Miracle-dz/UniFAR-FTUs huggingface dataset:
A Randomized Multicenter Study of Optimal Circadian Time of Vinorelbine Combined with Chronomodulated 5‐Fluorouracil in Pretreated Metastatic Breast Cancer Patients: EORTC Trial 05971

Studies in animals synchronized with an alternation of 12 h of light and 12 h of darkness have showed that hematological and systemic toxicities could be reduced if vinorelbine were administered 19 or 23 hours after light onset (HALO), corresponding to 17:00 and 21:00 h in diurnally active humans. This trial aimed to define the least toxic time of vinorelbine administration in metastatic breast cancer patients. Initially, the study treatment consisted of three courses of vinorelbine of 30 mg/m2/d on D1 and D6 and chronomodulated 5‐fluorouracil of 850 mg/m2 from D2 to D5 every 21 days. Ninety metastatic breast cancer patients were randomized to receive vinorelbine at one of the eight possible dosing times. Further to the recommendations of the Independent Data Monitoring Committee, the vinorelbine dose was reduced to 25 mg/m2/d midway through the study. The primary objective of the study was detection of the least toxic time based on the incidence of grade 3–4 (G3–4) neutropenia. To show a significant result, the 90% confidence interval width of the least toxic time had to be<6 h. The least toxic time detection based on the incidence of other toxicities was also analyzed. The time of least drug toxic was estimated using a logistic regression model assuming that the logit transformation of the toxicity rate follows a sinusoidal distribution over 24 h. The bootstrap technique was used to obtain the 90% confidence interval. The least toxic time of G3–4 neutropenia was observed at 21:00 h with a non‐significant 90% CI. Secondary endpoint analyses indicated the least toxic time could differ when based on other toxicity parameters (e.g., a significant least toxic time of 17:00 h was observed for G3–4 leucopenia), in agreement with animal data. The least toxic time of 10:30 h was estimated for any G3–4 gastrointestinal toxicity. This results of this study do not allow us to recommend an optimal time for vinorelbine administration. It has highlighted, however, the inherent methodological difficulties in the conduct of such a trial in the human setting. It indicates that future optimal time‐finding trials should have tolerability and/or activity as the primary endpoint in place of a particular toxicity. The randomized optimal time‐finding design may be used to identify the best time of chemotherapy administration. (Author correspondence: bcoudert@dijon.fnclcc.fr)
Age and rest–activity rhythm as predictors of survival in patients with newly diagnosed lung cancer

ABSTRACT Disruption of the rest–activity rhythm in patients with lung cancer can accelerate cancer progression and affect survival. Rest–activity rhythm changes with age. Therefore, we investigated the effects of rest–activity rhythm and age on patients’ survival. A total of 84 patients with lung cancer were recruited, then separated into two groups; younger patients aged under 65 years or elderly patients aged 65 and over. The dichotomy index (I < O) was used to estimate the rest–activity rhythm measured through the actigraphy motion detector. Cox proportional hazards models were adopted to investigate the effects of different variables on the patients’ survival. After adjusting for confounding, the risk of earlier mortality in the younger patients with disrupted I < O were 2.52 (95%CI = 1.09–5.82) times higher than that in the younger patients with robust I < O (p = 0.03), the risk of earlier mortality in the elderly patients with disrupted I < O was 4.08 (95%CI = 1.91–8.68) times higher than that in the elderly patients with robust I < O (p < 0.001). Therefore, age and I < O influence the survival period of patients with lung cancer. Moreover, disrupted I < O has a substantial influence on elderly patients. In conclusion, aging and disrupted rest–activity rhythm negatively and jointly influenced the survival period of the patients with lung cancer and significantly increased their death risk.
Self‐reported moderate‐to‐vigorous leisure time physical activity predicts less pain and disability over 12 months in chronic and persistent low back pain

Physical deconditioning in combination with societal and emotional factors has been hypothesized to compromise complete recovery from low back pain (LBP). However, there is a lack of longitudinal studies designed to specifically investigate physical activity as an independent prognostic factor. We conducted a prognostic study to investigate whether levels of leisure time physical activity are independently associated with clinical outcomes in people seeking care for chronic and persistent LBP.
A Pathway to National Guidelines for Laboratory Diagnostics of Chronic Kidney Disease – Examples from Diverse European Countries

