bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Puzzling Disagreement between Observations and Numerical Models in the Central Gulf of Mexico
Authors: Sturges Wilton , Bozec Alexandra 
Published: September 2013

Abstract
Two large, independent sets of direct observations in the central Gulf of Mexico show a mean near-surface flow of ~10 cm s−1 to the west, concentrated in the northern and southern Gulf. Numerical models that the authors have examined do not produce this mean westward flow. The observed speeds appear to be almost an order of magnitude larger than the estimated errors; this paper studies the observations to estimate carefully the possible errors involved and compares the observations with model results. The flow to the west in the southern Gulf is presumably wind driven on the shallow parts of the shelf, and, in slightly deeper water at the outer edges of the shelf, is possibly the result of southward Sverdrup interior flow driven by the negative curl of the wind stress. In another possibly related issue, long-term deep current-meter observations in the northern Gulf at ~1000 m and below find flow to the west, whereas some models find flow to the east. The flow proposed here assumes a mean flow to the west above roughly 300 m, with a required return flow in deep water. The difference between the deep observations and the models will produce a slope of pressure surfaces of the opposite sign below 1000 m, reversing the direction of upper-layer geostrophic flow in the models.
Human C-reactive protein induces endothelial dysfunction in biobreeding diabetic rats
Authors: Jialal Ishwarlal , Kaur Harmeet , Devaraj Sridevi , Smith Gerred 
Published: September 2013

Objective: C-reactive protein (CRP) levels in diabetes predict cardiovascular events. Also, human CRP (hCRP) exacerbated the proinflammatory, pro-oxidant and procoagulant states in a spontaneous model of type 1 diabetes mellitus (T1DM), the biobreeding (BB) rat. Since there is a paucity of data examining the role of CRP on endothelial dysfunction in animal models of diabetes, we tested this hypothesis in the diabetic BB rat. Methods: Diabetic BB rats ( n = 4 per group) were injected with human serum albumin (HSA) or hCRP [hCRP = 20 mg/kg body weight; intraperitoneal (IP)] for three consecutive days. The rats were euthanized on day 4. Biomarkers that were assayed included endothelin-1 (ET-1), soluble intracellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (vWF) and 6-keto prostaglandin F1-alpha (6-keto PGF1-α) in plasma. Results: hCRP administration resulted in a significant increase in plasma levels. Furthermore, hCRP-treated rats had significantly increased circulating levels of ET-1 (1.12 ± 0.6 pg/mL versus 0.4 ± 0.21 pg/mL), vWF (45 ± 2.4 ng/mL versus 34 ± 7 ng/mL) and sICAM-1 (41 ± 3 ng/mL versus 34 ± 3.4 ng/mL) compared to HSA-treated rats ( p < 0.05). There was no significant effect on 6-keto PGF1-α levels. Conclusion: Hence, in this preliminary report, we make the novel observation that hCRP induces endothelial dysfunction in a spontaneous model of T1DM, and this could have implications for the vascular complications in diabetics.
Blastocystis, an unrecognized parasite: an overview of pathogenesis and diagnosis
Authors: Wawrzyniak Ivan , Poirier Philippe , Viscogliosi Eric , Dionigia Meloni , Texier Catherine , Delbac Frédéric , Alaoui Hicham El 
Published: September 2013

Blastocystis sp. is among the few enteric parasites with a prevalence that often exceeds 5% in the general population of industrialized countries and can reach 30–60% in developing countries. This parasite is frequently found in people who are immunocompromised (patients with human immunodeficiency virus/acquired immunodeficiency syndrome or cancer) and a higher risk of Blastocystis sp. infection has been found in people with close animal contact. Such prevalence in the human population and the zoonotic potential naturally raise questions about the impact of these parasites on public health and has increased interest in this area. Recent in vitro and in vivo studies have shed new light on the pathogenic power of this parasite, suggesting that Blastocystis sp. infection is associated with a variety of gastrointestinal disorders, may play a significant role in irritable bowel syndrome, and may be linked with cutaneous lesions (urticaria). Despite recent significant advances in the knowledge of the extensive genetic diversity of this species, the identification of extracellular proteases as virulence factors and the publication of one isolate genome, many aspects of the biology of Blastocystis sp. remain poorly investigated. In this review, we investigate several biological aspects of Blastocystis sp. (diversity and epidemiology, diagnosis tools and pathophysiology). These data pave the way for the following challenges concerning Blastocystis sp. research: deciphering key biological mechanisms and pathways of this parasite and clarification of its clinical impact in humans.
DNA methylation of Runx1 regulatory regions correlates with transition from primitive to definitive hematopoietic potential in vitro and in vivo
Authors: Webber Beau R. , Iacovino Michelina , Choi Si Ho , Tolar Jakub , Kyba Michael , Blazar Bruce R. 
Published: September 2013

