Miracle-dz/UniFAR-FTUs huggingface dataset:
Normal Heart Rate Variability in Colchicine-Resistant Familial Mediterranean Fever Patients.

BACKGROUND The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF. OBJECTIVES To evaluate ANS function in colchicine non-responders by using the HRV tool. METHODS The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls. RESULTS No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters. CONCLUSIONS Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults.
Vibration analysis of a suspension system subject to high level of measurement noise

Using only vertical acceleration measurements for the sprung and unsprung masses of a suspension system of a commercial city bus, the goal of the paper is to develop an analysis method to find the vibration modes of the mechanical system from data measured during real life operation. The identified vibration modes can be used to (in)validate first principle physical models of the system, while the identified ARMA models can be used to develop uncertainty models. The challenge in the problem is that the measurements are subject to very high level of noise due to maneuvering of the vehicle, nonlinear effects of the suspension system, vibration of the engine and the gear system, and sensor noise. Nonparametric and parametric modeling methods are applied to evaluate the quality of the measurements and find the invariant properties of the suspension system. It is shown based on multiple experiments that independently of the actual road properties and operating conditions, eigen-frequencies of some vibration modes can be determined with relatively small uncertainty, while the corresponding damping factors have varying amount of uncertainty. Comparing the results with the modes of a full car vehicle model developed based on physical considerations, it can be concluded that an identification algorithm for obtaining the parameters of the physical model must be complemented with a suitable uncertainty modeling and classification.
Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus

Uterine glands and their secretions are indispensable for endometrial function and fertility; however, the mechanisms regulating their development and function are not well understood. Forkhead transcription factor box A2 (FOXA2) is uniquely expressed in the glandular epithelial (GE) cells of the uterus, and conditional deletion of Foxa2 after birth impedes uterine gland development. An integrative approach was used here to define the FOXA2 cistrome in the murine uterus. Genome‐wide mapping of FOXA2 binding sites was combined with transcriptomic analyses of isolated GE and Foxa2‐deleted uteri. ChIP‐Seq analyses found the number of FOXA2 target genes was substantially greater in the adult (8893) than neonatal uterus (1101). In the neonatal uterus, FOXA2‐bound and GE‐expressed genes (469) were enriched for developmentally related processes, including cell cycle, cell junction, focal adhesion, and WNT signaling. In the adult uterus, FOXA2‐bound and GE‐expressed genes (3730) were enriched for functional processes, including metabolic pathways, focal adhesion, bacterial invasion of epithelial cells, and WNT signaling. Analysis of the uterine FOXA2 cistrome provides novel insights into mechanisms governing endometrial gland development and function, which are important to understand fundamental aspects of uterine differentiation, regeneration and disease. —Filant, J., Lydon, J. P., Spencer, T. E. Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus. FASEB J. 28, 230–243 (2014). www.fasebj. org
Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

Background Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. Methods Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. Results One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%–75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). Conclusion Patients treated with RCI had less PPPM non-medication MRU and costs than those treated with IVIg and/or rituximab, particularly in the hospital setting where significant costs are incurred.
Taxing Interest on Deposits: Theoretical and Empirical Analysis for the Case of Lebanon

In most countries, taxes on interest income are subsumed under the general income tax structure. In Lebanon, there is a departure from such a policy, and these taxes are not imposed as part of taxable income but are levied at source on interest from deposits at commercial banks. As a result, this necessitates the derivation of a theoretical model on the subject of this tax that must be applicable to Lebanon. This is the first intent of this paper. As such, the paper develops a model that attempts to maximize the tax revenue from a given tax rate and to minimize the deadweight loss from this tax. From this theory, the relevant parameters that affect the optimal tax rate are found to be the interest rate elasticities of deposit supply and demand. Assuming, as the case for Lebanon indicates, that the interest elasticity of demand for deposits is infinite, and conditioning on other exogenous variables, the own and cross interest elasticities of deposit supply are estimated by advanced econometric techniques. The results show that the optimal tax rates differ markedly for the two denominations of deposits, the one in Lebanese pounds and the one in foreign currency. The optimal tax rate is higher for the latter, and both rates are much higher than the actual rate, or even the proposed rate. The paper concludes that, although tax authorities in Lebanon can theoretically raise substantially the tax rate in order to increase tax revenues, other economic and political considerations limit to a large degree the liberty of implementing such a raise.
Activation of extracellular signal‐regulated kinases ERK1 and ERK2 induces Bcl‐xL up‐regulation via inhibition of caspase activities in erythropoietin signaling