The principal benefit of guidelines is to improve the quality of care received by patients. In the 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (KDIGO) was released and it is designed to provide information and assist decision making. This review gives a brief overview of a various national CKD guidelines that rely on the newly released KDIGO guidelines. All of the included countries (France, Turkey, Norway and Croatia) are non-English speaking countries and they differ in population and socio economic aspects. Examples shown in this review may provide valuable experience for countries that are in process of creating their national CKD guidelines.
Hydrolysis of Phosphatidylinositol 4,5-Bisphosphate Mediates Calcium-induced Inactivation of TRPV6 Channels*

TRPV6 is a member of the transient receptor potential superfamily of ion channels that facilitates Ca2+ absorption in the intestines. These channels display high selectivity for Ca2+, but in the absence of divalent cations they also conduct monovalent ions. TRPV6 channels have been shown to be inactivated by increased cytoplasmic Ca2+ concentrations. Here we studied the mechanism of this Ca2+-induced inactivation. Monovalent currents through TRPV6 substantially decreased after a 40-s application of Ca2+, but not Ba2+. We also show that Ca2+, but not Ba2+, influx via TRPV6 induces depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) and the formation of inositol 1,4,5-trisphosphate. Dialysis of DiC8 PI(4,5)P2 through the patch pipette inhibited Ca2+-dependent inactivation of TRPV6 currents in whole-cell patch clamp experiments. PI(4,5)P2 also activated TRPV6 currents in excised patches. PI(4)P, the precursor of PI(4,5)P2, neither activated TRPV6 in excised patches nor had any effect on Ca2+-induced inactivation in whole-cell experiments. Conversion of PI(4,5)P2 to PI(4)P by a rapamycin-inducible PI(4,5)P2 5-phosphatase inhibited TRPV6 currents in whole-cell experiments. Inhibiting phosphatidylinositol 4 kinases with wortmannin decreased TRPV6 currents and Ca2+ entry into TRPV6-expressing cells. We propose that Ca2+ influx through TRPV6 activates phospholipase C and the resulting depletion of PI(4,5)P2 contributes to the inactivation of TRPV6.
Development of hand-eye system with 3-D vision and microgripper and its application to assembling flexible wires

A hand-eye system with 3-D vision system and a microgripper has been developed for handling, forming and inserting flexible wires in electronic assembles. The hand-eye system performs its task based on visual sensor and force sensor data. The vision system uses a camera, a laser-multiplanar light projector, and a videorate image processor to measure the 3-D geometry of flexible wires within one robot cycle. The measurement accuracy is better than 1 mm perpendicular to the plane for a depth of 500 mm. The microgripper has three-axis sensors capable of detecting three kinds of forces; grasping, pulling, and pushing. The dynamic range of the grasping force is 0.5 to 60 gf. This system has been used for wire assembling in magnetic-disk slider manufacture. Using recovery function, the success ratios for measurement, grasping and upper insertion were 100%. The design concepts, the 3-D measurement, the hand-eye system, and the wire-assembling application are discussed. <<ETX>>
Finite-dimensional approximation of convex regularization via hexagonal pixel grids

This work extends the existing convergence analysis for discrete approximations of minimizers of convex regularization functionals. In particular, some solution concepts are generalized, namely the standard minimum norm solutions for squared-norm regularizers and the -minimizing solutions for general convex regularizers, respectively. A central part of the manuscript addresses finite-dimensional approximations of solutions of ill-posed operator equations with basis functions defined on hexagonal grids, which require the novel solution concept.
AOD/AOA/TOA-based 3D positioning in NLOS multipath environments

Wireless localization has attracted increasing attention from both researchers and engineers. Most of the state-of-the-art localization techniques are designed based on line-of-sight (LOS) radio propagation. The present paper focuses on indoor scenarios which are multipath and rich scattering environments considering non-line-of-sight (NLOS) propagations. Based on the measured angle-of-departure (AOD), angle-of-arrival (AOA), and time-of-arrival (TOA), we propose a three dimensional (3D) least squares (LS) positioning technique assuming a single-bounce reflection in every NLOS propagation path. Furthermore, we derive the Cramer-Rao lower bound (CRLB) for the root mean-square error (RMSE) of the mobile station (MS) position estimate. The system performance is assessed not only based on Monte-Carlo simulations and the analytical CRLB, but also based on real world measurements. It is shown that the proposed technique can accurately estimate the MS position with a root square error of approximately 21 cm in a real laboratory room.
Significant vertical water transport by mountain‐induced circulations on Mars

