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Noonan syndrome (NS) is a Mendelian phenotype, member of a group of disorders sharing neurocardiofaciocutaneous involvement, known as RASopathies, caused by germline variants in genes coding for components of the RAS/MAPK signaling pathway. Recently, a novel gene of the RAS family (MRAS) was reported to be associated with NS in five children, all of them presenting, among the cardinal features of NS, the same cardiac finding, hypertrophic cardiomyopathy (HCM). We report on a 2-month-old infant boy also presenting this cardiac anomaly that evolved to a fatal outcome after a surgical myectomy. In addition, a thick walled left ventricle apical aneurysm, rarely described in NS, was also disclosed. Next-generation sequencing revealed a missense, previously reported variant in MRAS (p.Thr68Ile). This report reinforces the high frequency of HCM among individuals harboring MRAS variants, contrasting to the 20% overall prevalence of this cardiac anomaly in NS. Thus, these preliminary data suggest that variants in MRAS per se are high risk factors for the development of an early, severe HCM, mostly of them with left ventricle outflow tract obstruction, with poor prognosis. Because of the severity of the cardiac involvement, other clinical findings could not be addressed in detail. Therefore, long-term follow-up of these individuals and further descriptions are required to fully understand the complete phenotypic spectrum of NS associated with MRAS germline variants, including if these individuals present an increased risk for cancer.

This paper empirically tests how the magnitude of trade promotion effects of mutual recognition agreements (MRAs) varies with various mediums. The main rationale for the research is that because an MRA eliminates technical barriers to trade (TBT), the trade promotion effects of MRAs are inversely much stronger if TBT originally restricted trade before their entry into force. Using data on MRAs and international trade in 34 countries and 22 manufacturing sectors covering 1995 to 2009, the paper empirically shows that the trade promotion effects of MRAs can be much stronger, depending on the type of contract, time period after the entry into force, components of exports, and country and industry characteristics such as technology level and global competitiveness. The results will provide insight for policy makers and stakeholders who cooperate with foreign countries in various regulations, especially in developing countries that have low levels of technology, competitiveness, and regulatory governance capacity.

We propose a new way to enlarge gain bandwidth of a miniaturized reflectarray antenna (MRA), a new type of reflectarray antenna (RA) with significantly reduced volume. To extend the gain bandwidth, we have used meander-line based sub-wavelength elements as reflectarray cells, which can fully cover a required reflection phase range ideally, 360°. As a result, we have accomplished a three times wider gain bandwidth than that of our previous MRAs. In addition, the proposed MRA can also provide high gain with good aperture efficiency even though a main beam directs toward a tilted direction. Furthermore, remarkably reduced electrical volume, which is 700 times smaller than the smallest conventional RAs, is still maintained. Measured aperture efficiency of the proposed MRA is 41.1% which is comparable with conventional RAs. And the measurement results show that the main lobe direction is very stable around the target direction within the given −1 dB gain bandwidth without any degradation in other performances. As a result, the proposed MRAs with wide gain bandwidth stands out as a good alternative of the conventional RAs.

The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole‐exome and whole‐genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer‐relevant genes in Type IV, we performed whole‐exome sequencing and genome‐wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein‐coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin‐like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets.

Purpose To achieve high temporal and spatial resolution for contrast-enhanced time-resolved MR angiography exams (trMRAs), fast imaging techniques such as non-Cartesian parallel imaging must be used. In this study, the three-dimensional (3D) through-time radial generalized autocalibrating partially parallel acquisition (GRAPPA) method is used to reconstruct highly accelerated stack-of-stars data for time-resolved renal MRAs. Materials and Methods Through-time radial GRAPPA has been recently introduced as a method for non-Cartesian GRAPPA weight calibration, and a similar concept can also be used in 3D acquisitions. By combining different sources of calibration information, acquisition time can be reduced. Here, different GRAPPA weight calibration schemes are explored in simulation, and the results are applied to reconstruct undersampled stack-of-stars data. Results Simulations demonstrate that an accurate and efficient approach to 3D calibration is to combine a small number of central partitions with as many temporal repetitions as exam time permits. These findings were used to reconstruct renal trMRA data with an in-plane acceleration factor as high as 12.6 with respect to the Nyquist sampling criterion, where the lowest root mean squared error value of 16.4% was achieved when using a calibration scheme with 8 partitions, 16 repetitions, and a 4 projection × 8 read point segment size. Conclusion 3D through-time radial GRAPPA can be used to successfully reconstruct highly accelerated non-Cartesian data. By using in-plane radial undersampling, a trMRA can be acquired with a temporal footprint less than 4s/frame with a spatial resolution of approximately 1.5 mm × 1.5 mm × 3 mm. J. Magn. Reson. Imaging 2014;40:864–874. © 2014 Wiley Periodicals, Inc.

