bluuebunny/crossref_metadata_2025_split huggingface dataset:
NMR Backbone Assignment of Large Proteins by Using 13Cα‐Only Triple‐Resonance Experiments
Authors: Wei Qingtao , Chen Jiajing , Mi Juan , Zhang Jiahai , Ruan Ke , Wu Jihui 
Published: June 2016

AbstractNuclear magnetic resonance (NMR) is a powerful tool to interrogate protein structure and dynamics residue by residue. However, the prerequisite chemical‐shift assignment remains a bottleneck for large proteins due to the fast relaxation and the frequency degeneracy of the 13Cα nuclei. Herein, we present a covariance NMR strategy to assign the backbone chemical shifts by using only HN(CO)CA and HNCA spectra that has a high sensitivity even for large proteins. By using the peak linear correlation coefficient (LCC), which is a sensitive probe even for tiny chemical‐shift displacements, we correctly identify the fidelity of approximately 92 % cross‐peaks in the covariance spectrum, which is thus a significant improvement on the approach developed by Snyder and Brüschweiler (66 %) and the use of spectral derivatives (50 %). Thus, we calculate the 4D covariance spectrum from HN(CO)CA and HNCA experiments, in which cross‐peaks with LCCs above a universal threshold are considered as true correlations. This 4D covariance spectrum enables the sequential assignment of a 42 kDa maltose binding protein (MBP), in which about 95 % residues are successfully assigned with a high accuracy of 98 %. Our LCC approach, therefore, paves the way for a residue‐by‐residue study of the backbone structure and dynamics of large proteins.
Pharmacokinetic Interaction Between Isavuconazole and a Fixed‐Dose Combination of Lopinavir 400 mg/Ritonavir 100 mg in Healthy Subjects
Authors: Yamazaki Takao , Desai Amit , Han David , Kato Kota , Kowalski Donna , Akhtar Shahzad , Lademacher Christopher , Kovanda Laura , Townsend Robert 
Published: June 2016

AbstractThis phase 1, open‐label study evaluated the pharmacokinetic effects of coadministration of the antifungal agent, isavuconazole (administered as its water‐soluble prodrug isavuconazonium sulfate), with the antiretroviral agent lopinavir/ritonavir in healthy adults. In part 1, 13 subjects were randomized to 2 arms to receive multiple doses of oral isavuconazole 100 mg either alone or with lopinavir/ritonavir 400/100 mg. In part 2, a different group of 55 subjects were randomized to 3 arms to receive multiple doses of oral isavuconazole 200 mg, either alone or with lopinavir/ritonavir 400/100 mg, or to receive oral lopinavir/ritonavir 400/100 mg alone. Mean area under the concentration‐time curve (AUC) following the last dose (AUCτ) and Cmax of isavuconazole increased by 113% and 96% in part 1 and by 96% and 74% in part 2 in the presence vs absence of lopinavir/ritonavir, respectively. Mean AUCτ and Cmax of lopinavir were 27% and 23% lower, and mean AUCτ and Cmax of ritonavir were 31% and 33% lower in the presence vs absence of isavuconazole, respectively. Mild to moderate gastrointestinal disorders were the most common adverse events experienced. These findings indicate that coadministration of lopinavir/ritonavir with isavuconazole can decrease the exposure of lopinavir/ritonavir and increase the exposure of isavuconazole. Patients should be monitored for reduced antiviral efficacy if these agents are coadministered.
A Case Of Neuroendocrine Carcinoma Expressing Myeloid Markers By Flow Cytometry And Review Of the Literature
Authors: Harrison Melody K. , Vanderjagt Timothy J. , Zhang Qian‐Yun 
Published: June 2016