Using a 3‐D, non‐hydrostatic mesoscale Mars atmospheric model with detailed aerosol/cloud microphysics, we show that the formation of discrete afternoon clouds over the Olympus Mons volcano is due to the symbiosis of upslope thermal flow and a lee mountain wave circulation, and that these clouds exhibit complex particle distributions. Furthermore, we illustrate that this and other mountain‐induced circulations transport large quantities of dust, water vapor, and water ice aerosol from lower altitudes into the free atmosphere general circulation. Therefore, these circulations are an important part of Mars' net Hadley circulation and climatic forcing.
A potential peptide pathway from viruses to oral lichen planus

Oral lichen planus is an idiopathic inflammatory disease of oral mucous membranes, characterized by an autoimmune epidermis attack by T cells. It remains unknown, however, how such aggressive T cells are activated in vivo to cause epidermal damage. This study analyzes the relationship at the peptide level between viruses and oral lichen planus disease. Four potentially immunogenic peptides (SSSSSSS, QEQLEKA, LLLLLLA, and MLSGNAG) are found to be shared between HCV, EBV, HHV‐7, HSV‐1, and CMV and three human proteins (namely pinin, desmoglein‐3, and plectin). The described peptide sharing might be of help in deciphering the still unexplained immunopathogenic pathway that leads to oral lichen planus. J. Med. Virol. 87:1060–1065, 2015. © 2015 Wiley Periodicals, Inc.
Numerical Modeling of Intracavity Spectral Broadening of Raman Fiber Lasers

Raman fiber lasers (RFLs) are efficient light sources at frequencies where no other comparable all-solid-state sources are available. Especially if fiber Bragg gratings (FBGs) with narrow bandwidths are used, the bandwidth of the Stokes light is strongly broadened by Kerr nonlinearities like four-wave mixing (FWM), and self- and cross-phase modulation (SPM, XPM). In this letter, we discuss an exact numerical model to calculate the spectral behaviour of RFLs and show its application to determine the effective reflectivity of the FBGs. The model is based on a combination of the nonlinear Schroedinger equation including dispersion, FWM, SPM, and XPM with a shooting method to solve the power steady-state equations for RFLs. Numerical results are in good agreement with measurements.
Parameter estimation of multi Frequency Hopping signals based on compressive spatial time-frequency joint analysis

In order to estimate the parameters of multi Frequency-Hopping(FH) signals in the condition of non-cooperation and overcome the bottleneck of huge data processing, a parameter estimation method based on compressive spatial time-frequency joint analysis is proposed. First the arbitrary compressive array structure is analyzed, then based on this structure we propose a method to estimate the direction of arrivals (DOAs) with only a small number compressive samplings by exploiting the spatial sparsity of multi FH signlas. Then by exploiting the sparsity in frequency domain, a spectrogram estimation algorithm is proposed by using the same compressive sampling. Simulation results show that this algorithm can effectively estimate multi Frequency-Hopping signals' DOAs and specrtograms with a tiny samplings. This algorithm is lower in computation complexity, and can be very practical in real-time Frequency-Hopping signal processing.
Influence of salinity on the localization and expression of the CFTR chloride channel in the ionocytes of Dicentrarchus labrax during ontogeny

The expression and localization of the cystic fibrosis transmembrane conductance regulator (CFTR) were determined in four osmoregulatory tissues during the ontogeny of the sea‐bass Dicentrarchus labrax acclimated to fresh water and sea water. At hatch in sea water, immunolocalization showed an apical CFTR in the digestive tract and integumental ionocytes. During the ontogeny, although CFTR was consistently detected in the digestive tract, it shifted from the integument to the gills. In fresh water, CFTR was not present in the integument and the gills, suggesting the absence of chloride secretion. In the kidney, the CFTR expression was brief from D4 to D35, prior to the larva–juvenile transition. CFTR was apical in the renal tubules, suggesting a chloride secretion at both salinities, and it was basolateral only in sea water in the collecting ducts, suggesting chloride absorption. In the posterior intestine, CFTR was located differently from D4 depending on salinity. In sea water, the basolateral CFTR may facilitate ionic absorption, perhaps in relation to water uptake. In fresh water, CFTR was apical in the gut, suggesting chloride secretion. Increased osmoregulatory ability was acquired just before metamorphosis, which is followed by the sea‐lagoon migration.
Liver MRI at 3 T using a respiratory-triggered time-efficient 3D T2-weighted technique: impact on artifacts and image quality.

