bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of response and progression in patients with BRAF‐mutant melanoma metastatic to the brain who were treated with dabrafenib
Authors: Azer Mary W. F . , Menzies Alexander M. , Haydu Lauren E. , Kefford Richard F. , Long Georgina V. 
Published: November 2013

BACKGROUNDDabrafenib has activity in patients with brain metastases, but little is known of the relative efficacy of treatment within and outside the brain. This study sought to examine the intracranial (IC) and extracranial (EC) patterns of response and progression in patients with active melanoma brain metastases treated with dabrafenib.METHODSClinicopathologic parameters were collected on patients with active brain metastases enrolled in the phase 1 and 2 studies of dabrafenib at a single institution. RECIST (Response Evaluation Criteria In Solid Tumors) response and progression‐free survival (PFS) were prospectively assessed by disease site (IC versus EC). Treatments received after disease progression were also assessed.RESULTSA total of 23 patients were studied. Response rates were similar in IC (78%) and EC (90%) sites (P = .416). IC and EC response was concordant in 71% of patients. Median site‐specific PFS was identical in both IC and EC sites (23.6 weeks, P = .465), and exceeded whole‐body PFS determined by RECIST (16.3 weeks). Of 20 patients with progressive disease (PD), 6 had IC PD only, 6 had EC PD only, and 8 had PD in both sites. In those with isolated intracranial PD, 5 of 6 underwent local therapy to the brain and continued on dabrafenib longer than 30 days.CONCLUSIONSIC and EC melanoma metastases respond similarly to dabrafenib. There is no dominant site or pattern of disease progression in patients with brain metastases treated with dabrafenib. Salvage local therapy is possible in most patients after IC disease progression, with ongoing dabrafenib treatment possible in a subset of patients. Cancer 2014;120:530–536. © 2013 American Cancer Society.
Localization Microscopy using Noncovalent Fluorogen Activation by Genetically Encoded Fluorogen‐Activating Proteins.
Authors: Yan Qi , Schwartz Samantha L. , Maji Suvrajit , Huang Fang , Szent‐Gyorgyi Chris , Lidke Diane S. , Lidke Keith A. , Bruchez Marcel P. 
Published: November 2013

AbstractThe noncovalent equilibrium activation of a fluorogenic malachite green dye and its cognate fluorogen‐activating protein (FAP) can produce a sparse labeling distribution of densely tagged genetically encoded proteins, enabling single molecule detection and super‐resolution imaging in fixed and living cells. These sparse labeling conditions are achieved by control of the dye concentration in the milieu, and do not require any photoswitching or photoactivation. The labeling is achieved by using physiological buffers and cellular media, in which additives and switching buffers are not required to obtain super‐resolution images. We evaluate the super‐resolution properties and images obtained from a selected FAP clone fused to actin, and show that the photon counts per object are between those typically reported for fluorescent proteins and switching‐dye pairs, resulting in 10–30 nm localization precision per object. This labeling strategy complements existing approaches, and may simplify multicolor labeling of cellular structures.
Synergistic effects of the invasive Chinese tallow (Triadica sebifera) and climate change on aquatic amphibian survival
Authors: Saenz Daniel , Fucik Erin M. , Kwiatkowski Matthew A. 
Published: November 2013

AbstractChanges in climate and the introduction of invasive species are two major stressors to amphibians, although little is known about the interaction between these two factors with regard to impacts on amphibians. We focused our study on an invasive tree species, the Chinese tallow (Triadica sebifera), that annually sheds its leaves and produces leaf litter that is known to negatively impact aquatic amphibian survival. The purpose of our research was to determine whether the timing of leaf fall from Chinese tallow and the timing of amphibian breeding (determined by weather) influence survival of amphibian larvae. We simulated a range of winter weather scenarios, ranging from cold to warm, by altering the relative timing of when leaf litter and amphibian larvae were introduced into aquatic mesocosms. Our results indicate that amphibian larvae survival was greatly affected by the length of time Chinese tallow leaf litter decomposes in water prior to the introduction of the larvae. Larvae in treatments simulating warm winters (early amphibian breeding) were introduced to the mesocosms early in the aquatic decomposition process of the leaf litter and had significantly lower survival compared with cold winters (late amphibian breeding), likely due to significantly lower dissolved oxygen levels. Shifts to earlier breeding phenology, linked to warming climate, have already been observed in many amphibian taxa, and with most climate models predicting a significant warming trend over the next century, the trend toward earlier breeding should continue if not increase. Our results strongly suggest that a warming climate can interact with the effects of invasive plant species, in ways we have not previously considered, to reduce the survival of an already declining group of organisms.
The Effects of Electron‐Donating Substituents on [Ir(bpy)Cp*Cl]+: Water Oxidation versus Ligand Oxidative Modifications
Authors: Zhang Teng , deKrafft Kathryn E. , Wang Jin‐Liang , Wang Cheng , Lin Wenbin 
Published: November 2013

