bluuebunny/crossref_metadata_2025_split huggingface dataset:
Langmuir Circulation: An Agent for Vertical Restratification?
Authors: Li Ke , Zhang Zhexuan , Chini Greg , Flierl Glenn 
Published: June 2012

Abstract
Comparably little is known about the impact of down-front-propagating surface waves on the stability of submesoscale lateral fronts in the ocean surface mixed layer. In this investigation, the stability of lateral fronts in gradient–wind balance to two-dimensional (down-front invariant) disturbances is analyzed using the stratified, rotating Craik–Leibovich (CL) equations. Through the action of the CL vortex force, the surface waves fundamentally alter the superinertial, two-dimensional linear stability of these fronts, with the classical symmetric instability mode being replaced by a hybrid Langmuir circulation/symmetric mode. The hybrid mode is shown to exhibit much larger growth rates than the pure symmetric mode, to exist in a regime in which the vertical Richardson number is greater than 1, and to accomplish significant cross-isopycnal transport. Nonhydrostatic numerical simulations reveal that the nonlinear evolution of this hybrid instability mode can lead to rapid, that is, superinertial, vertical restratification of the mixed layer. Paradoxically, Langmuir circulation—generally viewed as a prominent vertical mixing mechanism in the upper ocean—may thus play a role in mixed layer restratification.
Interdisciplinary Climate: The Case of the First 50 Years of British Observations in Australia
Authors: McGuffie Kendal , Henderson-Sellers Ann 
Published: June 2012

Abstract
This paper presents the case for improved interdisciplinarity in climate research in the context of assessing and discussing the caution required when utilizing some types of historical climate data. This is done by a case study examining the reliability of the instruments used for collecting weather data in Australia between 1788 and 1840, as well as the observers themselves, during the British settlement of New South Wales. This period is challenging because the instruments were not uniformly calibrated and were created, repaired, and used by a wide variety of people with skills that frequently remain undocumented. Continuing significant efforts to rescue such early instrumental records of climate are likely to be enhanced by more open, interdisciplinary research that encourages discussion of an apparent dichotomy of view about the quantitative value of early single-instrument data between historians of physics (including museum curators) and climate researchers.
Causal inference with a quantitative exposure
Authors: Zhang Zhiwei , Zhou Jie , Cao Weihua , Zhang Jun 
Published: June 2012

Summary The current statistical literature on causal inference is mostly concerned with binary or categorical exposures, even though exposures of a quantitative nature are frequently encountered in epidemiologic research. In this article, we review the available methods for estimating the dose–response curve for a quantitative exposure, which include ordinary regression based on an outcome regression model, inverse propensity weighting and stratification based on a propensity function model, and an augmented inverse propensity weighting method that is doubly robust with respect to the two models. We note that an outcome regression model often imposes an implicit constraint on the dose–response curve, and propose a flexible modeling strategy that avoids constraining the dose–response curve. We also propose two new methods: a weighted regression method that combines ordinary regression with inverse propensity weighting and a stratified regression method that combines ordinary regression with stratification. The proposed methods are similar to the augmented inverse propensity weighting method in the sense of double robustness, but easier to implement and more generally applicable. The methods are illustrated with an obstetric example and compared in simulation studies.
Sonic hedgehog pathway expression in non-small cell lung cancer
Authors: Savani Malvi , Guo Yan , Carbone David P. , Csiki Ildiko 
Published: June 2012