The authors have studied the statistical characteristics of China's molybdenum deposits to establish the grade-tonnage model based on the data updated to the end of 2010. The results showed that each type of China's molybdenum deposits complied with Lasky's law approximately and the characteristics of grade-tonnage model obey the lognormal distribution. However, there are poor correlations between grade and tonnage respectively. Ultimately, we aimed to fit the grade-tonnage model through the known distribution function, draw the cumulative probability curves, and evaluated undiscovered mineral resources of China's molybdenum deposits by means of Monte Carlo simulation integrated in MRAS.

A new motion corrected Time-of-Flight MRA technique named Variable Pitch PROPELLER is presented. This technique employs the PROPELLER acquisition and reconstruction scheme for in-plane bulk motion correction. A non- Fourier through-plane encoding mechanism called quadratic encoding boosts SNR, relative to conventional 2D MRA, in lieu of traditional 3D encoding. Partial Fourier encoding is applied in the slice direction for a further reduction in scan time. This work details the construction and optimization of this technique. VPPROP MRAs are compared with a clinical MOTSA protocol. Initial results show promising robustness to bulk motion effects. The comparisons with MOTSA provide insight as to the additions required to create a comparable scan.

Complying with global standards and technical norms can be costly, making them potential impediments to trade, but it can also expand export opportunities. Two policies available to governments are alignment of domestic technical regulations with international standards and entry into mutual recognition agreements (MRAs). We study the effects of such decisions on the volume of exports to developed markets by firms in developing countries, using data from a World Bank firm-level survey of awareness of global product norms. Both standards alignment and MRAs are associated with more exports to developed countries, but only MRAs significantly promote exports. This finding is consistent with theoretical predictions that MRAs should reduce the fixed costs of exporting more than standards alignment, permitting more firms to enter export markets in higher volumes. Governments in developing countries hoping to encourage exports may wish to favour the negotiation of mutual recognition of testing and certification procedures with major trading partners as a more affirmative avenue to expanding international sales.

Mandibular repositioning appliances (MRAs) reduce symptoms of obstructive sleep apnoea in the short term, but the long-term effects are unknown. Our objective was to evaluate the long-term symptomatic effects of custom-made MRAs and to identify the patients who will experience subjective benefits from treatment. A cohort of 260 consecutive patients treated with appliances for non-apnoeic snoring or sleep apnoea was followed up by a questionnaire and examination after an average of 5.4 years. The subjective effect was defined as good when complaints of daytime sleepiness occurred less than once a week. A total of 185 patients (71%) responded to the questionnaires. Of the respondents, 96 reported frequent use, 33 reported infrequent use, 26 reported discontinued treatment and 30 reported modified treatment. Mild cases (apnoea-hypopnoea index [AHI] < 15) were likelier than more severe cases to continue treatment. Patients who had used MRAs reported fewer complaints of sleepiness, headaches and daytime naps. Frequent use (P = 0.001), few night-time awakenings before start of treatment (P = 0.02) and effective apnoea reduction during treatment of more severe cases (P = 0.02) correlated with a good subjective effect at long-term follow-up. Our conclusion is that custom-made MRAs reduce sleep apnoea symptoms in the long term. The mildest cases will experience the greatest long-term benefit. The reason is that non-apnoeic snorers and patients with a mild disease are more likely to continue treatment and that their long-term results with regard to excessive sleepiness are similar to patients with a more severe disease.

A frequently applied method of speed-sensorless rotor flux oriented control of induction machines relies on utilisation of model reference adaptive system (MRAS) based speed estimation, where the outputs of the reference and the adjustable model are selected as rotor flux space phasors. Accuracy of the method heavily depends on correct setting of the machine parameters and adjustment of the filter and PI controller parameters within the estimator. The paper at first describes tuning of various parameters of the estimator, using purely experimental data. The speed estimator is operated in parallel with a commercially available rotor flux oriented induction motor drive with speed sensor and sampled stator voltages and currents are used to tune induction motor parameters, various filters and the PI controller within the estimator. The procedure is described and illustrated using a comparison between the measured actual speed response during acceleration transients and the corresponding speed estimate obtained from the speed estimator. In the second part of the paper, speed estimation error that will take place in the base speed region due to incorrect setting and/or variation of the parameters of the machine (stator resistance, rotor resistance and magnetising inductance) within the speed estimator is assessed using experimentally recorded data. The experimental results are found to be in very good agreement with previously published theoretical results.