BackgroundFlow cytometric data is often analyzed in isolation, without the benefit of clinical and morphologic context, and the findings must be interpreted with caution when unexpected results are obtained.MethodsA bone marrow aspirate from a 69‐year‐old female with incidentally discovered pancytopenia was initially analyzed by flow cytometry alone. The results were subsequently correlated with clinical, morphologic, immunohistochemical, and cytogenetic findings.ResultsMorphology and immunohistochemistry confirmed metastatic small cell carcinoma; by flow cytometric analysis, the neoplastic cells were positive for CD56 and showed unexpected expression of CD13 and CD117, raising the possibility of a myeloid neoplasm.ConclusionsFlow cytometric markers are not entirely sensitive or specific, and aberrant expression or lack of expression of certain markers can complicate interpretation, particularly when this is done in isolation (i.e., in reference laboratories). Whenever possible, clinical and morphologic correlation is strongly recommended. © 2016 International Clinical Cytometry Society
Digital fragment analysis of short tandem repeats by high‐throughput amplicon sequencing
Authors: Darby Brian J. , Erickson Shay F. , Hervey Samuel D. , Ellis‐Felege Susan N. 
Published: June 2016

AbstractHigh‐throughput sequencing has been proposed as a method to genotype microsatellites and overcome the four main technical drawbacks of capillary electrophoresis: amplification artifacts, imprecise sizing, length homoplasy, and limited multiplex capability. The objective of this project was to test a high‐throughput amplicon sequencing approach to fragment analysis of short tandem repeats and characterize its advantages and disadvantages against traditional capillary electrophoresis. We amplified and sequenced 12 muskrat microsatellite loci from 180 muskrat specimens and analyzed the sequencing data for precision of allele calling, propensity for amplification or sequencing artifacts, and for evidence of length homoplasy. Of the 294 total alleles, we detected by sequencing, only 164 alleles would have been detected by capillary electrophoresis as the remaining 130 alleles (44%) would have been hidden by length homoplasy. The ability to detect a greater number of unique alleles resulted in the ability to resolve greater population genetic structure. The primary advantages of fragment analysis by sequencing are the ability to precisely size fragments, resolve length homoplasy, multiplex many individuals and many loci into a single high‐throughput run, and compare data across projects and across laboratories (present and future) with minimal technical calibration. A significant disadvantage of fragment analysis by sequencing is that the method is only practical and cost‐effective when performed on batches of several hundred samples with multiple loci. Future work is needed to optimize throughput while minimizing costs and to update existing microsatellite allele calling and analysis programs to accommodate sequence‐aware microsatellite data.
Dentine oxygen isotopes (δ18O) as a proxy for odontocete distributions and movements
Authors: Matthews Cory J. D. , Longstaffe Fred J. , Ferguson Steven H. 
Published: June 2016

AbstractSpatial variation in marine oxygen isotope ratios (δ18O) resulting from differential evaporation rates and precipitation inputs is potentially useful for characterizing marine mammal distributions and tracking movements across δ18O gradients. Dentine hydroxyapatite contains carbonate and phosphate that precipitate in oxygen isotopic equilibrium with body water, which in odontocetes closely tracks the isotopic composition of ambient water. To test whether dentine oxygen isotope composition reliably records that of ambient water and can therefore serve as a proxy for odontocete distribution and movement patterns, we measured δ18O values of dentine structural carbonate (δ18OSC) and phosphate (δ18OP) of seven odontocete species (n = 55 individuals) from regional marine water bodies spanning a surface water δ18O range of several per mil. Mean dentine δ18OSC (range +21.2 to +25.5‰ VSMOW) and δ18OP (+16.7 to +20.3‰) values were strongly correlated with marine surface water δ18O values, with lower dentine δ18OSC and δ18OP values in high‐latitude regions (Arctic and Eastern North Pacific) and higher values in the Gulf of California, Gulf of Mexico, and Mediterranean Sea. Correlations between dentine δ18OSC and δ18OP values with marine surface water δ18O values indicate that sequential δ18O measurements along dentine, which grows incrementally and archives intra‐ and interannual isotopic composition over the lifetime of the animal, would be useful for characterizing residency within and movements among water bodies with strong δ18O gradients, particularly between polar and lower latitudes, or between oceans and marginal basins.
Effect of macropores on soil freezing and thawing with infiltration
Authors: Watanabe Kunio , Kugisaki Yuki 
Published: June 2016