Objective: Activation of the hedgehog pathway is an important signaling mechanism crucial in embryogenesis and has strong links to carcinogenesis. This study investigates the expression of the Sonic hedgehog pathway molecules in non-small cell lung tumors as it relates to clinical outcome of various non-small cell lung cancers. Methods: A tissue microarray with 81 samples from 42 patients with various non-small cell lung cancer histologies was examined without the aid of laser microdissection. All samples were stained with antibodies directed against Sonic hedgehog, Ptch-1, Smoothened, and Gli-1. Results: Most of the tumor samples showed negative to weak expression of the pathway proteins (Sonic hedgehog, 38% negative to 20% weak; Ptch-1, 100% negative; Smoothened, 69% negative to 7% weak; Gli-1, 57% negative to 5% weak) compared with higher expression in normal lung epithelial cells. Conclusion: The same pathway expression did not correlate with clinical outcome. While our results do not provide any indication that the pathway molecules are correlated to overall patient survival possibly due to the limited sample size, our study shows minimum overexpression of Sonic hedgehog pathway in non-small cell lung cancer and this did not correlate clinically with patient outcome.
The role of biologic agents in damage progression in rheumatoid arthritis: indirect comparison of data coming from randomized clinical trials
Authors: Favalli Ennio Giulio , Pregnolato Francesca , Biggioggero Martina , Meroni Pier Luigi 
Published: June 2012

Objectives: All biologic agents approved for the treatment of rheumatoid arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage progression in several randomized clinical trials (RCTs), but direct head-to-head comparisons have never been conducted. The purpose of this investigation is to analyse data coming from main RA RCTs and to perform an indirect comparison. Methods: A systematic review of literature from 1988 to 2011 was conducted. Only randomized, double-blind, controlled, comparative trials, with evaluation of radiographic progression were included. The radiographic score was standardized and mean difference in the percentage of the annual radiographic progression rate was used as the effect measure. Heterogeneity between studies was estimated by I2 test. For each trial, the effect was plotted according to its standard error in a funnel plot. Results: Of 44 potentially relevant trials, 12 RCTs were included in the study. In order to optimize RCTs comparison, studies were stratified in early and late RA group. Main population characteristics were similar in both early and late RA groups, whereas the standardized baseline radiographic score value significantly differs among trials in both early (range 2.7–21.9) and late (range 23.46–75) RA groups. The standardized annual estimated progression is similar across the late RA group. Strong evidence of heterogeneity ( I2 = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the early RA group. Total mean difference was −16.28 (95% confidence interval [CI] −24.42 to −8.14). For the late RA group a random model was used ( I2 = 99%, p = 0.00001) and a total mean difference of −39.25 (95% CI −53.77 to −24.73) was found. Conclusions: All biologic agents provide a favourable effect on disease progression both in early and late RA. The significant heterogeneity among various RCTs did not allow an effective comparison of the performance of biologic agents in each study.
Human regulatory T cells induce T-lymphocyte senescence
Authors: Ye Jian , Huang Xingxu , Hsueh Eddy C. , Zhang Qunyuan , Ma Chunling , Zhang Yanping , Varvares Mark A. , Hoft Daniel F. , Peng Guangyong 
Published: June 2012

Abstract
Regulatory T (Treg) cells have broad suppressive activity on host immunity, but the fate and function of suppressed responder T cells remains largely unknown. In the present study, we report that human Treg cells can induce senescence in responder naive and effector T cells in vitro and in vivo. Senescent responder T cells induced by human Treg cells changed their phenotypes and cytokine profiles and had potent suppressive function. Furthermore, Treg-mediated molecular control of senescence in responder T cells was associated with selective modulation of p38 and ERK1/2 signaling and cell-cycle–regulatory molecules p16, p21, and p53. We further revealed that human Treg-induced senescence and suppressor function could be blocked by TLR8 signaling and/or by specific ERK1/2 and p38 inhibition in vitro and in vivo in animal models. The results of the present study identify a novel mechanism of human Treg cell suppression that induces targeted responder T-cell senescence and provide new insights relevant for the development of strategies capable of preventing and/or reversing Treg-induced immune suppression.
Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery
Authors: Tanaka Takayuki , Takahashi Kazutoshi , Yamane Mayu , Tomida Shota , Nakamura Saori , Oshima Koichi , Niwa Akira , Nishikomori Ryuta , Kambe Naotomo , Hara Hideki , Mitsuyama Masao , Morone Nobuhiro , Heuser John E. , Yamamoto Takuya , Watanabe Akira , Sato-Otsubo Aiko , Ogawa Seishi , Asaka Isao , Heike Toshio , Yamanaka Shinya , Nakahata Tatsutoshi , Saito Megumu K. 
Published: June 2012

