Miracle-dz/UniFAR-FTUs huggingface dataset:
Association study of the RANK locus in white European rheumatoid arthritis families

Rheumatoid arthritis (RA) linkage has been observed on the 18q chromosome in the white population.1 The 18q locus has also shown evidence of linkage with type I insulin-dependent diabetes mellitus, systemic lupus erythematosus and Grave’s disease.2 A candidate gene on chromosome 18q, the TNFRSF11A ( RANK ) gene, which encodes the receptor activator of nuclear factor kappa B, has been shown to be involved in the osteoclast differentiation playing a pivotal role in bone resorption.3 A single RANK haplotype was reported to be associated with RA in a case–control association study.4 Furthermore, activating mutations in the RANK gene cause bone disorders such as early-onset Paget’s disease,5 expansile skeletal hyperphosphatasia6 and familial expansile osteolysis.7 The aim of this …
Engineering of Functional Manganites Grown by MOCVD for Miniaturized Devices

The hottest and most interesting state‐of‐the‐art research activities carried out in manganite thin films grown by metal‐organic chemical vapor deposition (MOCVD) are reported. The main strategies to tailor their physical properties, such as the impact of the substrate‐induced strain, the defect density, or the influence of stoichiometry in the nanostructured films, are highlighted. Relevant examples of their implementation and integration in miniaturized devices aiming to their future use in information storage, field‐effect sensing, and spintronics applications, are also presented.
Arthritogenic Monoclonal Antibodies from K/BxN Mice

Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patientswe have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10−9 M range, with no indication of cooperative binding between complementing pairs. Pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model. Sequence analysis revealed structural similarities amongst the mAbs, indicating that a particular subset of B cells may evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation likely takes place. These results confirm that GPI itself, rather than a cross-reactive molecule, is the target of pathogenic Igs.
Understanding the aetiology and resolution of chronic otitis media from animal and human studies

ABSTRACT Inflammation of the middle ear, known clinically as chronic otitis media, presents in different forms, such as chronic otitis media with effusion (COME; glue ear) and chronic suppurative otitis media (CSOM). These are highly prevalent diseases, especially in childhood, and lead to significant morbidity worldwide. However, much remains unclear about this disease, including its aetiology, initiation and perpetuation, and the relative roles of mucosal and leukocyte biology, pathogens, and Eustachian tube function. Chronic otitis media is commonly modelled in mice but most existing models only partially mimic human disease and many are syndromic. Nevertheless, these models have provided insights into potential disease mechanisms, and have implicated altered immune signalling, mucociliary function and Eustachian tube function as potential predisposing mechanisms. Clinical studies of chronic otitis media have yet to implicate a particular molecular pathway or mechanism, and current human genetic studies are underpowered. We also do not fully understand how existing interventions, such as tympanic membrane repair, work, nor how chronic otitis media spontaneously resolves. This Clinical Puzzle article describes our current knowledge of chronic otitis media and the existing research models for this condition. It also identifies unanswered questions about its pathogenesis and treatment, with the goal of advancing our understanding of this disease to aid the development of novel therapeutic interventions. Summary: Chronic middle ear inflammation is a common disease. Animal models, and in particular mouse models, have been used to elucidate some potential mechanisms, including dysfunction in immune signalling, mucociliary function or Eustachian tube function.
Resource reclaiming in hard real-time systems with static and dynamic workloads