AbstractAn understanding of heat transport and water flow in unsaturated soils experiencing freezing and thawing is important when considering hydrological and thermal processes in cold regions. Macropores, such as cracks, roots, and animal holes, provide efficient conduits for enhanced infiltration, resulting in a unique distribution of water content. However, the effects of macropores on soil freezing and thawing with infiltration have not been well studied. A one‐directional soil‐column freezing and thawing experiment was conducted using unsaturated sandy and silt loams with different sizes and numbers of macropores. During freezing, macropores were found to retard the formation of the frozen layer, depending on their size and number. During thawing, water flowed through macropores in the frozen layer and reached the underlying unfrozen soil. However, infiltrated water sometimes refroze in a macropore. The ice started to form at near inner wall of the macropore, grew to the centre, and blocked flow through the macropore. The blockage ice in the macropore could not melt until the frozen layer disappeared. Improving a soil freezing model to consider these macropore effects is required. Copyright © 2016 John Wiley & Sons, Ltd.
Indomethacin induces differential effects on in vitro endochondral ossification depending on the chondrocyte's differentiation stage
Authors: Caron Marjolein M. J. , Emans Pieter J. , Cremers Andy , Surtel Don A. M. , van Rhijn Lodewijk W. , Welting Tim J. M. 
Published: June 2016

ABSTRACTHeterotopic ossification (HO) is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. Heterotopic ossifications are described to develop via endochondral ossification and standard treatment is administration of indomethacin. It is currently unknown how indomethacin influences heterotopic ossification on a molecular level; therefore, we aimed to determine whether indomethacin might influence heterotopic ossification via impairing the chondrogenic phase of endochondral ossification. Progenitor cell models differentiating in the chondrogenic lineage (ATDC5, primary human bone marrow stem cells and ex vivo periosteal agarose cultures) were treated with increasing concentrations of indomethacin and a decrease in gene‐ and protein expression of chondrogenic and hypertrophic markers (measured by RT‐qPCR and immunoblotting) as well as decreased glycosamino‐glycan content (by alcian blue histochemistry) was observed. Even when hypertrophic differentiation was provoked, the addition of indomethacin resulted in decreased hypertrophic marker expression. Interestingly, when mature chondrocytes were treated with indomethacin, a clear increase in collagen type 2 expression was observed. Similarly, when ATDC5 cells and bone marrow stem cells were pre‐differentiated to obtain a chondrocyte phenotype and indomethacin was added from this time point onward, low concentrations of indomethacin also resulted in increased chondrogenic differentiation. Indomethacin induces differential effects on in vitro endochondral ossification, depending on the chondrocyte's differentiation stage, with complete inhibition of chondrogenic differentiation as the most pronounced action. This observation may provide a rational behind the elusive mode of action of indomethacin in the treatment of heterotopic ossifications. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:847–857, 2017.
Differentiation of Human Mesenchymal Stem Cells Toward Quality Cartilage Using Fibrinogen‐Based Nanofibers
Authors: Forget Jeremy , Awaja Firas , Gugutkov Dencho , Gustavsson Juhan , Gallego Ferrer Gloria , Coelho‐Sampaio Tatiana , Hochman‐Mendez Camila , Salmeron‐Sánchez Manuel , Altankov George 
Published: June 2016

