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Objective: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs

Abstract Obesity and type 2 diabetes are two closely related diseases representing a serious threat worldwide. An increase in metabolic rate through enhancement of non-shivering thermogenesis in adipose tissue may represent a potential therapeutic strategy. Nevertheless, a better understanding of thermogenesis transcriptional regulation is needed to allow the development of new effective treatments. Here, we aimed to characterize the specific transcriptomic response of white and brown adipose tissues after thermogenic induction. Using cold exposure to induce thermogenesis in mice, we identified mRNAs and miRNAs that were differentially expressed in several adipose depots. In addition, integration of transcriptomic data in regulatory networks of miRNAs and transcription factors allowed the identification of key nodes likely controlling metabolism and immune response. Moreover, we identified the putative role of the transcription factor PU.1 in the regulation of PPARγ-mediated thermogenic response of subcutaneous white adipose tissue. Therefore, the present study provides new insights into the molecular mechanisms that regulate non-shivering thermogenesis.

Inertial measurement units (IMUs) are key components of various applications including navigation, robotics, aerospace, and automotive systems. IMU sensor characteristics have a significant impact on the accuracy and reliability of these applications. In particular, noise characteristics and bias stability are critical for proper filter settings to perform a combined GNSS/IMU solution. This paper presents an analysis based on the Allan deviation of different IMU sensors that correspond to different grades of micro-electromechanical systems (MEMS)-type IMUs in order to evaluate their accuracy and stability over time. The study covers three IMU sensors of different grades (ascending order): Rokubun Argonaut navigator sensor (InvenSense TDK MPU9250), Samsung Galaxy Note10 phone sensor (STMicroelectronics LSM6DSR), and NovAtel PwrPak7 sensor (Epson EG320N). The noise components of the sensors are computed using overlapped Allan deviation analysis on data collected over the course of a week in a static position. The focus of the analysis is to characterize the random walk noise and bias stability, which are the most critical for combined GNSS/IMU navigation and may differ or may not be listed in manufacturers’ specifications. Noise characteristics are calculated for the studied sensors and examples of their use in loosely coupled GNSS/IMU processing are assessed. This work proposes a structured and reproducible approach for working with sensors for their use in navigation tasks in combination with GNSS, and can be used for sensors of different levels to supplement missing or incorrect sensor manufacturers’ data.

Type 2 diabetes, insulin resistance, and obesity are strongly associated and are a major health problem worldwide. Obesity largely results from a sustained imbalance between energy intake and expenditure. Therapeutic approaches targeting metabolic rate may counteract body weight gain and insulin resistance. Bone morphogenic protein 7 (BMP7) has proven to enhance energy expenditure by inducing non-shivering thermogenesis in short-term studies in mice treated with the recombinant protein or adenoviral vectors encoding BMP7. To achieve long-term BMP7 effects, the use of adeno-associated viral (AAV) vectors would provide sustained production of the protein after a single administration. Here, we demonstrated that treatment of high-fat-diet-fed mice and ob/ob mice with liver-directed AAV-BMP7 vectors enabled a long-lasting increase in circulating levels of this factor. This rise in BMP7 concentration induced browning of white adipose tissue (WAT) and activation of brown adipose tissue, which enhanced energy expenditure, and reversed WAT hypertrophy, hepatic steatosis, and WAT and liver inflammation, ultimately resulting in normalization of body weight and insulin resistance. This study highlights the potential of AAV-BMP7-mediated gene therapy for the treatment of insulin resistance, type 2 diabetes, and obesity.

Mucopolysaccharidosis type IVA (MPSIVA) is a lysosomal storage disorder causing severe skeletal and non-skeletal alterations in patients. Here, the authors generate a MPSIVA rat model that mimics the disabling human pathology and develop an AAV9-Galns gene therapy to treat the disease.

This paper presents a new way of combining Abel inversion and the Chapman model with a linearly increasing scale height to retrieve ionospheric electron density vertical profiles from truncated-sounding radio-occultation data. A linear Vary–Chap model is used to cover the blind region due to data truncation, with parameters estimated by enumeration of the possible values in a grid centered around a set of parameters compatible with ionospheric physics. The resulting electron density is estimated with its corresponding error from the linear least-squares solution presenting the smaller post-fit residual on the input GNSS carrier-phase measurements. The results, tested on a set of representative GNSS RO measurements obtained by COSMIC/FORMOSAT-3, show that this method can retrieve EDVPs with a predominant absolute and relative error of 1010e−m−3 and 5%, respectively, and in less than 10 s per profile, which makes this method suitable for near real-time applications in upcoming missions such as EUMETSAT Polar System-Second Generation.