Abstract
Chronic infantile neurologic cutaneous and articular (CINCA) syndrome is an IL-1–driven autoinflammatory disorder caused mainly by NLRP3 mutations. The pathogenesis of CINCA syndrome patients who carry NLRP3 mutations as somatic mosaicism has not been precisely described because of the difficulty in separating individual cells based on the presence or absence of the mutation. Here we report the generation of NLRP3-mutant and nonmutant-induced pluripotent stem cell (iPSC) lines from 2 CINCA syndrome patients with somatic mosaicism, and describe their differentiation into macrophages (iPS-MPs). We found that mutant cells are predominantly responsible for the pathogenesis in these mosaic patients because only mutant iPS-MPs showed the disease relevant phenotype of abnormal IL-1β secretion. We also confirmed that the existing anti-inflammatory compounds inhibited the abnormal IL-1β secretion, indicating that mutant iPS-MPs are applicable for drug screening for CINCA syndrome and other NLRP3-related inflammatory conditions. Our results illustrate that patient-derived iPSCs are useful for dissecting somatic mosaicism and that NLRP3-mutant iPSCs can provide a valuable platform for drug discovery for multiple NLRP3-related disorders.
Case-cohort design in practice – experiences from the MORGAM Project
Authors: Kulathinal Sangita , Karvanen Juha , Saarela Olli , Kuulasmaa Kari ,   the MORGAM Project
Published: June 2012

AbstractWhen carefully planned and analysed, the case-cohort design is a powerful choice for follow-up studies with multiple event types of interest. While the literature is rich with analysis methods for case-cohort data, little is written about the designing of a case-cohort study. Our experiences in designing, coordinating and analysing the MORGAM case-cohort study are potentially useful for other studies with similar characteristics. The motivation for using the case-cohort design in the MORGAM genetic study is discussed and issues relevant to its planning and analysis are studied. We propose solutions for appending the earlier case-cohort selection after an extension of the follow-up period and for achieving maximum overlap between earlier designs and the case-cohort design. Approaches for statistical analysis are studied in a simulation example based on the MORGAM data.
Spontaneous chiral symmetry breaking in early molecular networks
Authors: Kafri Ran , Markovitch Omer , Lancet Doron 
Published: June 2012

AbstractBackgroundAn important facet of early biological evolution is the selection of chiral enantiomers for molecules such as amino acids and sugars. The origin of this symmetry breaking is a long-standing question in molecular evolution. Previous models addressing this question include particular kinetic properties such as autocatalysis or negative cross catalysis.ResultsWe propose here a more general kinetic formalism for early enantioselection, based on our previously described Graded Autocatalysis Replication Domain (GARD) model for prebiotic evolution in molecular assemblies. This model is adapted here to the case of chiral molecules by applying symmetry constraints to mutual molecular recognition within the assembly. The ensuing dynamics shows spontaneous chiral symmetry breaking, with transitions towards stationary compositional states (composomes) enriched with one of the two enantiomers for some of the constituent molecule types. Furthermore, one or the other of the two antipodal compositional states of the assembly also shows time-dependent selection.ConclusionIt follows that chiral selection may be an emergent consequence of early catalytic molecular networks rather than a prerequisite for the initiation of primeval life processes. Elaborations of this model could help explain the prevalent chiral homogeneity in present-day living cells.ReviewersThis article was reviewed by Boris Rubinstein (nominated by Arcady Mushegian), Arcady Mushegian, Meir Lahav (nominated by Yitzhak Pilpel) and Sergei Maslov.
Epigenetic imprinting by commensal probiotics inhibits the IL-23/IL-17 axis in an in vitro model of the intestinal mucosal immune system
Authors: Ghadimi Darab , Helwig Ulf , Schrezenmeir Juergen , Heller Knut J , de Vrese Michael 
Published: June 2012