Mimicking the complex intricacies of the extra cellular matrix including 3D configurations and aligned fibrous structures were traditionally perused for producing cartilage tissue from stem cells. This study shows that human adipose derived mesenchymal stem cells (hADMSCs) establishes significant chondrogenic differentiation and may generate quality cartilage when cultured on 2D and randomly oriented fibrinogen/poly‐lactic acid nanofibers compared to 3D sandwich‐like environments. The adhering cells show well‐developed focal adhesion complexes and actin cytoskeleton arrangements confirming the proper cellular interaction with either random or aligned nanofibers. However, quantitative reverse transcription‐polymerase chain reaction analysis for Collagen 2 and Collagen 10 genes expression confirms favorable chondrogenic response of hADMSCs on random nanofibers and shows substantially higher efficacy of their differentiation in 2D configuration versus 3D constructs. These findings introduce a new direction for cartilage tissue engineering through providing a simple platform for the routine generation of transplantable stem cells derived articular cartilage replacement that might improve joint function.
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Finely Tuned Thermo‐Responsive Block Copolymer Micelles for Photothermal Effect‐Triggered Efficient Cellular Internalization
Authors: Huang Mingming , Li Hui , Ke Wendong , Li Junjie , Zhao Chengai , Ge Zhishen 
Published: June 2016

Although biodegradable amphiphilic block copolymer micelles have been widely applied in the clinical applications as drug delivery nanocarriers, low‐efficiency cellular internalization frequently reduces therapeutic efficacy of the loaded drugs. Here, photothermal effect‐promoted cellular internalization of finely tuned thermo‐responsive amphiphilic biodegradable block copolymer nanocarriers via noninvasive stimuli of near‐infrared (NIR) light irradiation is demonstrated. Amphiphilic block copolymers, poly(ε‐caprolactone)‐block‐poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) (PCL‐b‐P(NIPAM‐co‐DMA)), are prepared with finely tuned compositions of P(NIPAM‐co‐DMA) for desirable lower critical solution temperature of the block copolymer micelles in aqueous solution. The block copolymers are then used to co‐encapsulate doxorubicin and indocyanine green, which show high encapsulation efficiency and significant photothermal effect upon exposure to NIR light irradiation. The photothermal effect‐induced collapse and hydrophilic‐to‐hydrophobic transition of P(NIPAM‐co‐DMA) shells significantly enhance the interactions between drug‐loaded micelles and cell membranes, which dramatically promote the cellular internalization of the micelles and therapeutic efficacy of loaded anticancer drugs.image
Reducible Dimeric Conjugates of Small Internally Segment Interfering RNA for Efficient Gene Silencing
Authors: Hong Cheol Am , Nam Yoon Sung 
Published: June 2016

The condensation of nucleic acids into compact nanoparticles with cationic carriers is a powerful tool for translocating exogenous nucleic acids into cells. To date, most efforts have been focused on the development of novel gene carriers for safe and efficient gene delivery. However, small interfering RNA (siRNA) is generally not strongly associated with cationic carriers due to its stiff structure and low spatial charge density. To overcome this limitation, this work introduces a well‐defined dimeric conjugate of small internally segment interfering RNA (sisiRNA) linked via a disulfide bond for enhanced cellular uptake and gene silencing. Dimeric sisiRNA is synthesized through oxidizing two monomeric sisiRNA molecules, each of which consists of a sense strand carrying a nick and an antisense strand modified with a thiol group at the 3′‐end. The nick in the sense strand enables the dimeric sisiRNA to be more effectively condensed into nanosized complexes due to the increased structural flexibility, which results in a higher gene silencing efficiency compared with the dimeric siRNA containing the intact sense strands. The results indicate that the discontinuity of the sense strands is a simple method of adding more flexibility to various siRNA‐based nanostructures for enhanced gene silencing.image
Hierarchical high‐order conforming C1 bases for quadrangular and triangular finite elements
Authors: Ferreira Luan J. F. , Bittencourt Marco L. 
Published: June 2016