AbstractA series of [Ir(bpy)Cp*Cl]Cl (bpy: 2,2′‐bipyridine; Cp*: pentamethylcyclopentadienyl) complexes with 4,4′‐ and 6,6′‐substituents on the bipyridine ring were synthesized and used for water oxidation both electrochemically and with chemical oxidants. Under electrochemical water‐oxidation reaction (WOR) conditions at pH = 1, blue films were observed to deposit on the electrode surfaces for all of the complexes, without the detection of oxygen. For chemically driven WORs, three oxidants with different overpotentials and electron‐transfer kinetics led to very different behaviors. [Ru(bpy)3]3+ was shown to slowly oxidize the ligands without generating oxygen at pH = 3.7. With NaIO4 as the oxidant at neutral pH, oxygen generation was observed, but ligand oxidation was also seen for the complexes with electron‐donating substituents such as –OMe or –OH groups. With Ce4+ as the oxidant at pH = 1, a competition between water oxidation and ligand decomposition existed; less ligand decomposition was observed for catalysts that are more active for WOR. These results indicate the intricate nature of molecule water‐oxidation catalysts and their complex behaviors that are highly sensitive to water‐oxidation conditions.
Intrinsic Reason for the Morphology Dependence of Luminescent Behavior: A Case Study with GdVO4:Eu3+ Nanocrystals
Authors: Yang Liusai , Li Guangshe , Zhao Minglei , Zheng Jing , Luo Dong , Zheng Yunlong , Li Liping 
Published: November 2013

AbstractRare‐earth orthovanadates, a kind of prototypical host, have received extensive attentions owing to their important applications. Although there has been great progress in the control of morphologies and optimzation of properties, the intrinsic reasons for the morphology dependence of their luminescence are still unclear. In this work, we chose GdVO4:Eu3+ as a model compound to study. By varying the surfactant dose involved under mild hydrothermal conditions, several distinct morphologies, such as nanorods, nanowafers, nanoparticles, and snowballs were prepared. Depending on the morphologies and residual surfactant content, surface cationic nonstoichiometry and defects, especially for unstable VO4 groups, were demonstrated to exist in GdVO4:Eu3+ nanocrystals. The first experimental evidence for the relationship between surface defect states and luminescent emission of GdVO4:Eu3+ nanocrystals is presented.
Synthesis and Structures of Mixed‐Valence Oxido‐Bridged Diruthenium Complexes Bearing Ethylbis(2‐pyridylmethyl)amine
Authors: Suzuki Tomoyo , Matsuya Kazuhiro , Kawamoto Tatsuya , Nagao Hirotaka 
Published: November 2013

AbstractTrihalogenoruthenium(III) complexes bearing an ethylbis(2‐pyridylmethyl)amine (ebpma) ligand, fac‐[RuIIIX3(ebpma)] (X = Cl, Br), were reduced by zinc in acetone that contained halogeno acid to afford a reddish‐orange solution. Two kinds of dinuclear complexes were synthesized from the solution. After removing the remaining zinc and adding counterions such as PF6– and BF4– with water, the solution was allowed to stand under air until the color of the solution changed. New oxido‐bridged dinuclear complexes of mixed‐valence RuIII–RuIV [{RuIII,IVX2(ebpma)}2(μ‐O)]Y (X = Cl, Y = PF6, [1]PF6; Y = BF4, [1]BF4; X = Br, Y = PF6, [2]PF6; Y = BF4, [2]BF4), which showed a similar framework to the reported water oxidation catalysts, were obtained as deep‐colored solids. In the reaction without addition of extra water, a different mixed‐valence dinuclear complex of RuII–RuIII [{RuII,III(ebpma)}2(μ‐Cl)3]2+, for which the metal centers were triply bridged by three chlorides, was formed. The synthetic procedures are useful for the development of multinuclear frameworks that function as molecular catalysts for redox reactions such as water oxidation.
A General Framework for Association Tests With Multivariate Traits in Large‐Scale Genomics Studies
Authors: He Qianchuan , Avery Christy L. , Lin Dan‐Yu 
Published: November 2013