This paper proposes a novel MRAS-based speed controller for the induction motor drive without shaft sensor, with the integral adaptation mechanism for on-line tuning of the stator resistance (R s ). For an accurate estimate of the shaft speed (ω) even at near zero speeds, proposed R s estimator running parallel in order to compensate for the R s thermal variation. In an intent to accurately estimate the ω at low speeds, without deterioration the drive performance, parallel with the ω estimation the R s is also estimated to compensate R s thermal variation. The reference and adjustable models of MRAS-based ω estimator change their roles in the R s estimator context. The dynamics of the ω derivation and the R s estimation are investigated for a wide range of operating conditions and straightforward design procedure is proposed, derived from the hyperstability theory. Extensive computer simulations prove the effectiveness of the proposed solution.

Recently, multiphase machines have been promoted as competitors to their three-phase counterparts in high-power safety-critical drive applications. Among numerous advantages of multiphase induction machine (IM) drives, self-starting and operation under open phase(s) stand as the most salient features. With open phase(s), optimal current control provides disturbance- free operation given a set of objective functions. Although hysteresis current control was merely employed in the literature as it offers a simple controller structure to control the remaining healthy phases, it is not suitable for high-power applications. In the literature, multiple synchronous reference frame (dq) control can be an alternative; however, it requires back and forth transformations with several calculations and additional sophistication. In this paper, a simple technique employing adaptive proportional resonant (PR) current controllers is presented to control a five-phase IM under open-phase conditions. Results for both volt/hertz (V/f) and field oriented control (FOC) systems are presented. Moreover, sensorless operation under fault condition is also demonstrated by estimating the machine speed using a rotor flux-based model reference adaptive system (MRAS) speed estimator. The proposed controllers are experimentally verified and compared. Although FOC provides better dynamic performance, V/f control offers a simpler control structure and a lower number of PR controllers.

To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice. The ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5 with acute HF and 59.5 with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, reninangiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0 of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4 of the cases, respectively. About 30 of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues. This pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written.

This paper discusses the estimation of a parameter in an autoregressive model with infinite variance. A recursive estimation procedure based on minimizing the prediction errors is provided. It is also shown that the model reference adaptive system estimate for an AR (1) model given in Aase (1983) is a special case.

Vector-controlled induction motor drive systems without speed sensors have been widely studied. Speed estimation can be treated as a problem of parameter estimation under the theory of MRAS (model reference adaptive systems). In such cases, the convergence and robustness of the system are major issues. In this paper, we discuss the stability of an MRAS, that includes a full-order adaptive observer of the induction motor and is used for estimating the rotor speed and identifying the stator resistance. It is verified that, under some conditions, the transfer matrix in the forward path of the MRAS is strictly positive-real and that the non-linear block in the feedback path satisfies Popov's criterion. As a result, the system is hyperstable. The influence of the set error of the rotor resistance is discussed and the design criterion for the feedback gain of the observer is presented. Finally, the system is linearized for the parameter design of the speed estimator.

This paper describes a new scheme for the speed sensorless control of the vector-controlled induction motor drive. Based on the model reference adaptive system (MRAS) theory, the rotor speed of the induction machine is estimated with a full-order adaptive observer. The estimated speed then is used as the signal for the vector control and the speed control. To accurately estimate the speed at the lower speed range, the value of the stator resistance also is identified at the same time and then is used to modify the resistance value set in the observer. The resulting system is verified to be hyperstable with Popov's criterion. As a result, this drive can operate stably in a wide range of speed even at zero speed. Also, it is shown theoretically that neither speed nor resistance of the rotor can be identified at the same time because these two parameters are dependent on each other. Simulation results and experiments also show that the scheme is effective.

The SM (superconducting magnet) current feedback control of I-C unit (inductor-converter unit) has to be designed to maintain stability, considering that the time constant of transfer function from SM current to SM terminal voltage is very large. For accurate control, it is also very important to take into account the current and magnetic field distributions inside the SM, ac loss and stray capacitances between coils. In this paper, direct digital control systems such as PID system, first-order time lag system with dead time element, finite time setting control system (FTSC) and model reference adaptive control system (MRAS) are proposed. Control characteristics of these control systems are analyzed by experiment and simulation.