Erythropoietin (EPO) can rescue erythroid cells from apoptosis during erythroid development, leading to red cell production. However, the detailed mechanism of how EPO protects erythroid cells from apoptosis is still open to question. To address this problem, we used a human EPO‐dependent leukemia cell line UT‐7/EPO and normal erythroid progenitor cells. After deprivation of EPO, UT‐7/EPO cells underwent apoptosis, accompanied by down‐regulation of the Bcl‐xL protein. In addition, the cleaved products of caspase‐3, p11 and p21, and a few cleaved forms of inhibitor of caspase‐activated DNase (ICAD) were detected in these cells. When the cells were pre‐treated with the pancaspase inhibitor Z‐VAD‐FMK, the ratio of apoptotic cells was significantly reduced, suggesting that EPO protects the UT‐7/EPO cells from apoptosis via inhibition of caspase activities. When an MEK 1/2 inhibitor U0126 inhibited activities of extracellular signal‐regulated kinases (ERKs), the expression of Bcl‐xL protein was down‐regulated and subsequently apoptosis was induced. Interestingly, Z‐VAD‐FMK blocked U0126‐induced down‐regulation of Bcl‐xL protein and apoptosis, strongly suggesting that Bcl‐xL expression is regulated by caspases which lies downstream of ERK activation pathway in EPO signaling. Importantly, these findings were also observed in normal erythroid progenitor cells. In conclusion, the activation of ERKs by EPO up‐regulates Bcl‐xL expression via inhibition of caspase activities, resulting in the protection of erythroid cells from apoptosis. © 2003 Wiley‐Liss, Inc.
Using the Medipix2 detector for photon counting computed tomography

The Medipix2 detector is a photon counting hybrid pixel detector. It consists of 256 by 256 pixels (55/spl times/55 /spl mu/m/sup 2/ each) with a semiconductor sensor layer. Two thresholds enable X-ray imaging with an energy window. Integration of this detector into our setup requires very precise alignment of all devices: Precision of up to 0.05/spl deg/ and 10 /spl mu/m was realised with special objects. For the verification of the system resolution we constructed phantoms with high contrast at high spatial frequency. The resolution limit of our setup is about 50 /spl mu/m which is dominated by the relatively large X-ray spot size. Further on we investigated the impact of flatfield correction on ring artifacts and additionally applied a special filtering algorithm for suppression of those. Computed tomography acquisition series with different organic objects have been carried out to prove the system performance for realistic imaging tasks: Using a peanut as well as a newborn mouse produced high quality volume data sets. In addition, we used the quad version of the Medipix2 detector (2/spl times/2 ASICS) for CT of larger objects with diameters up to 26 mm. With Monte-Carlo simulations we investigated the interaction of energy weighting with the filtered back projection algorithm if energy resolved data is available: Applying the energy weighting technique before filtering and back projection or afterwards; or with intermixed order for different energy intervals and different kernels. We propose weighting before filtering and recommend smoothing kernels for lower photon energies and high resolution kernels for energy intervals with higher statistics.
Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1‐FPR2/ALX anti‐inflammatory system