ABSTRACTGenetic association studies often collect data on multiple traits that are correlated. Discovery of genetic variants influencing multiple traits can lead to better understanding of the etiology of complex human diseases. Conventional univariate association tests may miss variants that have weak or moderate effects on individual traits. We propose several multivariate test statistics to complement univariate tests. Our framework covers both studies of unrelated individuals and family studies and allows any type/mixture of traits. We relate the marginal distributions of multivariate traits to genetic variants and covariates through generalized linear models without modeling the dependence among the traits or family members. We construct score‐type statistics, which are computationally fast and numerically stable even in the presence of covariates and which can be combined efficiently across studies with different designs and arbitrary patterns of missing data. We compare the power of the test statistics both theoretically and empirically. We provide a strategy to determine genome‐wide significance that properly accounts for the linkage disequilibrium (LD) of genetic variants. The application of the new methods to the meta‐analysis of five major cardiovascular cohort studies identifies a new locus (HSCB) that is pleiotropic for the four traits analyzed.
Statistical Testing of Shared Genetic Control for Potentially Related Traits
Authors: Wallace Chris 
Published: November 2013

ABSTRACTIntegration of data from genome‐wide single nucleotide polymorphism (SNP) association studies of different traits should allow researchers to disentangle the genetics of potentially related traits within individually associated regions. Formal statistical colocalisation testing of individual regions requires selection of a set of SNPs summarising the association in a region. We show that the SNP selection method greatly affects type 1 error rates, with published studies having used methods expected to result in substantially inflated type 1 error rates. We show that either avoiding variable selection and instead testing the most informative principal components or integrating over variable selection using Bayesian model averaging can help control type 1 error rates. Application to data from Graves' disease and Hashimoto's thyroiditis reveals a common genetic signature across seven regions shared between the diseases, and indicates that in five of six regions associated with Graves' disease and not Hashimoto's thyroiditis, this more likely reflects genuine absence of association with the latter rather than lack of power. Our examination, by simulation, of the performance of colocalisation tests and associated software will foster more widespread adoption of formal colocalisation testing. Given the increasing availability of large expression and genetic association datasets from disease‐relevant tissue and purified cell populations, coupled with identification of regulatory sequences by projects such as ENCODE, colocalisation analysis has the potential to reveal both shared genetic signatures of related traits and causal disease genes and tissues.
TGFβ Inducible Early Gene-1 Plays an Important Role in Mediating Estrogen Signaling in the Skeleton
Authors: Hawse John R , Pitel Kevin S , Cicek Muzaffer , Philbrick Kenneth A , Gingery Anne , Peters Kenneth D , Syed Farhan A , Ingle James N , Suman Vera J , Iwaniec Urszula T , Turner Russell T , Spelsberg Thomas C , Subramaniam Malayannan 
Published: November 2013

ABSTRACT

TGFβ Inducible Early Gene-1 (TIEG1) knockout (KO) mice display a sex-specific osteopenic phenotype characterized by low bone mineral density, bone mineral content, and overall loss of bone strength in female mice. We, therefore, speculated that loss of TIEG1 expression would impair the actions of estrogen on bone in female mice. To test this hypothesis, we employed an ovariectomy (OVX) and estrogen replacement model system to comprehensively analyze the role of TIEG1 in mediating estrogen signaling in bone at the tissue, cell, and biochemical level. Dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-CT analyses revealed that loss of TIEG1 expression diminished the effects of estrogen throughout the skeleton and within multiple bone compartments. Estrogen exposure also led to reductions in bone formation rates and mineralizing perimeter in wild-type mice with little to no effects on these parameters in TIEG1 KO mice. Osteoclast perimeter per bone perimeter and resorptive activity as determined by serum levels of CTX-1 were differentially regulated after estrogen treatment in TIEG1 KO mice compared with wild-type littermates. No significant differences were detected in serum levels of P1NP between wild-type and TIEG1 KO mice. Taken together, these data implicate an important role for TIEG1 in mediating estrogen signaling throughout the mouse skeleton and suggest that defects in this pathway are likely to contribute to the sex-specific osteopenic phenotype observed in female TIEG1 KO mice. © 2014 American Society for Bone and Mineral Research.
Commitment to nutritional endoderm in Eleutherodactylus coqui involves altered nodal signaling and global transcriptional repression
Authors: Chatterjee Suman , Elinson Richard P. 
Published: November 2013