OBJECTIVE The purpose of this retrospective study was to qualitatively and quantitatively compare image quality of a time-efficient 3D T2-weighted sequence-the sampling perfection with application-optimized contrasts using different flip angle evolutions (SPACE) sequence-with a standard 2D T2-weighted turbo spin-echo (TSE) sequence for liver imaging at 3 T. MATERIALS AND METHODS Twenty patients underwent liver MRI at 3 T using T2-weighted breath-hold 2D TSE and respiratory-triggered SPACE sequences. Two radiologists independently assessed image quality for both sequences during separate sessions, followed by a side-by-side comparison. One reader performed a quantitative analysis of the estimated signal-to-noise ratio (SNR) and the relative contrast between the liver and other tissues. RESULTS Image quality scores for the SPACE sequence were significantly better than those for the 2D TSE sequence for motion (p < 0.0001) and pulsation (p < 0.0001) artifact, flow signal suppression (p = 0.0015), sharpness of intrahepatic vessels (p < 0.0001), and sharpness of liver edge (p = 0.0015), with motion and pulsation artifacts being nearly eliminated using the SPACE sequence. However, the scores for B(1) inhomogeneity artifact were significantly worse for the SPACE sequence (p = 0.0117). Overall, both readers preferred SPACE sequence, although this difference was significant for only one reader (p = 0.025, p = 0.275). There was no significant difference between the sequences for estimated liver SNR (p = 0.1564), but the SPACE sequence showed significantly higher relative contrast between the liver and the kidney (p < 0.0001), gallbladder (p = 0.0476), and spleen (p < 0.0001). Relative contrast between the liver and parenchymal lesions was higher with the SPACE sequence than with the TSE sequence, although this difference was not statistically significant (p = 0.125). CONCLUSION For T2-weighted liver imaging at 3 T, the respiratory-triggered SPACE sequence shows better image quality with near elimination of motion and pulsation artifacts and improved tissue contrast than the breath-hold 2D TSE sequence, but suffers from increased B(1) inhomogeneity artifact and longer scanning time.
Canopy Architecture of Natural and Planted Cordgrass Marshes: Selecting Habitat Evaluation Criteria.

In order to set standards for restoration or mitigation "success" of salt marsh habitat designed for an endangered southern California bird, I explored the bird's nesting requirements, compared constructed habitats that lack the bird with natural habitats that support it, and selected habitat assessment criteria that best distinguish suitable and unsuitable nesting habitats. Selected attributes of canopy architecture are recommended for assessing the suitability of intertidal cordgrass (Spartina foliosa) marshes for the endangered Light-footed Clapper Rail (Rallus longirostris levipes) of southern California. Nests are built at °145 cm above Mean Lower Low Water (MLLW = 0 tidal datum), with nest rims at °165-170 cm MLLW; however, extreme high water is 232 cm MLLW during the March-July nesting season, and tidal inundation is a major cause of nest failure. Cordgrass that is >60 cm tall appears necessary for birds to weave a canopy that allows the nest to float upward, but not away, as the tide rises. Cordgrass height distributions and density data describe attributes of canopy architecture that assess Clapper Rail habitat value better than previously used measures (i.e., cover, biomass, mean height, maximum height). Height histograms differ for planted marshes (which do not support Clapper Rails) and natural marshes. The constructed marshes have few plants over 60 cm, while most stems in natural marshes exceed 60 cm. In natural marshes, cordgrass heights increase with freshwater flooding and nitrogen enrichment. Reference data from natural marshes that are used by Clapper Rails indicate that the standard for "suitable habitat" should be a density of at least 100 stems/m2 with at least 90 stems/m2 >60 cm, of which at least 30 stems/m2 are >90 cm in height. High interannual and spatial variability indicates the need for several (e.g., 20) years of data for assessment purposes and a large data base for reference wetlands.
Modulation of Gene Expression by the MHC Class II Transactivator1

