A large oxygen-dominated core from the seismic cartography of a pulsating white dwarf.

White-dwarf stars are the end product of stellar evolution for most stars in the Universe. Their interiors bear the imprint of fundamental mechanisms that occur during stellar evolution. Moreover, they are important chronometers for dating galactic stellar populations, and their mergers with other white dwarfs now appear to be responsible for producing the type Ia supernovae that are used as standard cosmological candles. However, the internal structure of white-dwarf stars-in particular their oxygen content and the stratification of their cores-is still poorly known, because of remaining uncertainties in the physics involved in stellar modelling codes. Here we report a measurement of the radial chemical stratification (of oxygen, carbon and helium) in the hydrogen-deficient white-dwarf star KIC08626021 (J192904.6+444708), independently of stellar-evolution calculations. We use archival data coupled with asteroseismic sounding techniques to determine the internal constitution of this star. We find that the oxygen content and extent of its core exceed the predictions of existing models of stellar evolution. The central homogeneous core has a mass of 0.45 solar masses, and is composed of about 86 per cent oxygen by mass. These values are respectively 40 per cent and 15 per cent greater than those expected from typical white-dwarf models. These findings challenge present theories of stellar evolution and their constitutive physics, and open up an avenue for calibrating white-dwarf cosmochronology.

Development and validation of new diagnostic criteria for atopic dermatitis in children of China.

BACKGROUND: In previous epidemiological study, the prevalence of atopic dermatitis (AD) was 12.94% among children aged 1-7 years by clinical diagnosis, whereas that was 4.76% and 3.51% using U.K., and Hanifin and Rajka diagnostic criteria. OBJECTIVE: We aimed to propose new diagnostic criteria for children and evaluate its efficiency in different populations. METHODS: We screened atopic features and analysed their correlation with AD using data from a previous study. A new set of diagnostic criteria for children in China was proposed and validated in 1031 children in outpatient clinics and 538 children in a birth cohort survey. Clinical diagnosis and atopic feature evaluation were performed face to face by dermatologists specialized in AD. Three criteria were compared for diagnostic efficiency using the clinical diagnosis as the reference. RESULTS: The new diagnostic criteria for children were based on (i) pruritus; (ii) 'typical morphology and distribution' or 'atypical morphology and distribution with xerosis'; and (iii) a chronic or chronically relapsing course. Compared to classical diagnostic criteria, the sensitivity of the new diagnostic criteria was significantly higher in the epidemiological survey and the clinical setting, especially obvious among mild and moderate AD. In the birth cohort, the new criteria showed similar sensitivity and specificity. CONCLUSION: The new criteria for children yielded higher sensitivity for the diagnosis of AD in the epidemiological survey and clinical setting, particularly for mild and moderate AD. Among the birth cohort with a complete medical history, three criteria showed similar sensitivity and specificity.

Gut microbiota and obesity-associated osteoarthritis.

Obesity is a well-known primary risk factor for osteoarthritis (OA). In recent decades, the biomechanics-based theoretical paradigm for the pathogenesis of obesity-associated OA has been gradually but fundamentally modified. This modification is a result of accumulating evidence that biological factors also contribute to the etiology of the disease. The gut microbiota is a complicated ecosystem that profoundly influences the health of the host and can be modulated by the combined effects of environmental stimuli and genetic factors. Recently, enteric dysbacteriosis has been identified as a causal factor in the initiation and propagation of obesity-associated OA in animal models. Gut microbes and their components, microbe-associated lipid metabolites, and OA interact at both systemic and local levels through mechanisms that involve interplay with the innate immune system. However, the demonstration of causality in humans will require further studies. Nonetheless, probiotics, prebiotics, dietary habits and exercise, which aid the restoration of a healthy microbial community, are potential therapeutic approaches in the treatment of obesity-associated OA.

Diffraction effect and its elimination method for diamond-turned optics.

In the visible light band, the diffraction effect of a diamond-turned surface will cause the optical performance to heavily deteriorate. Due to the insufficient understanding of diffraction effect, post-treatment, such as polishing technology has to be fulfilled. To reveal the origins of diffraction effect of the diamond-turned surface under visible light, theoretical analyses are carried out with consideration of the influencing factors in diamond turning. Simulation results, coupled with experimental observations, demonstrate that the periodic components of surface roughness are responsible for the diffraction light distribution in the horizontal direction of the receiving screen. However, the aperiodic components of surface roughness, derived from defects in material matrix, result in the diffraction spots on the whole receiving screen. To directly eliminate the diffraction effect in diamond turning, a novel method-with control on tool edge quality, material defects, and processing parameters-is proposed. The measurement results prove the effectiveness of this method, and the diffraction-free surface finish without any post-treatment is successfully acquired.