Key PointsDNA methylation profile of Runx1 locus correlates with transcriptional activity and promoter usage during blood development. Distal promoter hypomethylation is a novel signature of definitive hematopoiesis and is promoted in vitro by direct interaction with HoxB4.
Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study
Authors: Cruz Conrad Russell Y. , Micklethwaite Kenneth P. , Savoldo Barbara , Ramos Carlos A. , Lam Sharon , Ku Stephanie , Diouf Oumar , Liu Enli , Barrett A. John , Ito Sawa , Shpall Elizabeth J. , Krance Robert A. , Kamble Rammurti T. , Carrum George , Hosing Chitra M. , Gee Adrian P. , Mei Zhuyong , Grilley Bambi J. , Heslop Helen E. , Rooney Cliona M. , Brenner Malcolm K. , Bollard Catherine M. , Dotti Gianpietro 
Published: September 2013

Key Points
Allogeneic CD19-CAR VSTs are well tolerated by patients with relapsed B-cell malignancies post-HSCT. At periods of CD19-CAR VST persistence, these cells demonstrate antitumor activity.
Myosin VI contributes to maintaining epithelial barrier function
Authors: Liao Yu-Wei , Wu Xing-Mao , Jia Jia , Wu Xiao-Lei , Hong Tao , Meng Ling-Xin , Wu Xiu-Ying 
Published: September 2013

Abstract

Background
Epithelial barrier dysfunction is associated with the pathogenesis of a number of immune inflammations; the etiology is not fully understood. The fusion of endosome/lysosome is a critical process in the degradation of endocytic antigens in epithelial cells. Recent reports indicate that myosin VI (myo6) is involved in the activities of endosomes. The present study aims to investigate the role of myo6 in epithelial barrier dysfunction.

Results
The endosome accumulation was observed in myo6-deficient Rmcs. More than 80% endosomes were fused with lysosomes in naïve Rmcs while less than 30% endosomes were fused with lysosomes in the myo6-deficient Rmcs. The myo6-deficient Rmc monolayers showed high permeability to a macromolecular antigen, ovalbumin, the latter still conserved the antigenicity, which induced strong T cell activation.

Conclusions
We conclude that myo6 plays a critical role in the fusion of endosome/lysosome in Rmc epithelial cells. Deficiency of myo6 compromises the epithelial barrier function.
An EM algorithm based on an internal list for estimating haplotype distributions of rare variants from pooled genotype data
Authors: Kuk Anthony YC , Li Xiang , Xu Jinfeng 
Published: September 2013

Abstract

Background
Pooling is a cost effective way to collect data for genetic association studies, particularly for rare genetic variants. It is of interest to estimate the haplotype frequencies, which contain more information than single locus statistics. By viewing the pooled genotype data as incomplete data, the expectation-maximization (EM) algorithm is the natural algorithm to use, but it is computationally intensive. A recent proposal to reduce the computational burden is to make use of database information to form a list of frequently occurring haplotypes, and to restrict the haplotypes to come from this list only in implementing the EM algorithm. There is, however, the danger of using an incorrect list, and there may not be enough database information to form a list externally in some applications.

Results
We investigate the possibility of creating an internal list from the data at hand. One way to form such a list is to collapse the observed total minor allele frequencies to “zero” or “at least one”, which is shown to have the desirable effect of amplifying the haplotype frequencies. To improve coverage, we propose ways to add and remove haplotypes from the list, and a benchmarking method to determine the frequency threshold for removing haplotypes. Simulation results show that the EM estimates based on a suitably augmented and trimmed collapsed data list (ATCDL) perform satisfactorily. In two scenarios involving 25 and 32 loci respectively, the EM-ATCDL estimates outperform the EM estimates based on other lists as well as the collapsed data maximum likelihood estimates.