The paper addresses resource reclaiming in the context of non-preemptive priority list scheduling for hard real-time systems. Such scheduling is inherently susceptible to multiprocessor timing anomalies. The authors present low overhead run-time stabilization methods for a general tasking model that allows phantom tasks as a mechanism to model processor external events. A family of scheduling algorithms is defined, that guarantees run-time stabilization for systems consisting of tasks with hard and soft deadlines. The later, i.e. soft tasks, may arrive dynamically. Stabilization is addressed in the context of dynamic and static task to processor allocation. Previous stabilization methods, focused on a priori stabilization for static workloads with dynamic task to processor allocation, thus cannot support this general scheduling model. By taking advantage of run-time information, the stabilization algorithms use the scan-window approach to prevent instability from occurring. Mechanisms are introduced that explicitly control the run-time behavior of tasks with hard deadlines. As a consequence, processor resources become available that can be used to improve processor utilization and response time of soft tasks. The resulting scan algorithms are intended for real world applications where low run-time overhead and a realistic task model are needed.
Carotenoids need structural colours to shine

The bright colours of feathers are among the most striking displays in nature and are frequently used as sexual signals. Feathers can be coloured by pigments or by ordered tissue, and these mechanisms have traditionally been treated as distinct modes of display. Here we show that some yellow plumage colour is created both by reflection of light from white structural tissue and absorption of light by carotenoids. Thus, structural components of feathers contribute substantially to yellow ‘carotenoid’ displays, but the effect of variation in structural components on variation in colour displays is, to our knowledge, unstudied. The presence of structural colour in some carotenoid-based colour displays will have to be considered in studies of colour signalling.
Head and neck melanoma in the sentinel lymph node era.

OBJECTIVE To determine whether, in the era of sentinel lymph node (SLN) biopsy, head and neck melanoma (HNM) has a poorer outcome than melanomas at other sites (OMS). DESIGN Prospective database, 1994 to 2004. Characteristics and outcomes of patients with HNM vs those with OMS were analyzed by Fisher test, paired t test, and chi(2) test. SETTING Tertiary referral center. PATIENTS A total of 755 patients with melanoma who had undergone SLN biopsy. MAIN OUTCOME MEASURES Differences between patients with HNM and those with OMS. RESULTS A total of 17.4% of patients had HNM vs 82.6% with OMS. There was a male HNM preponderance: 68.7% vs 50.3% for females (P < .01). Patients with HNM were older (mean [SD] age, 57.1 [16.6] years vs 53.3 [16.2] years; P < .01). There were fewer cases of superficial spreading melanoma in patients with HNM (29.0% vs 53.7%; P < .01). There were more diagnoses of lentigo maligna in patients with HNM (26.0% vs 1.9%; P < .01). The mean thickness of the primary lesion was 2.32 (1.9) mm vs 2.31 (2.9) mm; P = . 49. Fewer patients with HNM had Clark level involvement lower than level IV (13.3% vs 24.0%; P < .01). More SLNs were harvested from patients with HNM (3.72 [3.2] vs 2.89 [2.6]; P < .01), but a lower percentage of positive SLNs was found (9.2% vs 16.0%; P < .05). There was no difference in local, regional, or distant recurrence (5.3%, 6.9%, and 5.3%, respectively, in patients with HNM and 3.4%, 5.5%, and 6.7%, respectively, in patients with OMS). The 2- and 5-year survival rates for patients with HNM were 96.2% and 72.6%, respectively, vs 93.6% and 79.0%, respectively, in patients with OMS (P = .40). CONCLUSIONS Most patients with HNM are older males with more SLNs harvested. They do not seem to have poorer outcome than patients with OMS.
Lightweight Multi-DOF Manipulator With Wire-Driven Gravity Compensation Mechanism

Energy consumption is a problem for robotic manipulators, which are popular in manufacturing, assembly, and process handling. Some of the most significant energy consumption comes from the weight of the large moving mass of the manipulator. This paper proposes a new multi-degree-of-freedom (DOF) manipulator with a wire-driven gravity compensation mechanism. The most significant problem of a wire system is the durability of the wire, which is improved in this study by using a multiwinding mechanism. The tension of the wire is reduced in proportion to the number of windings. Timing belts are used to design a multi-DOF manipulator and the lightweight gravity compensation mechanism reduces inertia forces during operation. Static analysis and design issues are presented. A robotic prototype is assembled and the torque-reduction performance is verified experimentally. The proposed mechanism can be applied to industrial manipulators for efficient robotic operation.
Steps Toward 8M Honeycomb Mirrors IV: Some Aspects Of Design And Fabrication

