via a detailed comparison with conventional single‐chain nanoparticles (SCNPs) prepared exclusively by chain collapse from the exact same precursor polymer (without the prefolding step). The stepwise folding‐activation‐collapse approach opens new avenues for the preparation of artificial cyclotide mimetics.
Optimized in vivo brain glutamate measurement using long‐echo‐time semi‐LASER at 7 T
Authors: Wong Dickson , Schranz Amy L. , Bartha Robert 
Published: August 2018

A short echo time (TE) is commonly used for brain glutamate measurement by 1H MRS to minimize drawbacks of long TE such as signal modulation due to J evolution and T2 relaxation. However, J coupling causes the spectral patterns of glutamate to change with TE, and the shortest achievable TE may not produce the optimal glutamate measurement. The purpose of this study was to determine the optimal TE for glutamate measurement at 7 T using semi‐LASER (localization by adiabatic selective refocusing). Time‐domain simulations were performed to model the TE dependence of glutamate signal energy, a measure of glutamate signal strength, and were verified against measurements made in the human sensorimotor cortex (five subjects, 2 × 2 × 2 cm3 voxel, 16 averages) on a 7 T MRI scanner. Simulations showed a local maximum of glutamate signal energy at TE = 107 ms. In vivo, TE = 105 ms produced a low Cramér‐Rao lower bound of 6.5 ± 2.0% across subjects, indicating high‐quality fits of the prior knowledge model to in vivo data. TE = 105 ms also produced the greatest glutamate signal energy with the smallest inter‐subject glutamate‐to‐creatine ratio (Glu/Cr) coefficient of variation (CV), 4.6%. Using these CVs, we performed sample size calculations to estimate the number of participants per group required to detect a 10% change in Glu/Cr between two groups with 95% confidence. 13 were required at TE = 45 ms, the shortest achievable echo time on our 7 T MRI scanner, while only 5 were required at TE = 105 ms, indicating greater statistical power. These results indicate that TE = 105 ms is optimum for in vivo glutamate measurement at 7 T with semi‐LASER. Using long TE decreases power deposition by allowing lower maximum RF pulse amplitudes in conjunction with longer RF pulses. Importantly, long TE minimizes macromolecule contributions, eliminating the requirement for acquisition of separate macromolecule spectra or macromolecule fitting techniques, which add additional scan time or bias the estimated glutamate fit.
Solid‐phase synthesis of peptide β‐aminoboronic acids
Authors: Soor Harjeet S. , Hansen Jonas , Diaz Diego B. , Appavoo Solomon , Yudin Andrei K. 
Published: August 2018

AbstractPeptide/boronic acid conjugates are attractive scaffolds for chemical probe discovery and drug design. There are only a few reactions that allow for rapid incorporation of boron into peptides. Herein, we report a new approach towards the synthesis of peptide β‐aminoboronic acids on solid support using 2‐chlorotrityl resin and solid‐phase peptide synthesis techniques with only one purification required. Evaluation of model compounds demonstrate the stability of peptide boronic acids toward degradation at physiological pH. This straightforward conjugation process should allow access to a wide range of peptide boronic acid scaffolds for both synthetic and medicinal use.
Investigating the Potential for Bias When Using a Widely Accepted Medication Adherence Measure to Predict Mortality
Authors: Ward Ralph C. , Taber David J. , Axon Robert Neal , Gebregziabher Mulugeta 
Published: August 2018