The class II transactivator (CIITA) is a master regulator of MHC class II expression. CIITA also modulates the expression of MHC class I genes, suggesting that it may have a more global role in gene expression. To determine whether CIITA regulates genes other than the MHC class II and I family, DNA microarray analysis was used to compare the expression profiles of the CIITA expressing B cell line Raji and its CIITA-negative counterpart RJ2.2. 5. The comparison identified a wide variety of genes whose expression was modulated by CIITA. Real time RT-PCR from Raji, RJ2.2. 5, an RJ2.2. 5 cell line complemented with CIITA, was performed to confirm the results and to further identify CIITA-regulated genes. CIITA-regulated genes were found to have diverse functions, which could impact Ag processing, signaling, and proliferation. Of note was the identification of a set of genes localized to chromosome 1p34-35. The global modulation of genes in a local region suggests that this region may share some regulatory control with the MHC.
Robust static and fixed‐order dynamic output feedback control of discrete‐time parametric uncertain Luré systems: Sequential SDP relaxation approaches

Design methods are proposed for static and fixed‐order dynamic output feedback controllers for discrete‐time Luré systems with sector‐bounded nonlinearities in the presence of parametric uncertainties described by polytopes. The derived design conditions are represented in terms of bilinear matrix inequalities, which are nonconvex. By using convex relaxation methods, controller design equations are derived for systems with multiple states, outputs, and nonlinearities in terms of linear matrix inequalities (LMIs) and iterative LMIs, which are associated with semidefinite programs. The proposed design methods are developed from stability conditions using parameter‐dependent Lyapunov functions, and existing iterative numerical methods are adapted to solve certain classes of nonconvex optimization problems for controller design. Several numerical examples are provided to illustrate and verify the proposed design methods. Copyright © 2016 John Wiley & Sons, Ltd.
Modeling of high power automotive batteries by the use of an automated test system

In order to estimate the field of application for an electrical energy storage, its performance at different operating conditions has to be measured and evaluated. An automated test system has been designed to speed up measurement and to ensure reproducible measurement conditions. This paper focuses on the performance of this test system and on measured data. Based on this data, a battery model of a NiMH cell is parameterized and the obtained results are discussed.
Regulation of the Escherichia coli heat‐shock response

Steady‐state‐ and stress‐induced expression of Escherichia coli heat‐shock genes is regulated at the transcriptional level through controls of concentration and activity of the positive regulator, the heat‐shock promoter‐specific subunit of RNA polymerase, σ;32. Central to these controls are functions of the DnaK, DnaJ, GrpE heat‐shock proteins as negative modulators that mediate degradation as well as repression of activity and, in some conditions, of synthesis of σ32. DnaJ has a key role in modulation since it binds σ32 and, jointly with DnaK and GrpE, represses its activity. Furthermore, DnaJ is capable of binding heat‐damaged proteins, targeting DnaK and GrpE to these substrates, and thereby mediating DnaK‐, DnaJ‐, GrpE‐dependent repair. It is proposed that one important signal transduction pathway that converts stress to a heat‐shock response relies on the sequestering of DnaJ through binding to damaged proteins which derepresses and stabilizes σ32. Damage repair ameliorates the inducing signal and frees DnaJ, DnaK, GrpE to shut off the heat‐shock response.
Homotypic receptor-receptor interactions regulating Eph signaling

The Eph receptor tyrosine kinases and their ephrin ligands direct axon pathfinding and neuronal cell migration, and mediate many other cell-cell communication events. The Ephs and ephrins both localize to the plasma membrane and, upon cell-cell contact, form extensive signaling assemblies at the contact sites. Recent structural, biochemical and cell-biological studies revealed that these assemblies are generated not only via Eph-ephrin interactions, but also via homotypic interactions between neighboring receptor molecules. In addition, Eph-Eph interactions mediate receptor pre-clustering, which ensures fast and efficient activation once ligands come into contact range. Here we summarize the current knowledge about the homotypic Eph-Eph interactions and discuss how they could modulate the initiation of Eph/ephrin signaling.