A facility is to be built to make 8m diameter glass honeycomb mirror blanks by casting, in the same way that has been demonstrated with 1.8m blanks. The only major difference is that the larger furnace will he rotated on a turntable so as to preform the deep parabolic surface needed for f/2 mirrors. This paper explores the tolerances in glass homogeneity, thermal control and support of the blank necessary to meet the stringent imaging requirements of telescopes in the best ground based sites. In round numbers, homogenity in expansion coefficient of 10-8/°C and thermal equilibriation to 0.1°C are required. Laboratory measurements show that both can be met by a ventilated honeycomb of borosilicate or similar glass. Adequate resistance to wind pressure and buffeting can be achieved by an axial support that responds to pressure on the three defining points. The total time of about 6 weeks for melting, annealing and cooling of the blanks is set by the time constant of around 8 hours for the glass honeycomb to follow the furnace temperature.
Very tight versus tight control for diabetes in pregnancy.

BACKGROUND Pregnancies complicated by pre-existing insulin dependent diabetes are high risk for a number of poor pregnancy and neonatal outcomes. OBJECTIVES The objective of this review was to assess the effects of very tight glycaemic control in established insulin dependence. SEARCH STRATEGY The Cochrane Pregnancy and Childbirth Group trials register was searched. SELECTION CRITERIA Randomised trials comparing very tight with tight control of diabetes in pregnancy. DATA COLLECTION AND ANALYSIS One reviewer assessed trial quality and extracted data. MAIN RESULTS Two trials involving 182 women were involved. The two trials were difficult to compare. Maternal hypoglycaemia was more common among women whose diabetic control was very tight compared to tight control (odds ratio 25.96, 95% confidence interval 4.91 to 137.26) based on one trial. There was no difference detected in perinatal outcome between the groups. REVIEWER'S CONCLUSIONS There appears to be no clear evidence of benefit from very tight glycaemic control for pregnant diabetic women. Since very strict control may have a substantial impact on lifestyle, this suggests caution in advising such a degree of control.
Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower.

CONTEXT Three fourths of US men older than 50 years have been screened with prostate-specific antigen (PSA) for prostate cancer. OBJECTIVE To estimate the receiver operating characteristic (ROC) curve for PSA. DESIGN, SETTING, AND PARTICIPANTS Calculation of PSA ROC curves in the placebo group of the Prostate Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to 2003 at 221 US centers. Participants were 18 882 healthy men aged 55 years or older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL and normal digital rectal examination results, followed up for 7 years with annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0 ng/mL or rectal examination result was abnormal, a prostate biopsy was recommended. After 7 years of study participation, an end-of-study prostate biopsy was recommended in all cancer-free men. MAIN OUTCOME MEASURES Operating characteristics of PSA for prostate cancer detection, including sensitivity, specificity, and ROC curve. RESULTS Of 8575 men in the placebo group with at least 1 PSA measurement and digital rectal examination in the same year, 5587 (65.2%) had had at least 1 biopsy; of these, 1225 (21.9%) were diagnosed with prostate cancer. Of 1213 cancers with Gleason grade recorded, 250 (20.6%) were Gleason grade 7 or greater and 57 (4.7%) were Gleason grade 8 or greater. The areas under the ROC curve (AUC) for PSA to discriminate any prostate cancer vs no cancer, Gleason grade 7 or greater cancer vs no or lower-grade cancer, and Gleason grade 8 or greater cancer vs no or lower-grade cancer were 0.678 (95% confidence interval [CI], 0.666-0.689), 0.782 (95% CI, 0.748-0.816), and 0.827 (95% CI, 0.761-0.893), respectively (all P values <.001 for AUC vs 50%). For detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of 38.9%, 72.5%, 86.7%, and 93.8%, respectively. Age-stratified analyses showed slightly better performance of PSA in men younger than 70 years vs those 70 years or older with AUC values of 0.699 (SD, 0.013) vs 0.663 (SD, 0.013) (P = .03). CONCLUSION There is no cutpoint of PSA with simultaneous high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather a continuum of prostate cancer risk at all values of PSA.
Inverting the Point Process Model for Fast Phonetic Keyword Search