Conclusions
The proposed augmented and trimmed CD list is a useful list for the EM algorithm to base upon in estimating the haplotype distributions of rare variants. It can handle more markers and larger pool size than existing methods, and the resulting EM-ATCDL estimates are more efficient than the EM estimates based on other lists.
Genome and transcriptome sequencing of the halophilic fungus Wallemia ichthyophaga: haloadaptations present and absent
Authors: Zajc Janja , Liu Yongfeng , Dai Wenkui , Yang Zhenyu , Hu Jingzhi , Gostinčar Cene , Gunde-Cimerman Nina 
Published: September 2013

Abstract

Background
The basidomycete Wallemia ichthyophaga from the phylogenetically distinct class Wallemiomycetes is the most halophilic fungus known to date. It requires at least 10% NaCl and thrives in saturated salt solution. To investigate the genomic basis of this exceptional phenotype, we obtained a de-novo genome sequence of the species type-strain and analysed its transcriptomic response to conditions close to the limits of its lower and upper salinity range.

Results
The unusually compact genome is 9.6 Mb large and contains 1.67% repetitive sequences. Only 4884 predicted protein coding genes cover almost three quarters of the sequence. Of 639 differentially expressed genes, two thirds are more expressed at lower salinity. Phylogenomic analysis based on the largest dataset used to date (whole proteomes) positions Wallemiomycetes as a 250-million-year-old sister group of Agaricomycotina. Contrary to the closely related species Wallemia sebi, W. ichthyophaga appears to have lost the ability for sexual reproduction. Several protein families are significantly expanded or contracted in the genome. Among these, there are the P-type ATPase cation transporters, but not the sodium/ hydrogen exchanger family. Transcription of all but three cation transporters is not salt dependent. The analysis also reveals a significant enrichment in hydrophobins, which are cell-wall proteins with multiple cellular functions. Half of these are differentially expressed, and most contain an unusually large number of acidic amino acids. This discovery is of particular interest due to the numerous applications of hydrophobines from other fungi in industry, pharmaceutics and medicine.

Conclusions

W. ichthyophaga is an extremophilic specialist that shows only low levels of adaptability and genetic recombination. This is reflected in the characteristics of its genome and its transcriptomic response to salt. No unusual traits were observed in common salt-tolerance mechanisms, such as transport of inorganic ions or synthesis of compatible solutes. Instead, various data indicate a role of the cell wall of W. ichthyophaga in its response to salt. Availability of the genomic sequence is expected to facilitate further research into this unique species, and shed more light on adaptations that allow it to thrive in conditions lethal to most other eukaryotes.
Derivation and assessment of risk prediction models using case-cohort data
Authors: Sanderson Jean , Thompson Simon G , White Ian R , Aspelund Thor , Pennells Lisa 
Published: September 2013

AbstractBackgroundCase-cohort studies are increasingly used to quantify the association of novel factors with disease risk. Conventional measures of predictive ability need modification for this design. We show how Harrell’s C-index, Royston’s D, and the category-based and continuous versions of the net reclassification index (NRI) can be adapted.MethodsWe simulated full cohort and case-cohort data, with sampling fractions ranging from 1% to 90%, using covariates from a cohort study of coronary heart disease, and two incidence rates. We then compared the accuracy and precision of the proposed risk prediction metrics.ResultsThe C-index and D must be weighted in order to obtain unbiased results. The NRI does not need modification, provided that the relevant non-subcohort cases are excluded from the calculation. The empirical standard errors across simulations were consistent with analytical standard errors for the C-index and D but not for the NRI. Good relative efficiency of the prediction metrics was observed in our examples, provided the sampling fraction was above 40% for the C-index, 60% for D, or 30% for the NRI. Stata code is made available.ConclusionsCase-cohort designs can be used to provide unbiased estimates of the C-index, D measure and NRI.
Mycobacterium tuberculosisis the causative agent of tuberculosis in the southern ecological zones of Cameroon, as shown by genetic analysis
Authors: Assam Jean Paul Assam , Beng Véronique Penlap , Cho-Ngwa Fidelis , Toukam Michel , Ngoh Ane-Anyangwe Irene , Kitavi Mercy , Nzuki Inoster , Nyonka Juliette N , Tata Emilienne , Tedom Jean Claude , Skilton Robert A , Pelle Roger , Titanji Vincent P K 
Published: September 2013