Influence of multifrequency vibration on the optical performance of diamond-turned optics and its elimination method.

In this work, to reveal the underlying mechanism of the influence of multifrequency vibration on the optical performance of diamond-turned optics, a systematic simulation investigation is performed using Fourier modal method and fast Fourier transformation based on a well-established surface topography model. Both the simulation results and the experimental observations demonstrate that the center area is the most heavily influenced region on the machined surface, which is closely associated with the distribution of the surface roughness under multifrequency vibration. The vibration amplitude has a visible impact on the specular reflectivity, and with an increase in vibration amplitude, the specular reflectivity in the center area obviously decreases, while the specular reflectivity in remote areas basically remains invariant. To eliminate the negative effect in relation to the vibration, a two-step process technology is developed that includes a strict spindle balance and the optimization of process parameters, particularly the depth of cut and the spindle speed. The cutting experiments further validate the effectiveness of the proposed technology for elimination of the negative effect concerning multifrequency vibration.

Influence of tool edge waviness on the diffraction effect of diamond-turned optics: theoretical simulation and experimental validation.

In this work, the influence of tool edge waviness on the diffraction effect of diamond-turned optics is simulated theoretically and further validated experimentally. In simulation, a 3D surface topography model with consideration of the influence of tool edge waviness is established, in which the variation of tool edge profile is estimated by a linear model in relation to the cutting distance. The results show that the diffraction effect represented in simulation is consistent with the experimental observation. With the deterioration of tool edge waviness, the diffraction efficiency of the specular light decreases, but the high-order diffracted light intensively distributes in the horizontal direction on the receiving screen. Such observation can be attributed to the subgrating effect induced by the periodic duplication of the tool edge profile on the machined surface, which heavily depends on the deterioration of tool edge waviness. Finally, a waviness-controlled diamond tool is recommended to finish a diffraction-free optics by the diamond turning process. Moreover, the diffraction effect can also be employed to monitor the dynamic wear of the cutting tool in diamond turning.

Phenotypic analysis of atopic dermatitis in children aged 1-12 months: elaboration of novel diagnostic criteria for infants in China and estimation of prevalence.

BACKGROUND: Atopic dermatitis (AD) is the most common skin disorder in infancy. However, the diagnosis and definite significance of infantile AD remains a debated issue. OBJECTIVE: To analyse the phenotypes of AD in infancy, to establish diagnostic criteria and to estimate the prevalence of this condition in China. METHODS: This is a multicentric study, in which 12 locations were chosen from different metropolitan areas of China. Following careful and complete history-taking and skin examination, the definite diagnosis of AD was made and the severity based on the SCORAD index was determined by local experienced dermatologists. Based on the detailed phenotyping, the major and representative clinical features of infantile AD were selected to establish the diagnostic criteria and evaluate their diagnostic efficacy. RESULTS: A total of 5967 infants were included in this study. The overall point prevalence of AD was 30.48%. The infantile AD developed as early as at the second month of life, and its incidence peaked in the third month of life at 40.81%. The proportion of mild, moderate and severe AD was 67.40%, 30.57% and 2.03%, respectively. The most commonly seen manifestations in the infantile AD were facial dermatitis (72.07%), xerosis (42.72%) and scalp dermatitis (27.93%). We established the novel diagnostic criteria of infants, which included: (i) onset after 2 weeks of birth; (ii) pruritus and/or irritability and sleeplessness comparable with lesions; and (iii) all two items above with one of the following items can reach a diagnosis of AD: (i) eczematous lesions distributed on cheeks and/or scalp and/or extensor limbs, and (ii) eczematous lesions on any other parts of body accompanied by xerosis. CONCLUSIONS: In China, the prevalence of AD in infancy is 30.48% according to clinical diagnosis of dermatologists. The novel Chinese diagnostic criteria for AD in infants show a higher sensitivity and comparable specificity.

Evaluation of back scatter interferometry, a method for detecting protein binding in solution.