Normally, we represent speech as a long sequence of frames and model the keyword with a relatively small set of parameters, commonly with a hidden Markov model (HMM). However, since the input speech is much longer than the keyword, suppose instead that we represent the speech as a relatively sparse set of impulses (roughly one per phoneme) and model the keyword as a filter-bank where each filter’s impulse response relates to the likelihood of a phone at a given position within a word. Evaluating keyword detections can then be seen as a convolution of an impulse train with an array of filters. This view enables huge speedups; runtime no longer depends on the frame rate and is instead linear in the number of events (impulses). We apply this intuition to redesign the runtime engine behind the point process model for keyword spotting. We demonstrate impressive real-time speedups (500,000x faster than real-time) with minimal loss in search accuracy.
In Vivo Efficacy in Airway Disease Models of N-(3,5-Dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic Acid Amide (AWD 12-281), a Selective Phosphodiesterase 4 Inhibitor for Inhaled Administration

N-(3,5-Dichloro-pyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281) is a highly potent and selective phosphodiesterase 4 (PDE4) inhibitor that was designed to have a metabolic profile that was optimized for topical administration. The aim of the current study was to explore the pharmacological profile of intratracheally administered AWD 12-281 in different models of asthma and chronic obstructive pulmonary disease (COPD) in comparison with steroids. To assess the anti-inflammatory potential of AWD 12-281, the antigen-induced cell infiltration in bronchoalveolar lavage fluid (BALF) of Brown Norway rats was determined. AWD 12-281 (ID50 of 7 μg/kg i.t.) as well as beclomethasone (0.1 μg/kg i.t.) suppresses late-phase eosinophilia when administered intrapulmonary. Furthermore, AWD 12-281 has also strong anti-inflammatory properties when tested in lipopolysaccharide-induced acute lung neutrophilia in Lewis rats (ID50 of 0.02 μg/kg i.t.), ferrets (ID50 of 10 μg/kg i.t.), and domestic pigs (2–4 mg/pig i.t. or 1 mg/kg i.v.). In pigs, AWD 12-281 was as effective as beclomethasone (0.4 mg/pig i.t.) and dexamethasone (0.28 mg/kg i.v.), although at 3 to 10 times the dosage. The bronchodilatory activity of AWD 12-281 was assessed in sensitized guinea pigs. AWD 12-281 (1.5 mg/kg i.t., 1-h pretreatment) inhibited allergen-induced bronchoconstriction by 68% (parameter airway resistance). In sensitized BP-2 mice AWD 12-281 abolished the allergen-induced bronchial hyperresponsiveness and eosinophilia in BALF, showing dose dependence. When given orally, i.v. or i.t. , AWD 12-281 has a considerably lower emetic potential than cilomilast in ferrets and roflumilast in pigs. When given topically by inhalation, no emesis could be induced in dogs up to the highest feasible dose (15 mg/kg in 50% lactose blend). These results indicate that AWD 12-281 is a unique potential new drug for the topical treatment of asthma and COPD.
High Sodium and Low Potassium Intake among Italian Children: Relationship with Age, Body Mass and Blood Pressure