Abstract Prevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity. Native FGF21 has, however, poor pharmacokinetic properties, making gene therapy an attractive strategy to achieve sustained circulating levels of this protein. Here, adeno‐associated viral vectors (AAV) were used to genetically engineer liver, adipose tissue, or skeletal muscle to secrete FGF21. Treatment of animals under long‐term high‐fat diet feeding or of ob/ob mice resulted in marked reductions in body weight, adipose tissue hypertrophy and inflammation, hepatic steatosis, inflammation and fibrosis, and insulin resistance for > 1 year. This therapeutic effect was achieved in the absence of side effects despite continuously elevated serum FGF21. Furthermore, FGF21 overproduction in healthy animals fed a standard diet prevented the increase in weight and insulin resistance associated with aging. Our study underscores the potential of FGF21 gene therapy to treat obesity, insulin resistance, and T2D.

WiFi Round Trip Time (RTT) unlocks meter level accuracies in user terminal positions where no other navigation systems, such as Global Navigation Satellite Systems (GNSS), are able to (e.g., indoors). However, little has been done so far to obtain a scalable and automated system that computes the position of the WiFi Access Points (WAP) using RTT and that is able to estimate, in addition to the position, the hardware biases that offset the WiFi ranging measurements. These biases have a direct impact on the ultimate position accuracy of the terminals. This work proposes a method in which the computation of the WiFi Access Points positions and hardware biases (i.e., products) can be estimated based on the ranges and position fixes provided by user terminals (i.e., inverse positioning) and details how this can be improved if raw GNSS measurements (pseudoranges and carrier phase) are also available in the terminal. The data setup used to obtain a performance assessment was configured in a benign scenario (open sky with no obstructions) in order to obtain an upper boundary on the positioning error that can be achieved with the proposed method. Under these conditions, accuracies better than 1.5 m were achieved for the WAP position and hardware bias. The proposed method is suitable to be implemented in an automated manner, without having to rely on dedicated campaigns to survey 802.11mc-compliant WAPs. This paper offers a technique to automatically estimate both mild-indoor WAP products (where terminals have both Wi-Fi RTT and GNSS coverage) and deep-indoor WAP (with no GNSS coverage where the terminals obtain their position exclusively from previously estimated mild-indoor WAPs).

Abstract  Phase center variations of the receiver and transmitter antenna constitute a remaining uncertainty in the high precision orbit determination (POD) of low Earth orbit (LEO) satellites using GPS measurements. Triggered by the adoption of absolute phase patterns in the IGS processing standards, a calibration of the Sensor Systems S67-1575-14 antenna with GFZ choke ring has been conducted that serves as POD antenna on various geodetic satellites such as CHAMP, GRACE and TerraSAR-X. Nominal phase patterns have been obtained with a robotic measurement system in a field campaign and the results were used to assess the impact of receiver antenna phase patterns on the achievable positioning accuracy. Along with this, phase center distortions in the actual spacecraft environment were characterized based on POD carrier phase residuals for the GRACE and TerraSAR-X missions. It is shown that the combined ground and in-flight calibration can improve the carrier phase modeling accuracy to a level of 4 mm which is close to the pure receiver noise. A 3.5 cm (3D rms) consistency of kinematic and reduced dynamic orbit determination solutions is achieved for TerraSAR-X, which presumably reflects the limitations of presently available GPS ephemeris products. The reduced dynamic solutions themselves match the observations of high grade satellite laser ranging stations to 1.5 cm but are potentially affected by cross-track biases at the cm-level. With respect to the GPS based relative navigation of TerraSAR-X/TanDEM-X formation, the in-flight calibration of the antenna phase patterns is considered essential for an accurate modeling of differential carrier phase measurements and a mm level baseline reconstruction. [ABSTRACT FROM AUTHOR]

In late December 2005 the GIOVE-A test satellite was launched by the European Space Agency (ESA) to secure the frequencies for the Galileo system and to provide a platform for testing the new navigation signals. We performed an initial assessment of these signals using the 30 m deep space antenna of the DLR ground station in Weilheim (Germany). The antenna gain raised the signals above the noise level, thus allowing a detailed analysis even without knowledge of the ranging codes. The present paper covers the analysis of the L1/E1 signals, which includes a discussion of the spectrum, the time domain signal and a decoding of the spreading codes for the Open Service. [ABSTRACT FROM AUTHOR]

En este trabajo presentamos una propuesta entorno a cómo se puede utilizar la Descomposición en valores singulares de una matriz para desarrollar un temario de una asignatura de Álgebra lineal en un grado de ingeniería. Para ello introducimos algunas técnicas especiales, resultados y ejemplos.