Back Scatter Interferometry (BSI) has been proposed to be a highly sensitive and versatile refractive index sensor usable for analytical detection of biomarker and protein interactions in solution. However the existing literature on BSI lacks a physical explanation of why protein interactions in general should contribute to the BSI signal. We have established a BSI system to investigate this subject in further detail. We contribute with a thorough analysis of the robustness of the sensor including unwanted contributions to the interferometric signal caused by temperature variation and dissolved gasses. We report a limit of the effective minimum detectability of refractive index at the 10(-7) level. Long term stability was examined by simultaneously monitoring the temperature inside the capillary revealing an average drift of 2.0 × 10(-7) per hour. Finally we show that measurements on protein A incubated with immunoglobulin G do not result in a signal that can be attributed to binding affinities as otherwise claimed in literature.

Contribution of visceral fat accumulation to carotid intima-media thickness in a Chinese population.

OBJECTIVE: Recent observational studies have reported that body fat distribution might be differentially associated with subclinical atherosclerosis. We previously reported that visceral fat area (VFA) ≥ 80 cm2 is the optimal cutoff for identifying abdominal obesity in Chinese subjects. We examined whether VFA ≥ 80 cm2 reflects the association between abdominal obesity and subclinical atherosclerosis, and if determination of the visceral fat quantity is useful for assessing subclinical atherosclerosis in asymptomatic individuals. METHODS AND RESULTS: Participants (N=1005, men 515, women 490, 34-66 years) free of cardiovascular disease underwent magnetic resonance imaging and carotid ultrasound assessment to quantify VFA and carotid intima-media thickness (C-IMT). Overweight/obese subjects (body mass index (BMI) ≥ 25.0 kg m(-2)) had a higher C-IMT than lean subjects (BMI <25.0 kg m(-2)) (P<0.01). Subjects with VFA ≥ 80 cm2 had significantly higher C-IMT than those without abdominal obesity regardless of BMI (P<0.01). By multivariate regression analysis adjusted for anthropometric measurements and cardiovascular risk factors, waist circumference but not BMI was independently correlated with C-IMT in men (P<0.001). Similar findings were observed with an accurate obesity indices adjusted model, which showed that VFA was an independent risk factor for increased C-IMT in men but not in women. CONCLUSIONS: VFA 80 cm2 effectively identified carotid atherosclerosis for both lean and obese individuals in middle-aged Chinese men.

Increment of 30-min post-challenge plasma glucose is associated with urine albumin excretion in men with normal glucose regulation.

AIMS: The overwhelming majority of subjects with normal glucose regulation have the highest plasma glucose concentration at 30 minutes during oral glucose tolerance. We aimed to examine the association between increment of 30-min post-challenge glucose and albuminuria in participants with normal glucose regulation. METHODS: A population-based cross-sectional study was conducted in six communities in Shanghai between 2007 and 2008. A total of 3508 subjects with normal glucose regulation had complete data and were enrolled into the analysis. Among the selected subjects, only 1525 individuals (581 men, 944 women) were examined for their serum insulin levels. We assessed post-challenge blood glucose and insulin at 0, 30 and 120 min, urinary albumin and creatinine. The 30-min post-challenge glucose increment (Δ) was calculated as 30-min post-challenge glucose minus fasting plasma glucose, and albumin/creatinine ratio was used to reflect urinary albumin excretion. RESULTS: Multivariable logistic regression analysis revealed that the Δ30-min post-challenge glucose was independently associated with increased albumin/creatinine ratio in men with normal glucose regulation (OR = 1.08, P = 0.025), but not in women. Furthermore, multivariable linear regression analysis revealed that early-phase glucose disposition index was the main factor responsible for Δ30-min post-challenge glucose and explained 14-20% of the variance of Δ30-min post-challenge glucose in the two subgroups (P < 0.05). Notably, men had higher Δ30-min post-challenge glucose and lower early-phase glucose disposition index than women (all P < 0.001). CONCLUSIONS: The 30-min post-challenge plasma glucose increment is associated with urine albumin excretion in men with normal glucose regulation.

Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.

Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.

Expression and Solution NMR Study of Multi-site Phosphomimetic Mutant BCL-2 Protein.