Background Hypertension is the leading cause of death in developed countries and reduction of salt intake is recommended as a key preventive measure. Objective To assess the dietary sodium and potassium intakes in a national sample of Italian children and adolescents and to examine their relationships with BMI and blood pressure (BP) in the framework of the MINISAL survey, a program supported by the Italian Ministry of Health. Population and Methods The study population included 1424 healthy subjects (766 boys, 658 girls) aged 6-18 years (mean age: 10.1±2.9) who were consecutively recruited in participating National Health Service centers in 10 Italian regions. Electrolyte intake was estimated from 24 hour urine collections tested for completeness by the concomitant measurement of creatinine content. Anthropometric indices and BP were measured with standardized procedures. Results The average estimated sodium intake was 129 mmol (7.4 g of salt) per day among boys and 117 mmol (6.7 g of salt) among girls. Ninety-three percent of the boys and 89% of the girls had a consumption higher than the recommended age-specific standard dietary target. The estimated average daily potassium intakes were 39 mmol (1.53 g) and 36 mmol (1.40 g), respectively, over 96% of the boys and 98% of the girls having a potassium intake lower than the recommended adequate intake. The mean sodium/potassium ratio was similar among boys and girls (3.5 and 3.4, respectively) and over 3-fold greater than the desirable level. Sodium intake was directly related to age, body mass and BP in the whole population. Conclusions The Italian pediatric population is characterized by excessive sodium and deficient potassium intake. These data suggest that future campaigns should focus on children and adolescents as a major target in the framework of a population strategy of cardiovascular prevention.
WattDB: an energy-proportional cluster of wimpy nodes

The constant growth of data in all businesses leads to bigger database servers. While peak load times require fast and heavyweight hardware to guarantee performance, idle times are a waste of energy and money. Todays DBMSs have the ability to cluster several servers for performance and fault tolerance. Nevertheless, they do not support dynamic powering of the cluster's nodes based on the current workload. In this demo, we propose a newly developed DBMS running on clustered commodity hardware, which is able to dynamically power nodes. The demo allows the user to interact with the DBMS and adjust workloads, while the cluster's reaction is shown in real-time.
DISCOVERY OF ULTRA-FAST OUTFLOWS IN A SAMPLE OF BROAD-LINE RADIO GALAXIES OBSERVED WITH SUZAKU

We present the results of a uniform and systematic search for blueshifted Fe K absorption lines in the X-ray spectra of five bright broad-line radio galaxies observed with Suzaku. We detect, for the first time in radio-loud active galactic nuclei (AGNs) at X-rays, several absorption lines at energies greater than 7 keV in three out of five sources, namely, 3C 111, 3C 120, and 3C 390.3. The lines are detected with high significance according to both the F-test and extensive Monte Carlo simulations. Their likely interpretation as blueshifted Fe xxv and Fe xxvi K-shell resonance lines implies an origin from highly ionized gas outflowing with mildly relativistic velocities, in the range v ≃ 0.04–0.15c. A fit with specific photoionization models gives ionization parameters in the range log ξ ≃ 4–5.6 erg s−1 cm and column densities of NH ≃ 1022–1023 cm−2. These characteristics are very similar to those of the ultra-fast outflows (UFOs) previously observed in radio-quiet AGNs. Their estimated location within ∼0.01–0.3 pc of the central super-massive black hole suggests a likely origin related with accretion disk winds/outflows. Depending on the absorber covering fraction, the mass outflow rate of these UFOs can be comparable to the accretion rate and their kinetic power can correspond to a significant fraction of the bolometric luminosity and is comparable to their typical jet power. Therefore, these UFOs can play a significant role in the expected feedback from the AGN to the surrounding environment and can give us further clues on the relation between the accretion disk and the formation of winds/jets in both radio-quiet and radio-loud AGNs.
Optimized Nano-Slot Silicon Waveguide Structures for Optical Sensing Applications

In this paper, an investigation of optimized vertical and non-vertical nano-slot silicon waveguides with different cover media (cladding) is presented. The mode properties and light confining effects for both of these slot waveguides geometry are investigated at operating wavelength of 1550nm. Light propagation of waveguide modal profiles for electric field and intensity of such slot waveguides are also presented.