Abstract
Lactic acid bacteria inhibits NFκB-mediated transcriptional activation of IBD causing factors (IL-23/IL-17/CD40) by reducing histone acetylation while enhancing DNA methylation.
The pathophysiology of IBD is characterized by a complex interaction between genes and the environment. Genetic and environmental differences are attributed to the heterogeneity of the disease pathway and to the epigenetic modifications that lead to altered gene expression in the diseased tissues. The epigenetic machinery consists of short interfering RNA, histone modifications, and DNA methylation. We evaluated the effects of Bifidobacterium breve (DSMZ 20213) and LGG (ATCC 53103), as representatives of commensal probiotics on the expression of IL-17 and IL-23, which play an important role in IBD, and on the epigenetic machinery in a 3D coculture model composed of human intestinal HT-29/B6 or T84 cells and PBMCs. The cells were treated with LPS in the presence or absence of bacteria for 48 h, and the expression of IL-17, IL-23, and CD40 at the mRNA and protein levels was assessed using TaqMan qRT-PCR and ELISA, respectively. Western blotting was used to assess the expression of the MyD88, the degradation of IRAK-1 and IκBα, the expression of the NF-κB p50/p65 subunits, the p-p38 MAPK and p-MEK1, as well as histone modifications. NF-κB activity was assessed by NF-κB-dependent luciferase reporter gene assays. The accumulation of Ac-H4 and DNA methylation was quantitatively assessed using colorimetric assays. B. breve and LGG diminished the LPS-induced expression of IL-17, IL-23, CD40, and histone acetylation, while slightly enhancing DNA methylation. These effects were paralleled by a decrease in the nuclear translocation of NF-κB, as demonstrated by a decrease in the expression of MyD88, degradation of IRAK-1 and IκBα expression of the nuclear NF-κB p50/p65 subunits, p-p38 MAPK and p-MEK1, and NF-κB-dependent luciferase reporter gene activity in LPS-stimulated cells. B. breve and LGG may exert their anti-inflammatory effects in the gut by down-regulating the expression of the IBD-causing factors (IL-23/IL-17/CD40) associated with epigenetic processes involving the inhibition of histone acetylation and the optimal enhancement of DNA methylation, reflected in the limited access of NF-κB to gene promoters and reduced NF-κB-mediated transcriptional activation. We describe a new regulatory mechanism in which commensal probiotics inhibit the NF-κB-mediated transcriptional activation of IBD-causing factors (IL-23/IL-17/CD40), thereby simultaneously reducing histone acetylation and enhancing DNA methylation.
Surfactant-free Synthesis and Formation Mechanism of Fe3O4 Nanospheres in Mixed Solvent Ethylene Glycol–Water System
Authors: Xu Yanyan , Cao Yanyan , Sun Yaqiu , Zhang Guoying , Gao Dongzhao 
Published: June 2012

Abstract
Uniform Fe3O4 nanospheres have been synthesized by a simple ethylene glycol–H2O system without adding any additives. The average diameter of the Fe3O4 nanospheres was 120–190 nm, and the nanospheres are formed by nanoparticles of several tens of nanometers. The presence of a certain amount of deionized water and the controlled reaction temperature plays an important role in the formation of the Fe3O4 nanospheres. The formation mechanism of the nanospheres is discussed on the basis of the experimental results.
One-pot Chemoenzymatic Route to Chitoheptaose via Specific Transglycosylation of Chitopentaose–Oxazoline on Chitinase-template
Authors: Yoshida Naoki , Tanaka Tomonari , Noguchi Masato , Kobayashi Atsushi , Ishikura Kumiko , Ikenuma Tatsuya , Seno Hiromu , Watanabe Takeshi , Kohri Michinari , Shoda Shin-ichiro 
Published: June 2012

