The Laboratory Diagnosis of Malaria: A Focus on the Diagnostic Assays in Non-Endemic Areas.

Even if malaria is rare in Europe, it is a medical emergency and programs for its control should ensure both an early diagnosis and a prompt treatment within 24-48 h from the onset of the symptoms. The increasing number of imported malaria cases as well as the risk of the reintroduction of autochthonous cases encouraged laboratories in non-endemic countries to adopt diagnostic methods/algorithms. Microscopy remains the gold standard, but with limitations. Rapid diagnostic tests have greatly expanded the ability to diagnose malaria for rapid results due to simplicity and low cost, but they lack sensitivity and specificity. PCR-based assays provide more relevant information but need well-trained technicians. As reported in the World Health Organization Global Technical Strategy for Malaria 2016-2030, the development of point-of-care testing is important for the improvement of diagnosis with beneficial consequences for prompt/accurate treatment and for preventing the spread of the disease. Despite their limitations, diagnostic methods contribute to the decline of malaria mortality. Recently, evidence suggested that artificial intelligence could be utilized for assisting pathologists in malaria diagnosis.

Benefit of high-dose oral riboflavin therapy in riboflavin transporter deficiency.

Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation is beneficial in short-term reports, but the quantum of benefit in various clinical domains is not well understood. A PubMed search was conducted, which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow-up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed. Seventy-six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%) and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy dependent. Riboflavin supplementation is a lifesaving intervention for patients with RTD and results in a profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease-modifying therapies.

Research on a Time Difference Processing Method for RTD-Fluxgate Data Based on the Combination of the Mahalanobis Distance and Group Covariance.

During the measurement of magnetic fields, Residence Time Difference (RTD)-fluxgate sensors suffer from abnormal time difference jumps due to the random interference of magnetic core noise and environmental noise, which results in gross errors. This situation restricts the improvement of sensor accuracy and stability. In order to solve the above problems efficiently, a time difference gross error processing method based on the combination of the Mahalanobis distance (MD) and group covariance is presented in this paper, and the processing effects of different methods are compared and analyzed. The results of the simulation and experiment indicate that the proposed method is more advantageous in identifying the gross error in time difference. The signal-to-noise ratio for the time difference is improved by about 34 times, while the fluctuation of the Negative Magnetic Saturation Time (NMST) ΔTNMST is reduced by 95.402%, which significantly reduces the fluctuation of time difference and effectively improves the accuracy and stability of the sensor.

Direct Fabrication of a Copper RTD over a Ceramic-Coated Stainless-Steel Tube by Combination of Magnetron Sputtering and Sol-Gel Techniques.

Reducing the economic and environmental impact of industrial process may be achieved by the smartisation of different components. In this work, tube smartisation is presented via direct fabrication of a copper (Cu)-based resistive temperature detector (RTD) on their outer surfaces. The testing was carried out between room temperature and 250 °C. For this purpose, copper depositions were studied using mid-frequency (MF) and high-power impulse magnetron sputtering (HiPIMS). Stainless steel tubes with an outside inert ceramic coating were used after giving them a shot blasting treatment. The Cu deposition was performed at around 425 °C to improve adhesion as well as the electrical properties of the sensor. To generate the pattern of the Cu RTD, a photolithography process was carried out. The RTD was then protected from external degradation by a silicon oxide film deposited over it by means of two different techniques: sol-gel dipping technique and reactive magnetron sputtering. For the electrical characterisation of the sensor, an ad hoc test bench was used, based on the internal heating and the external temperature measurement with a thermographic camera. The results confirm the linearity (R2 > 0.999) and repeatability in the electrical properties of the copper RTD (confidence interval < 0.0005).

Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis.

Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts the activity of numerous isodecoders in metazoans; and leads to human diseases. To comprehensively define the effects of sequence variation on tRNA function, we developed a high-throughput in vivo screen to quantify the activity of a model tRNA, the nonsense suppressor SUP4oc of Saccharomyces cerevisiae. Using a highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting of a library of SUP4oc mutant yeast strains, and deep sequencing, we scored 25,491 variants. Unexpectedly, SUP4oc tolerates numerous sequence variations, accommodates slippage in tertiary and secondary interactions, and exhibits genetic interactions that suggest an alternative functional tRNA conformation. Furthermore, we used this methodology to define tRNA variants subject to rapid tRNA decay (RTD). Even though RTD normally degrades tRNAs with exposed 5' ends, mutations that sensitize SUP4oc to RTD were found to be located throughout the sequence, including the anti-codon stem. Thus, the integrity of the entire tRNA molecule is under surveillance by cellular quality control machinery. This approach to assess activity at high throughput is widely applicable to many problems in tRNA biology.