Abstract

Background
Tuberculosis (TB) is a major cause of mortality and suffering worldwide, with over 95% of TB deaths occurring in low- and middle-income countries. In recent years, molecular typing methods have been widely used in epidemiological studies to aid the control of TB, but this usage has not been the case with many African countries, including Cameroon. The aims of the present investigation were to identify and evaluate the diversity of the Mycobacterium tuberculosis complex (MTBC) isolates circulating in two ecological zones of Cameroon, seven years after the last studies in the West Region, and after the re-organization of the National TB Control Program (NTBCP). These were expected to shed light also on the transmission of TB in the country. The study was conducted from February to July 2009. During this period, 169 patients with symptomatic disease and with sputum cultures that were positive for MTBC were randomly selected for the study from amongst 964 suspected patients in the savannah mosaic zone (West and North West regions) and the tropical rainforest zone (Central region). After culture and diagnosis, DNA was extracted from each of the MTBC isolates and transported to the BecA-ILRI Hub in Nairobi, Kenya for molecular analysis.

Methods
Genetic characterization was done by mycobacterial interspersed repetitive unit–variable number tandem repeat typing (MIRU-VNTR) and Spoligotyping.

Results
Molecular analysis showed that all TB cases reported in this study were caused by infections with Mycobacterium tuberculosis (98.8%) and Mycobacterium africanum (M. africanum) (1.2%) respectively. We did not detect any M. bovis. Comparative analyses using spoligotyping revealed that the majority of isolates belong to major clades of M. tuberculosis: Haarlem (7.6%), Latin American-Mediterranean (34.4%) and T clade (26.7%); the remaining isolates (31.3%) where distributed among the minor clades. The predominant group of isolates (34.4%) corresponded to spoligotype 61, previously described as the “Cameroon family. Further analysis based on MIRU-VNTR profiles had greater resolving power than spoligotyping and defined additional genotypes in the same spoligotype cluster.

Conclusion
The molecular characterization of MTBC strains from humans in two ecological regions of Cameroon has shown that M. tuberculosis sensu stricto is the predominant agent of TB cases in the zones. Three decades ago, TB was reported to be caused by M. africanum in 56.0% of cases. The present findings are consistent with a major shift in the prevalence of M. tuberculosis in Cameroon.
A new mutation in the gene encoding mitochondrial seryl-tRNA synthetase as a cause of HUPRA syndrome
Authors: Rivera Henry , Martín-Hernández Elena , Delmiro Aitor , García-Silva María Teresa , Quijada-Fraile Pilar , Muley Rafael , Arenas Joaquín , Martín Miguel A , Martínez-Azorín Francisco 
Published: September 2013

Abstract

Background
HUPRA syndrome is a rare mitochondrial disease characterized by hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis. This syndrome was previously described in three patients with a homozygous mutation c.1169A > G (p.D390G) in SARS2, encoding the mitochondrial seryl-tRNA synthetase.

Case presentation
Here we report the clinical and genetic findings in a girl and her brother. Both patients were clinically diagnosed with the HUPRA syndrome. Analysis of the pedigree identified a new homozygous mutation c.1205G > A (p.R402H) in SARS2 gene. This mutation is very rare in the population and it is located at the C-terminal globular domain of the homodimeric enzyme very close to p.D390G.

Conclusion
Several data support that p.R402H mutation in SARS2 is a new cause of HUPRA syndrome.
Evaluation of the immune factors in the tumor environment before and after the treatment of cetuximab combined with chemotherapy
Authors: Zhu Yanyun , Li Jie , Jing Fangfang , Ji Tiefeng , Guo Xiaoqin , Yang Junlan , Jiao Shunchang 
Published: September 2013

Abstract

Background
The effect of chemotherapy combined with monoclonal antibodies (mAbs) on the immune state of the tumor environment remains unclear and controversial. The aim of this study is to examine the effect of chemotherapy combined with cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and the correlation of that effect and the clinical efficacy.

Methods
Twelve patients with colorectal cancer, who received the treatment of chemotherapy combined with C225, were enrolled in this study. The tumor specimen of the primary colorectal cancer before and after treatment was obtained. The expression of a series of immune factors (TGF-β1, CD8, IL-2, TNF-α, and VEGF) was measured by immunochemistry. The expression of these immune factors before and after treatment was compared by the Wilcoxon signed-rank test. The correlation of the change of immune parameter expression after treatment and clinical efficacy was examined by chi-square tests. The correlation of the expression of immune factors, clinical efficacy, and treatment number was examined by the Spearman’s correlation analysis.