ABSTRACTThe vegetal cells of a Xenopus laevis embryo commit to mesendoderm via the Nodal‐signaling pathway. In the direct developing frog Eleutherodactylus coqui, mesendoderm is specified at the marginal zone of the early gastrula, and vegetal core cells transform into nutritional endoderm. Nutritional endoderm, a novel tissue, consists of transient, yolky cells that provide nutrition but remain undifferentiated. We report a dual regulation for the generation of nutritional endoderm. First, differential expressions of the Nodal‐signal transducers Smad2 and Smad4 were observed during early gastrulation between the marginal zone and the vegetal core cells. Although EcSmad2 RNA as well as total and activated Smad2 protein were detected in the vegetal core, Smad4 protein was expressed less in vegetal core during early gastrulation. Only 12% and 50% of vegetal core cells were positive for nuclear Smad2 and Smad4 signals respectively compared to 100% of marginal zone cells. These results suggest a signaling disruption in the vegetal core. Second, vegetal core cells were transcriptionally repressed. At the blastula stage, both marginal zone and vegetal core cells were transcriptionally silent, but during early gastrulation, only marginal zone cells became transcriptionally active. This indicates the occurrence of a mid‐blastula transition in the marginal zone by early gastrulation, but global transcriptional repression persisted in the vegetal core and its derivative, nutritional endoderm, throughout development. We have described a novel mechanism, which prevents differentiation of the vegetal core through differential Nodal‐signaling and global transcriptional repression. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 27–44, 2014. © 2013 Wiley Periodicals, Inc.
Looking for biological factors to predict the risk of active cytomegalovirus infection in non‐immunosuppressed critically ill patients
Authors: Bravo Dayana , Clari María A. , Aguilar Gerardo , Belda Javier , Giménez Estela , Carbonell José A. , Henao Liliana , Navarro David 
Published: November 2013

ABSTRACTThe identification of non‐immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin‐10 IL‐10), and monocyte chemoattractant protein‐1 (MCP‐1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV‐specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46%) developed an episode of active CMV infection. The incidence rate of active CMV infection was not significantly associated with any single nucleotide polymorphisms. A trend towards a lower incidence of active CMV infection (P = 0.06) was noted in patients harboring the IL10 C/C genotype. Patients carrying the CCR5 A/A genotype had high CMV DNA loads in tracheal aspirates. The serum levels of CMV IgGs did not differ significantly between patients with a subsequent episode of active CMV infection (median, 217 IU/mL) or without one (median, 494 IU/mL). Detection of CMV DNA in saliva did not usually precede that in plasma and/or tracheal aspirates. In summary, the analysis of single nucleotide polymorphisms in the IL10 and CCR5 genes might help to determine the risk of active CMV infection or the level of CMV replication within episodes, respectively, in non‐immunosuppressed critically ill patients. J. Med. Virol. 86:827–833, 2014. © 2013 Wiley Periodicals, Inc.
Full‐length genome characterization and genetic relatedness analysis of hepatitis A virus outbreak strains associated with acute liver failure among children
Authors: Vaughan Gilberto , Forbi Joseph C. , Xia Guo‐Liang , Fonseca‐Ford Maureen , Vazquez Roberto , Khudyakov Yury E. , Montiel Sonia , Waterman Steve , Alpuche Celia , Gonçalves Rossi Livia Maria , Luna Norma 
Published: November 2013

AbstractClinical infection by hepatitis A virus (HAV) is generally self‐limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full‐genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common‐source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes. J. Med. Virol. 86:202–208, 2014. © 2013 Wiley Periodicals, Inc.
Tropical Ulcer on a Human Tibia from 5000 Years Ago in Northern Italy
Authors: Micheletti Cremasco M. , Merlo F. , Fulcheri E. , Rothschild B. M. 
Published: November 2013

AbstractThe term tropical ulcer, as applied to bone pathology, describes the specific pathologic phenomenon of the presence of a well‐defined osteomatous shelf formation on the anteromedial aspect of the tibia. Despite the appellation ‘tropical,’ this pathology is not geographically limited to tropical regions, although it has not previously been reported from continental Europe. Observations of a 4583 BP burial from the Tanaro River area of Northern Italy represent the first such case. Dating of the site to the time of climate change at the end of the first Glacial suggests that hot–warm, humid conditions may have allowed the occurrence of this bone pathology, the first observed in continental Europe. A second explanation is the possible migration of an individual to Italy from an area that is more conventionally considered tropical. Copyright © 2013 John Wiley & Sons, Ltd.
Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging
Authors: Kiss András , Smith Donald F. , Jungmann Julia H. , Heeren Ron M. A. 
Published: November 2013

RATIONALEMicroscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high‐speed imaging of biomolecules from complex surfaces. Technological developments such as new position‐sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra‐high spatial resolution, sample throughput and sensitivity.METHODSIn this work, a C60 primary source was combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high‐voltage post‐acceleration capabilities. The system's mass spectral and imaging performance is tested with various benchmark samples and thin tissue sections.RESULTSThe high secondary ion yield (with respect to 'traditional' monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal‐to‐noise ratio are improved compared with other microscope mode imaging systems, all at high spatial resolution.CONCLUSIONSWe have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging. Copyright © 2013 John Wiley & Sons, Ltd.