Study ObjectiveSummary measures of medication adherence, such as the proportion of days covered (PDC), are often used to analyze the association between medication adherence and various health outcomes. We hypothesized that PDC and similar measures may lead to biased results in some situations when used to estimate the association between adherence and the outcome event (e.g., mortality). Thus, the objective was to determine the conditions under which PDC and similar measures might produce biased estimates of the association between adherence and mortality and to review methods to avoid such bias.DesignSimulation study and analysis of data from a large retrospective cohort study.Measurements and Main ResultsWe conducted a comprehensive simulation to compare how adherence estimates varied—using prescription‐based (end point was final date that medications were on hand or date of death) and interval‐based (end point based on fixed calendar interval or date of death) PDC denominators—when deaths occurred either during or after the adherence exposure period. We then made similar comparisons using data from a retrospective study that included comprehensive measures of medication refill activity and clinical outcomes of 207,841 patients with diabetes mellitus who were prescribed one or more oral antidiabetic medications. When deaths occurred within the adherence exposure period, substantial bias in adherence estimates was possible regardless of the PDC denominator type.ConclusionInvestigators using PDC or similar proxy measures should carefully consider the temporal relationship between adherence exposure and clinical outcomes when the outcome event affects the adherence measurement.
The Microstructure, Proteomics and Crystallization of the Limpet Teeth
Authors: Wang Yadong , Liu Chuang , Du Jinzhe , Huang Jingliang , Zhang Shuce , Zhang Rongqing 
Published: August 2018

AbstractLimpets are marine mollusks that use mineralized teeth, one of the hardest and strongest biomaterials, to feed on algae on intertidal rocks. However, most of studies only focus on the ultrastructure and chemical composition of the teeth while the molecular information is largely unknown, limiting our understanding of this unique and fundamental biomineralization process. The study investigates the microstructure, proteomics, and crystallization in the teeth of limpet Cellana toreuma. It is found that the limpets formed alternatively tricuspid teeth and unicuspid teeth. Small nanoneedles are densely packed at the tips or leading regions of the cusps. In contrast, big nanoneedles resembling chemically synthesized goethite are loosely packed in the trailing regions of the cusps. Proteins extracted from the whole radula, such as ferritin, peroxiredoxin, arginine kinase, GTPase‐Rabs, and clathrin, are identified by proteomics. A goethite‐binding experiment coupled with proteomics and RNA‐seq highlights six chitin‐binding proteins (CtCBPs). Furthermore, the extracted proteins from the cusps of radula or the framework chitin induce packing of crystals and possibly affect crystal polymorphs in vitro. This study provides insight into the unique biomineralization process in the limpet teeth at the molecular levels, which may guide biomimetic strategies aimed at designing hard materials at room temperature.
Single/Dual Alkaline Earth Metal‐Doped Hollow Nanoparticles as Nanocarrier for Accelerating Neurite Development by Activating pERK and pJNK
Authors: Jang Yoonsun , Yoon Chang‐Min , Kim Sojin , Lee Inkyu , Jang Jyongsik 
Published: August 2018

AbstractNeuronal differentiation promoted by protein delivery is a promising strategy for the treatment of neuropathies. Herein, alkaline earth metal (AEM)‐doped hollow nanoparticles (HNPs) are utilized for simultaneous delivery of metal ions and nerve growth factor (NGF) toward cell interiors via endocytosis. Various AEMs including Mg, Ca, Sr, and Ba are readily doped onto the HNPs and the resulting AEM‐HNPs serve as NGF delivery agents. Benefiting from the hollow morphology, NGFs are successfully loaded into AEM‐HNPs to obtain NGF‐loaded N+AEM‐HNPs. These are applied as neuronal development agents for PC12 cells, a model for neuronal development experiments. The neuronal development efficiency of PC12 is improved in the presence of all N+AEM‐HNPs. Notably, the AEM‐HNPs manifest neuronal development effects that depend on the identity of the AEMs. Specifically, by studying the protein expressions and their signal transduction pathways, it is found that PC12 cells are activated by different signaling cascades according to each AEM ions. Additionally, Mg/Sr‐HNPs containing both Mg2+ and Sr2+ ions are prepared to examine the effect of dual stimulation of AEM ions on PC12 cells. This novel dual‐delivery system provides new insights into the synergistic neuronal development effect of AEM ions and protein in a single system.
Structural metamorphism and polymorphism in proteins on the brink of thermodynamic stability
Authors: Kulkarni Prakash , Solomon Tsega L. , He Yanan , Chen Yihong , Bryan Philip N. , Orban John 
Published: August 2018