BACKGROUND: The significance of multi-site phosphorylation of BCL-2 protein in the flexible loop domain remains controversial, in part due to the lack of structural biology studies of phosphorylated BCL-2. OBJECTIVE: The purpose of the study is to explore the phosphorylation induced structural changes of BCL-2 protein. METHODS: We constructed a phosphomietic mutant BCL-2(62-206) (t69e, s70e and s87e) (EEEBCL- 2-EK (62-206)), in which the BH4 domain and the part of loop region was truncated (residues 2-61) to enable a backbone resonance assignment. The phosphorylation-induced structural change was visualized by overlapping a well dispersed 15N-1H heteronuclear single quantum coherence (HSQC) NMR spectroscopy between EEE-BCL-2-EK (62-206) and BCL-2. RESULTS: The EEE-BCL-2-EK (62-206) protein reproduced the biochemical and cellular activity of the native phosphorylated BCL-2 (pBCL-2), which was distinct from non-phosphorylated BCL-2 (npBCL-2) protein. Some residues in BH3 binding groove occurred chemical shift in the EEEBCL- 2-EK (62-206) spectrum, indicating that the phosphorylation in the loop region induces a structural change of active site. CONCLUSION: The phosphorylation of BCL-2 induced structural change in BH3 binding groove.

c-Rel arrests the proliferation of HeLa cells and affects critical regulators of the G1/S-phase transition.

A tetracycline-regulated system was used to characterize the effects of c-Rel on cell proliferation. The expression of c-Rel in HeLa cells led to growth arrest at the G1/S-phase transition, which correlated with its nuclear localization and the induction of endogenous IkappaB alpha expression. These changes were accompanied by a decrease in E2F DNA binding and the accumulation of the hypophosphorylated form of Rb. In vitro kinase assays showed a reduction in Cdk2 kinase activity that correlated with elevated levels of p21WAF1 Cdk inhibitor and p53 tumor suppressor protein. While the steady-state levels of WAF1 transcripts were increased, pulse-chase analysis revealed a sharp increase in p53 protein stability. Importantly, the deletion of the C-terminal transactivation domains of c-Rel abolished these effects. Together, these studies demonstrate that c-Rel can affect cell cycle control and suggest the involvement of the p21WAF1 and p53 cell cycle regulators.

dc-Sheet resistance as sensitive monitoring tool of protein immobilization on thin metal films.

The suitability of high resolution, in situ dc-sheet resistance monitoring (SRM) as a simplified and reliable sensing technique towards detection and tracking of protein immobilization has been explored. Non-specific adsorption of bovine serum albumin (BSA) onto a very thin gold film, acting as the sensing resistor, has been employed as a model system. For comparison, the novel sensing method was combined with surface plasmon resonance (SPR) spectroscopy, using the same flow cell and sensing surface. Two different, well known adsorption states, involving a composite layer of irreversibly and reversibly bound BSA, were clearly resolved by both methods. Clearly structured, pronounced and fully reproducible film resistance modulations have been resolved in the associated SRM data. The transition from reversibly bound BSA to the diluted protein phase is associated with an unusually large decrease in the dc-sheet resistance. The observed resistance modulation magnitude for an adsorbed BSA monolayer corresponds to approximately 1%, and up to 100 mOmega at a 10 Omega sensing resistor. The sheet resistance of irreversibly bound BSA was determined to 0.24 kOmega/cm2, and the associated specific resistivity estimated to 1-2x10(4) Omega cm.

v-Rel prevents apoptosis in transformed lymphoid cells and blocks TNFalpha-induced cell death.

The v-Rel oncoprotein belongs to the Rel/NF-kappaB family of transcription factors. It transforms chicken lymphoid cells in vitro and induces fatal lymphomas in vivo. In this study, we used a tetracycline-regulated system to characterize the role of v-Rel in cell transformation. We show that the continued expression of v-Rel is necessary to maintain the viability of transformed lymphoid cells and enables primary spleen cells to escape apoptosis in vitro culture. In agreement with a possible role for v-Rel in the inhibition of programmed cell death, its inducible expression in HeLa cells prevented TNFalpha-induced apoptosis. While the repression of v-Rel was accompanied by the rapid degradation of IkappaBalpha, changes in the steady-state levels of the apoptosis inhibitors Bcl-2 and Bcl-X(L) were only observed following the onset of cell death in transformed lymphoid cells. This suggests that the anti-apoptotic activity of v-Rel may affect other apoptosis inhibitors or other factors in the death pathway. Together, these findings demonstrate that v-Rel blocks apoptosis and suggest that this activity may be an important component of its transforming function.

N-terminal determinants of I kappa B alpha necessary for the cytoplasmic regulation of c-Rel.