SummaryWe present three new sets of C1 hierarchical high‐order tensor‐product bases for conforming finite elements. The first basis is a high‐order extension of the Bogner–Fox–Schmit basis. The edge and face functions are constructed using a combination of cubic Hermite and Jacobi polynomials with C1 global continuity on the common edges of elements. The second basis uses the tensor product of fifth‐order Hermite polynomials and high‐order functions and achieves global C1 continuity for meshes of quadrilaterals and C2 continuity on the element vertices. The third basis for triangles is also constructed using the tensor product of one‐dimensional functions defined in barycentric coordinates. It also has global C1 continuity on edges and C2 continuity on vertices. A patch test is applied to the three considered elements. Projection and plate problems with smooth fabricated solutions are solved, and the performance of the h‐ and p‐refinements are evaluated by comparing the approximation errors in the L2‐ and energy norms. A plate with singularity is then studied, and h‐ and p‐refinements are analysed. Finally, a transient problem with implicit time integration is considered. The results show exponential convergence rates with increasing polynomial order for the triangular and quadrilateral meshes of non‐distorted and distorted elements. Copyright © 2016 John Wiley & Sons, Ltd.
Proper generalized decomposition solution of the parameterized Helmholtz problem: application to inverse geophysical problems
Authors: Signorini Marianna , Zlotnik Sergio , Díez Pedro 
Published: June 2016

SummaryThe identification of the geological structure from seismic data is formulated as an inverse problem. The properties and the shape of the rock formations in the subsoil are described by material and geometric parameters, which are taken as input data for a predictive model. Here, the model is based on the Helmholtz equation, describing the acoustic response of the system for a given wave length. Thus, the inverse problem consists in identifying the values of these parameters such that the output of the model agrees the best with observations. This optimization algorithm requires multiple queries to the model with different values of the parameters. Reduced order models are especially well suited to significantly reduce the computational overhead of the multiple evaluations of the model.In particular, the proper generalized decomposition produces a solution explicitly stating the parametric dependence, where the parameters play the same role as the physical coordinates. A proper generalized decomposition solver is devised to inexpensively explore the parametric space along the iterative process. This exploration of the parametric space is in fact seen as a post‐process of the generalized solution. The approach adopted demonstrates its viability when tested in two illustrative examples. Copyright © 2016 John Wiley & Sons, Ltd.
Bone marrow transplantation for CVID‐like humoral immune deficiency associated with red cell aplasia
Authors: Sayour Elias J. , Mousallem Talal , Van Mater David , Wang Endi , Martin Paul , Buckley Rebecca H. , Barfield Raymond C. 
Published: June 2016

AbstractPatients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID‐like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids.
Biopsychosocial problem‐related distress in cancer: examining the role of sex and age
Authors: Clark Karen , Bergerot Cristiane Decat , Philip Errol J. , Buga Sorin , Obenchain Richard , Loscalzo Matthew J. 
Published: June 2016

AbstractBackgroundThe current study explores how sex and age relate to biopsychosocial distress by applying a large‐scale analysis among individuals diagnosed with a variety of cancers.MethodsA retrospective study was conducted involving 6462 patients treated for cancer at a National Cancer Institute‐designated comprehensive cancer center between 2009 and 2014. Patients were asked to complete the biopsychosocial problem‐related distress touchscreen instrument prior to starting treatment as part of their routine clinical care.ResultsThere was a significant interaction of age and sex on the total number of problems rated as high distress and the total number of problems that prompted a request to talk with a member of the team. Male patients between 18 and 39 reported significantly more problems as high distress than female patients in the same age group (mean = 5.34 and mean = 4.92, respectively; p = 0.005). A similar trend was found where male patients between 18–39 and 40–64 requested to talk with a member of the team significantly more often than female patients in these same age groups (mean = 3.25 and mean = 3.22 vs. mean = 2.70 and mean = 3.07, respectively; p = 0.016).ConclusionsThe results of the current study serve to refute generalizations regarding age or gender demographics and support preferences and thus reinforce the need to offer services in the context of cancer in flexible and varied ways. Copyright © 2016 John Wiley & Sons, Ltd.