AbstractThe classical view of the structure–function paradigm advanced by Anfinsen in the 1960s is that a protein's function is inextricably linked to its three‐dimensional structure and is encrypted in its amino acid sequence. However, it is now known that a significant fraction of the proteome consists of intrinsically disordered proteins (IDPs). These proteins populate a polymorphic ensemble of conformations rather than a unique structure but are still capable of performing biological functions. At the boundary, between well‐ordered and inherently disordered states are proteins that are on the brink of stability, either weakly stable ordered systems or disordered but on the verge of being stable. In such marginal states, even relatively minor changes can significantly alter the energy landscape, leading to large‐scale conformational remodeling. Some proteins on the edge of stability are metamorphic, with the capacity to switch from one fold topology to another in response to an environmental trigger (e.g., pH, temperature/salt, redox). Many IDPs, on the other hand, are marginally unstable such that small perturbations (e.g., phosphorylation, ligands) tip the balance over to a range of ordered, partially ordered, or even more disordered states. In general, the structural transitions described by metamorphic fold switches and polymorphic IDPs possess a number of common features including low or diminished stability, large‐scale conformational changes, critical disordered regions, latent or attenuated binding sites, and expansion of function. We suggest that these transitions are, therefore, conceptually and mechanistically analogous, representing adjacent regions in the continuum of order/disorder transitions.
Standardization of CTC AR‐V7 PCR assay and evaluation of its role in castration resistant prostate cancer progression
Authors: Tommasi Stefania , Pilato Brunella , Carella Claudia , Lasorella Antonia , Danza Katia , Vallini Ivan , De Summa Simona , Naglieri Emanuele 
Published: August 2018

BackgroundCastration resistant prostate cancer (CRPC) represents the most aggressive status of this neoplastic disease, also characterized by the absence of biomarkers predictive of clinical outcome. New drugs as abiraterone or enzalutamide, affecting androgen receptor pathway at different levels, inhibit the proliferative advantage of prostate cancer cells with important long term benefits. Despite the advantages of this second‐generation androgen deprivation therapy (ADT), resistance mechanisms, primitive or acquired, often develop. The existence of androgen receptor (AR) splice variants (AR‐Vs), in particular AR‐V7 expression detected in circulating tumor cells (CTCs), represents an example of acquired resistance, as evidenced in preclinical and clinical studies. Recent studies also have suggested the role of AR‐V7 as a prognostic biomarker in mCRPC. In this field, hot topics are the methodology used to isolate CTC and the assay for AR‐V7 measurement. Our study aims to develop a standardized operating procedure (SOP) to evaluate AR‐V7 in CRPC.MethodThe application of a realized cell based Reference Sample as Standardized Quality Control tool for CTC‐AR‐V7 assay has been shown. Then the development, the performance evaluation and contextualization in a clinical setting of this standardized operating procedure (SOP) have been reported to evaluate the prognostic biomarker AR‐V7 in metastatic prostate cancer.Results and ConclusionsThe standardized procedure has high sensitivity and specificity and enables the detection and quantification of the spliced variant with respect to the full length AR (AR‐FL) mRNA in CTC DNA purified from the blood of patients with CRPC. This procedure has been further validated in a consecutive series of patients with mCRPC, confirming its role as prognostic biomarker.
Association of genetic variation of the six gene prognostic model for castration‐resistant prostate cancer with survival
Authors: Xie Wanling , Stopsack Konrad H. , Drouin Sarah J. , Fu Henry , Pomerantz Mark M. , Mucci Lorelei A. , Lee Gwo‐Shu M. , Kantoff Philip W. 
Published: August 2018