Results
There was no significant difference between the expression of TGF-β1 before and after the treatment (P >0.05). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-α, there were no significant differences between the expression before and after the treatment (P >0.05), and the change of expression after treatment also did not correlate significantly with clinical efficacy (P >0.05). The change of IL-2 expression after treatment significantly correlated negatively with treatment number (correlation coefficient = -0.585, P = 0.046). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression of TNF-α significantly correlated positively with the expression of IL-2 (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of TGF-β1 significantly correlated negatively with the expression of CD8 (correlation coefficient = -0.664, P = 0.019).

Conclusions
These results suggested that, in the tumor environment, the change of immune factors after treatment of cetuximab combined with chemotherapy may be associated with clinical efficacy.
rAAV-mediated overexpression of TGF-β stably restructures human osteoarthritic articular cartilage in situ
Authors: Venkatesan Jagadeesh K , Rey-Rico Ana , Schmitt Gertrud , Wezel Anna , Madry Henning , Cucchiarini Magali 
Published: September 2013

AbstractBackgroundTherapeutic gene transfer is of significant value to elaborate efficient, durable treatments against human osteoarthritis (OA), a slow, progressive, and irreversible disorder for which there is no cure to date.MethodsHere, we directly applied a recombinant adeno-associated virus (rAAV) vector carrying a human transforming growth factor beta (TGF-β) gene sequence to primary human normal and OA chondrocytesin vitroand cartilage explantsin situto monitor the stability of transgene expression and the effects of the candidate pleiotropic factor upon the regenerative cellular activities over time.ResultsEfficient, prolonged expression of TGF-β achieved via rAAV gene transfer enhanced both the proliferative, survival, and anabolic activities of cells over extended periods of time in all the systems evaluated (at least for 21 daysin vitroand for up to 90 daysin situ) compared with control (reporter) vector delivery, especiallyin situwhere rAAV-hTGF-β allowed for a durable remodeling of OA cartilage. Notably, sustained rAAV production of TGF-β in OA cartilage advantageously reduced the expression of key OA-associated markers of chondrocyte hypertrophic and terminal differentiation (type-X collagen, MMP-13, PTHrP, β-catenin) while increasing that of protective TIMPs and of the TGF-β receptor I in a manner that restored a favorable ALK1/ALK5 balance. Of note, the levels of activities in TGF-β-treated OA cartilage were higher than those of normal cartilage, suggesting that further optimization of the candidate treatment (dose, duration, localization, presence of modulating co-factors) will most likely be necessary to reproduce an original cartilage surface in relevant models of experimental OAin vivowithout triggering potentially adverse effects.ConclusionsThe present findings show the ability of rAAV-mediated TGF-β gene transfer to directly remodel human OA cartilage by activating the biological, reparative activities and by regulating hypertrophy and terminal differentiation in damaged chondrocytes as a potential treatment for OA or for other disorders of the cartilage that may require transplantation of engineered cells.
New microarchitectures of (Er,Yb):Lu2O3 nanocrystals embedded in PMMA: synthesis, structural characterization, and luminescent properties
Authors: Galceran Montserrat , Pujol Maria Cinta , Carvajal Joan Josep , Mateos Xavier , Formentín Pilar , Pallarès Josep , Marsal Lluis Francesc , Park Kyung Ho , Rotermund Fabian , Kim Kihong , Aguiló Magdalena , Díaz Francesc 
Published: September 2013

Abstract
We report the formation of two-dimensional disordered arrays of poly(methyl)methacrylate (PMMA) microcolumns with embedded single size distribution of Lu0.990Er0.520Yb0.490 nanocrystals, (Er,Yb):Lu2O3, using a disordered porous silicon template. The cubic (Er,Yb):Lu2O3 nanocrystals, which crystallize into the cubic system with

Ia

3
¯

space group, were synthesized using the modified Pechini method. Electronic microscopic techniques were used to study the distribution of the nanocrystals in the PMMA columns. Cathodoluminescence was used to observe the visible luminescence of the particles. Red emission attributed to 4 F9/2 → 4I15/2 erbium transition is predominant in these new composites.