Unregulated inflammation underlies many diseases, including sepsis. Much interest lies in targeting anti‐inflammatory mechanisms to develop new treatments. One such target is the anti‐inflammatory protein annexin A1 (AnxA1) and its receptor, FPR2/ALX. Using intravital videomicroscopy, we investigated the role of AnxA1 and FPR2/ALX in a murine model of endotoxin‐induced cerebral inflammation [intraperitoneal injection of lipopolysaccharide (LPS)]. An inflammatory response was confirmed by elevations in proinflammatory serum cytokines, increased cerebrovascular permeability, elevation in brain myeloperoxidase, and increased leukocyte rolling and adhesion in cerebral venules of wild‐type (WT) mice, which were further exacerbated in AnxA1‐null mice. mRNA expression of TLR2, TLR4, MyD‐88, and Ly96 was also assessed. The AnxA1‐mimetic peptide, AnxA1Ac2‐26 (100 μg/mouse, ~33 μmol) mitigated LPS‐induced leukocyte adhesion in WT and AnxA1‐null animals without affecting leukocyte rolling, in comparison to saline control. AnxA1Ac2‐26 effects were attenuated by Boc2 (pan‐FPR antagonist, 10 μg/mouse, ~12 nmol), and by minocycline (2.25 mg/mouse, ~6.3 nmol). The nonselective Fpr agonists, fMLP (6 μg/mouse, ~17 nmol) and AnxA1Ac2‐26, and the Fpr2‐selective agonist ATLa (5 μg/mouse, ~11 nmol) were without effect in Fpr2/3–/– mice. In summary, our novel results demonstrate that the AnxA1/FPR2 system has an important role in effecting the resolution of cerebral inflammation in sepsis and may, therefore, provide a novel therapeutic target. —Gavins, F. N. E. , Hughes, E. L. , Buss, N. A. P. S. , Holloway, P. M. , Getting, S. J., Buckingham, J. C. Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1‐FPR2/ALX anti‐inflammatory system. FASEB J. 26, 4977–4989 (2012). www.fasebj. org
Novel GluN2B selective NMDA receptor antagonists: relative configuration of 7-methoxy-2-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ols

Introduction of the flexible aminoalcohol substructure of ifenprodil into a more rigid ring system resulted in 2-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ols, (3) and (4), showing GluN2B affinity in the low nanomolar range. The chiral pool synthesis starting with (R)-alanine led to two diastereomers. The relative configuration of the benzazepines (3) and (4), that crystallized as racemates, was determined to be (S*,R*)-3 and (R*,R*)-4.
Structural Transformation, Services Deepening, and the Transmission of Monetary Policy

Advanced economies are undergoing a structural transformation from manufacturing to services. We document that structural change comes with a process of services deepening: over time, both services and manufacturing become more intensive in service inputs. We argue that structural transformation and services deepening affect the transmission of monetary policy by increasing the relative importance of services, which have stickier prices than manufacturing. We study the implications of the U.S. sectoral reallocation with a New Keynesian model with two sectors connected by an input-output matrix, which varies endogenously over time. The rise of services dampens the responses of aggregate and sectoral inflation rates to a monetary policy shock. The changes in the responses of sectoral inflation rates are entirely driven by services deepening.
TEL‐AML1 fusion in acute lymphoblastic leukaemia of adults

A number of fusion genes have been identified by study of acquired chromosomal translocations. Their detailed characterization has provided insights into mechanisms of leukaemogenesis and has enabled the development of molecular methods to assist in the diagnosis and monitoring of residual disease after treatment. The TEL‐AML1 fusion gene is associated with a cryptic t(12;21)(p12;q22) translocation, and is the commonest known genetic abnormality in childhood B‐cell precursor acute lymphoblastic leukaemia (ALL), occurring in about 25% of cases. We have used RT‐PCR, followed by Southern blotting and direct sequencing, to establish the incidence of TEL‐AML1 rearrangement in 131 adults with acute leukaemia (101 with ALL and 30 with chronic myeloid leukaemia in blastic crisis). Three patients were positive for TEL‐AML1 transcripts. All three had common‐ALL. All other patients were negative for TEL‐AML1. We conclude that the TEL‐AML1 fusion gene is found in adult ALL, though less commonly than in children.
Statistics of a passive scalar advected by a large-scale two-dimensional velocity field: Analytic solution.

Steady statistics of a passive scalar advected by a random two-dimensional flow of an incompressible fluid is described in the range of scales between the correlation length of the flow and the diffusion scale. That corresponds to the so-called Batchelor regime where the velocity is replaced by its large-scale gradient. The probability distribution of the scalar in the locally comoving reference frame is expressed via the probability distribution of the line stretching rate. The description of line stretching can be reduced to a classical problem of the product of many random matrices with a unit determinant. We have found the change of variables that allows one to map the matrix problem onto a scalar one and to thereby prove the central limit theorem for the stretching rate statistics. The proof is valid for any finite correlation time of the velocity field. Whatever the statistics of the velocity field, the statistics of the passive scalar (averaged over time locally in space) is shown to approach gaussianity with increase in the Peclet number $Pe$ (the pumping-to-diffusion scale ratio). The first $n<\ln Pe$ simultaneous correlation functions are expressed via the flux of the square of the scalar and only one factor depending on the velocity field: the mean stretching rate, which can be calculated analytically in limiting cases. Non-Gaussian tails of the probability distributions at finite $Pe$ are found to be exponential.
Genetic and physical analyses of the growth rate-dependent regulation of Escherichia coli zwf expression