BackgroundWe previously identified a blood RNA transcript‐based model consisting of six immune or inflammatory response genes (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that was prognostic for survival in cohorts of men with castration‐resistant prostate cancer (CRPC). We investigated whether inherited variation in these six genes was associated with overall survival (OS) in men with CRPC.MethodsThe test cohort comprised 600 patients diagnosed with CRPC between 1996 and 2011 at Dana‐Farber Cancer Institute. Genotyping of 66 tagging single nucleotide polymorphisms (SNPs) spanning the six genes was performed on blood derived DNAs. For the top four SNPs (P < 0.05), validation was conducted in an independent cohort of 223 men diagnosed with CRPC between 2000 and 2014. Multivariable Cox regression adjusting for known prognostic factors estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association of genetic variants with OS.ResultsTwo thirds of patients in both cohorts had metastases at CRPC diagnosis. Median OS from CRPC diagnosis was 3.6 (95%CI 3.3‐4.0) years in the test cohort and 4.6 (95%CI 3.8‐5.2) years in the validation cohort. Fifty‐nine SNPs in Hardy‐Weinberg equilibrium were analyzed. The major alleles of rs1318056 and rs1490311 in ABL2, and the minor alleles of rs2073917 and rs3764322 in ITGAL were associated with increased risk of death in the test cohort (adjusted‐HRs 1.27–1.39; adjusted‐p <0.05; false discovery rate <0.35). In the validation cohort, a similar association with OS was observed for rs1318056 in ABL2 (adjusted‐HR 1.44; 95%CI 0.89‐2.34) and rs2073917 in ITGAL (adjusted‐HR 1.41; 95%CI 0.82‐2.42). The associations did not reach statistical significance most likely due to the small sample size of the validation cohort (adjusted‐p = 0.142 and 0.209, respectively). Additional eQTL analysis indicated that minor alleles of rs1318056 and rs1490311 in ABL2 are associated with a lower ABL2 expression in blood.ConclusionsThese findings corroborate our initial work on the RNA expression of genes involved in immunity and inflammation from blood and clinical outcome and suggest that germline polymorphisms in ABL2 and ITGAL may be associated with the risk of death in men with CRPC. Further studies are needed to validate these findings and to explore their functional mechanisms.
Pro bono as a human capital learning and screening mechanism: Evidence from law firms
Authors: Burbano Vanessa C. , Mamer John , Snyder Jason 
Published: August 2018

Research Summary: Inquiry into CSR as a human capital management tool has suggested that firms benefit from such activities because employees value the meaningfulness of these activities, which influences motivation and retention. We propose an alternate avenue through which firms can benefit from an important type of socially responsible activity—pro bono services—that does not require that employees derive utility from the meaningfulness of the activity. We propose that pro bono activities can benefit firms through human capital learning and screening mechanisms, given the stretch roles that pro bono engagements allow. We formalize this argument in the legal services industry, where we provide primary evidence, a formal model, and empirical results using a panel dataset of the top 200 law firms to support this argument.Managerial Summary: We examine a type of CSR activity, pro bono engagements, in the context of the top 200 law firms in the United States. We show that firms can benefit from these engagements through human capital learning and screening mechanisms, due to the stretch roles that pro bono engagements allow junior lawyers. Our findings suggest that firms in which pro bono engagements provide stretch roles for junior employees can benefit from pro bono activities regardless of whether their employees value the meaningfulness or social impact of the pro bono work.
Hysteresis‐Free 1D Network Mixed Halide‐Perovskite Semitransparent Solar Cells
Authors: Ka Ibrahima , Asuo Ivy M. , Basu Suchismita , Fourmont Paul , Gedamu Dawit M. , Pignolet Alain , Cloutier Sylvain G. , Nechache Riad 
Published: August 2018

AbstractThe morphology of hybrid organic–inorganic perovskite films is known to strongly affect the performance of perovskite‐based solar cells. CH3NH3PbI3‐xClx (MAPbI3‐xClx) films have been previously fabricated with 100% surface coverage in glove boxes. In ambient air, fabrication generally relies on solvent engineering to obtain compact films. In contrast, this work explores the potential of altering the perovskites microstructure for solar cell engineering. This work starts with CH3NH3PbI3‐xClx, films with grain morphology carefully controlled by varying the deposition speed during the spin‐coating process to fabricate efficient and partially transparent solar cells. Devices produced with a CH3NH3PbI3‐xClx film and a compact thick top gold electrode reach a maximum efficiency of 10.2% but display a large photocurrent hysteresis. As it is demonstrated, the introduction of different concentrations of bromide in the precursor solution addresses the hysteresis issues and turns the film morphology into a partially transparent interconnected network of 1D microstructures. This approach leads to semitransparent solar cells with negligible hysteresis and efficiencies up to 7.2%, while allowing average transmission of 17% across the visible spectrum. This work demonstrates that the optimization of the perovskites composition can mitigate the hysteresis effects commonly attributed to the charge trapping within the perovskite film.