Abstract
One-pot regio- and stereospecific synthesis of chitoheptaose ((GlcNAc)7) has been achieved by using chitopentaose ((GlcNAc)5) and chitobiose ((GlcNAc)2) as starting materials. The key intermediate, 1,2-oxazoline derivative of (GlcNAc)5, could be directly prepared in water and successfully transglycosylated to (GlcNAc)2 catalyzed by a mutant chitinase with lower hydrolyzing activity.
Assessment of total phenols and extractives of mahogany wood by near infrared spectroscopy (NIRS)
Authors: da Silva Allan Ribeiro , Monteiro Pastore Tereza Cristina , Batista Braga Jez Willian , Davrieux Fabrice , Arakaki Okino Esmeralda Yoshico , Rauber Coradin Vera Teresinha , Alves Camargos José Arlete , do Prado Alexandre Gustavo Soares 
Published: June 2012

Abstract
The resistance to decomposition of mahogany wood (Sweitenia macrophylla King) ranges from high to moderate level. Wood extractives, mainly due to the presence of phenol compounds are related to the natural durability of wood. The technique of near infrared spectroscopy (NIRS) coupled with multivariate analysis has been applied to assess the extractives and phenols of 41 samples of mahogany in powder form. The hot water-soluble extractives were quantitatively determined, and total phenol content was measured with the Folin-Denis colourimetric reagent. Models were developed with the NIRS data for each of the two variables. The results indicated that NIRS can be a useful tool to a rapid evaluation of the extractive contents and total phenolic compounds of mahogany wood. The method was able to predict the interesting properties with errors lower than 10% (w/w) and had the capability of detecting samples that have a minimum concentration of 2.4% (w/w) of extractives and total phenolic compounds, respectively.
Reproducibility of Newly Developed Spinal Topography Measurements for Scoliosis
Authors: Rankine Leah , Liu Xue C , Tassone Channing , Lyon Roger , Tarima Sergey , Thometz John 
Published: June 2012

Objective:
In an effort to limit exposure to ionizing radiation and fully characterize three dimensional changes in the spine of patients with scoliosis reliable non-invasive methods of spinal back contour analysis (Milwaukee Topographic Scanner) (MTS) have been developed.

Study Design:
The current study compares spinal topography measurements among different subject positions and evaluates the reproducibility of the system for both inter-rater and intra-rater reliability.

Methods:
A dummy cast (plastic cast) of one patient with adolescent idiopathic scoliosis was created in order to test the reliability of the MTS. The dummy cast was positioned and rotated in 3D while scanned by two investigators using the MTS. A total of twelve parameters including Q-angle (an analog to X-ray’s Cobb angle) were extracted.

Results:
All measurements of intra-rater and inter-rater reliability were excellent (Intraclass Correlation Coefficients ranging from 0.89 to 0.99) with the exception of Pelvic Tilt (intra-rater ICC is 0.61) and lordosis angle (inter-rater ICC is 0.82). No significant variability among investigators was observed for all tested metrics. No significant variability due to position was observed for the majority of back contour measurements but there were significant changes in the T1-S1 angle, T1-S1 deviation, T1-NC angle, T1-NC deviation, and Back Height metric (p< 0.05).

Conclusions:
The MTS is a reliable method of raster stereography in the measurement of the back contour, which will help monitor the progression of children with idiopathic scoliosis and reduce the use of X-rays.
Diabetic Ketoacidosis at Diagnosis Influences Complete Remission After Treatment With Hematopoietic Stem Cell Transplantation in Adolescents With Type 1 Diabetes
Authors: Gu Weiqiong , Hu Jiong , Wang Weiqing , Li Lirong , Tang Wei , Sun Shouyue , Cui Weijuan , Ye Lei , Zhang Yifei , Hong Jie , Zhu Dalong , Ning Guang 
Published: June 2012

OBJECTIVE
To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis.

RESEARCH DESIGN AND METHODS
We enrolled 28 patients with type 1 diabetes, aged 14–30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA1c, C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT.

RESULTS
After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (Cmax), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P &lt; 0.05). In the DKA group, significant elevation of fasting C-peptide levels and Cmax levels was observed only at 18 and 6 months, respectively. There was no mortality.

CONCLUSIONS
We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.