Growth rate-dependent regulation of the level of Escherichia coli glucose 6-phosphate dehydrogenase, encoded by zwf, and 6-phosphogluconate dehydrogenase, encoded by gnd, is similar during steady-state growth and after nutritional upshifts. To determine whether the mechanism regulating zwf expression is like that of gnd, which involves a site of posttranscriptional control located within the structural gene, we prepared and analyzed a set of zwf-lacZ protein fusions in which the fusion joints are distributed across the glucose 6-phosphate dehydrogenase coding sequence. Expression of beta-galactosidase from the protein fusions was as growth rate dependent as that of glucose 6-phosphate dehydrogenase itself, indicating that regulation does not involve an internal regulatory region. The level of beta-galactosidase in zwf-lac operon fusion strains and the level of zwf mRNA from a wild-type strain increased with increasing growth rate, which suggests that growth rate control is exerted on the mRNA level. The half-life of the zwf mRNA mass was 3.0 min during growth on glucose and 3.4 min during growth on acetate. Thus, zwf transcription appears to be the target for growth rate control of the glucose 6-phosphate dehydrogenase level.
Electrodermal responses and memory recall in migraineurs and headache‐free controls

Chronic pain patients show increased peripheral activity when exposed to stimuli relevant to their pain problem. It has been suggested that in migraine there is a highly specific conditioning or sensitization to pain stimuli. The aims of this study were to analyse whether migraineurs (1) are sensitive not only to pain‐related but also to other negative emotional words; and (2) show a memory bias for pain words, when compared to headache‐free controls.
Gan comb-drive actuators on Si substrate

Micro-electro-mechanical comb-drive actuators made of GaN crystal are studied for an integrated a tunable GaN optical device. The GaN crystal was grown on a Si substrate by metal-organic chemical vapor deposition (MOCVD) with a low-temperature buffer layer. Selectively etching the Si substrate by XeF2 gas, the GaN thin crystal layers are self-supported in air. Due to the residual stress by the crystal growth, the freestanding GaN layer of actuator suffers from the considerable deformation depending on the growth conditions. To compensate the convex deformation, the crystallization tension of thin HfO2 film deposited on the GaN layer is used. The displacement is 1.3 µm at 70V. The fabricated GaN actuator can be useful for the monolithic integration for tunable GaN light sources.
Association of the +874 T/A interferon gamma polymorphism with infections in sickle cell disease

Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. Several mechanisms are supposed to contribute to this susceptibility. The exact reasons for the susceptibility of sickle cell patients to infection are not clear and are still a matter of debate. Interferon gamma (IFNγ) is a key cytokine involved mainly in the defence against intracellular pathogens. We investigated a possible association of an IFNγ +874 T/A polymorphism and infectious complications in sickle cell patients. Seventy‐two sickle cell patients were typed for +874 T/A IFNγ polymorphism. Genotype frequencies were different between cases and controls. Indeed, the T allele frequency was significantly higher in patients with infections than in patients without infections (P = 0.014). Our results suggest that the +874 T/A IFNγ polymorphism is associated with infectious complications in sickle cell patients. T allele could be involved in infections in sickle cell patients.
Nutrition-based health in animal production

Events such as BSE, foot and mouth disease and avian influenza illustrate the importance of animal health on a global basis. The only practical solution to deal with such problems has usually been mass culling of millions of animals at great effort and expense. Serious consideration needs to be given to nutrition as a practical solution for health maintenance and disease avoidance of animals raised for food. Health or disease derives from a triad of interacting factors; diet–disease agent, diet–host and disease agent–host. Various nutrients and other bioactive feed ingredients, nutricines, directly influence health by inhibiting growth of pathogens or by modulating pathogen virulence. It is possible to transform plant-based feed ingredients to produce vaccines against important diseases and these could be fed directly to animals. Nutrients and nutricines contribute to three major factors important in the diet–host interaction; maintenance of gastrointestinal integrity, support of the immune system and the modulation of oxidative stress. Nutrition-based health is the next challenge in modern animal production and will be important to maintain economic viability and also to satisfy consumer demands in terms of food quality, safety and price. This must be accomplished largely through nutritional strategies making optimum use of both nutrients and nutricines.