I kappa B alpha is a dual regulator of Rel/NF-kappa B transcription factors. I kappa B alpha retains inactive NF-kappa B dimers in the cytoplasm, and inhibits their DNA-binding and transcriptional activities in the nucleus. Our previous studies identified discrete functional domains in I kappa B alpha responsible for the cytoplasmic and nuclear regulation of c-Rel. Determinants necessary for regulating c-Rel in the nucleus mapped to the central ankyrin domain of I kappa B alpha and a few negatively-charged amino acids that follow in the C-terminal PEST region. In contrast, sequences involved in the cytoplasmic regulation of c-Rel reside in the N-terminal and central ankyrin domains of I kappa B alpha. Here, we present a refined mapping of the N-terminal determinants of I kappa B alpha necessary for the cytoplasmic regulation of c-Rel homodimers. We demonstrate that amino acids 48 - 58 in p40/I kappa B alpha are essential to block the nuclear localization of c-Rel dimers. These data define a region of I kappa B alpha that may be required for optimal masking of the c-Rel NLS, or for the nuclear export of c-Rel/I kappa B alpha complexes. These findings highlight a novel function for the N-terminus of I kappa B alpha in the control of the subcellular localization of Rel/NF-kappa B dimers. Given the implication of deregulated NF-kappa B activity in hematopoietic and solid tumors, our findings predict that certain alterations in this domain of I kappa B alpha may have severe biological repercussions.

Rel blocks both anti-Fas- and TNF alpha-induced apoptosis and an intact Rel transactivation domain is essential for this effect.

The v-Rel oncoprotein must be continuously expressed to prevent the apoptosis of transformed lymphoid cells, and also inhibits TNF alpha-induced cell death. A tetracycline-regulated cell system was used to characterize the functions necessary for the anti-apoptotic activity of Rel proteins. v-Rel mutants defective for DNA binding or transactivation showed no protective effect. Similarly, whereas the transcription-competent c-Rel and RelA proteins inhibited TNF alpha-induced cytolysis, the transactivation-negative p50/NF-kappa B1 did not. Importantly, this study is the first to show that c-Rel can also confer significant protection from Fas-mediated cell death. Since the TNFR1- and Fas-signaling pathways involve some intermediates that are common and others that are unique to each pathway, these findings indicate that c-Rel may regulate the expression of genes that function to antagonize either or both death-signaling pathways.

Knowledge-based and data-driven models in arrhythmia fuzzy classification.

OBJECTIVES: Fuzzy rules automatically derived from a set of training examples quite often produce better classification results than fuzzy rules translated from medical knowledge. This study aims to investigate the difference in domain representation between a knowledge-based and a data-driven fuzzy system applied to an electrocardiography classification problem. METHODS: For a three-class electrocardiographic arrhythmia classification task a set of fifteen fuzzy rules is derived from medical expertise on the basis of twelve electrocardiographic measures. A second set of fuzzy rules is automatically constructed on thirty-nine MIT-BIH database's records. The performances of the two classifiers on thirteen different records are comparable and up to a certain extent complementary. The two fuzzy models are then analyzed, by using the concept of information gain to estimate the impact of each ECG measure on each fuzzy decision process. RESULTS: Both systems rely on the beat prematurity degree and the QRS complex width and neglect the P wave existence and the ST segment features. The PR interval is not well characterized across the fuzzy medical rules while it plays an important role in the data-driven fuzzy system. The T wave area shows a higher information gain in the knowledge based decision process, and is not very much exploited by the data-driven system. CONCLUSIONS: The main difference between a human designed and a data driven ECG arrhythmia classifier is found about the PR interval and the T wave.

Reduction of false arterial blood pressure alarms using signal quality assessment and relationships between the electrocardiogram and arterial blood pressure.

The paper presents an algorithm for reducing false alarms related to changes in arterial blood pressure (ABP) in intensive care unit (ICU) monitoring. The algorithm assesses the ABP signal quality, analyses the relationship between the electrocardiogram and ABP using a fuzzy logic approach and post-processes (accepts or rejects) ABP alarms produced by a commercial monitor. The algorithm was developed and evaluated using unrelated sets of data from the MIMIC database. By rejecting 98.2% (159 of 162) of the false ABP alarms produced by the monitor using the test set of data, the algorithm was able to reduce the false ABP alarm rate from 26.8% to 0.5% of ABP alarms, while accepting 99.8% (441 of 442) of true ABP alarms. The results show that the algorithm is effective and practical, and its use in future patient monitoring systems is feasible.