Challenges and Potential to Revamp the Normative Framework on the Right to Development.

The world is currently at an ebb for realizing the Right to Development. Weakening multilateralism, de-globalization, the COVID-19 pandemic and inertia to reform international governance are among the multitude of reasons for this phenomenon. However, the need for a better, more inclusive and greener recovery, and the efforts necessary to attain the 2030 Agenda have provided the international community an opportunity to reinvigorate its realization. This article reviews the international discourse on the Right to Development and provides recommendations on the way forward to revitalize its implementation at the 35th anniversary of the related Declaration.

In vivo manipulation of muscle shape and tendinous stiffness affects the human ability to generate torque rapidly.

NEW FINDINGS: What is the central question of this study? What are the determinants of muscle belly gearing, and how does it affect the torque rise? What is the main finding and its importance? Change in muscle thickness of the gastrocnemius medialis is related to variations in belly gearing. Belly gearing has a key role in the rise of muscle torque and rate of torque development (RTD). Besides, the increase of tendinous tissue stiffness could increase the torque rise as well, and in turn, the RTD. However, changes in the tendinous tissue stiffness showed no effects on muscle fascicle behaviour, suggesting a possible uncoupling between muscle and tendon mechanical properties. ABSTRACT: During fixed-end contractions, muscles bulge in thickness and/or width to maintain a constant volume, whereas tendons lengthen over the entire contraction period. These dynamic changes play a key functional role in modulating the generated torque. However, the literature has revealed a limited understanding of in vivo dynamic muscle-tendon changes during rapid contractions. Therefore, this study aimed to investigate the determinants of belly gearing (belly velocity/fascicle velocity) and its effects on rapid torque production during in vivo fixed-end contractions. Twenty healthy males were recruited for the study. Muscle shape and tendon stiffness were manipulated by applying a transverse load (2-10 kg) and an ankle rotation manoeuvre, respectively. Ultrafast-ultrasound was employed to quantify medial gastrocnemius architecture during evoked contraction and a dynamometer was used to measure the muscle torque and quantify the rate of torque development (RTD). Torque and RTD diminished by transverse load application, whereas they increased during the ankle rotation manoeuvre. Belly gearing declined with increasing transverse load but was unaffected by tendinous stiffness variations. Alterations in belly gearing were strongly related to variations in muscle thickness throughout any load applied and affected the torque rise rapidly. In contrast, changes in tendinous tissue stiffness affected the torque rise only but did not modify the muscle shape. These data may suggest that concurrent manipulation of the tendinous tissue stiffness and muscle shape does not affect the explosive rise in torque capacity, suggesting a possible uncoupling between mechanical properties of muscle and tendon.

Perception of effort during an isometric contraction is influenced by prior muscle lengthening or shortening.

PURPOSE: Following a shortening or lengthening muscle contraction, torque produced in the isometric steady state is lower (residual torque depression; rTD) or higher (residual torque enhancement; rTE), respectively, compared to a purely isometric contraction at the same final muscle length and level of activation. This is referred to as the history dependence of force. When matching a given torque level, there is greater muscle activation (electromyography; EMG) following shortening and less activation following lengthening. Owing to these differences in neuromuscular activation, it is unclear whether perception of effort is altered by the history dependence of force during plantar-flexion. METHODS: Experiment 1 tested whether perception of effort differed between the rTD and rTE state when torque was matched. Experiment 2 tested whether perception of effort differed between the rTD and rTE state when EMG was matched. Finally, experiment 3 tested whether EMG differed between the rTD and rTE state when perception of effort was matched. RESULTS: When torque was matched, both EMG and perception of effort were higher in the rTD compared to rTE state. When EMG was matched, torque was lower in the rTD compared to rTE state while perception of effort did not differ between the two states. When perception of effort was matched, torque was lower in the rTD compared to rTE state and EMG did not differ between the two states. CONCLUSION: The combined results from these experiments indicate that the history dependence of force alters one's perception of effort, dependent on the level of motor command.

Lead-Wire-Resistance Compensation Technique Using a Single Zener Diode for Two-Wire Resistance Temperature Detectors (RTDs).

In remote measurement systems, the lead wire resistance of the resistance sensor will produce a large measurement error. In order to ensure the accuracy of remote measurement, a novel lead-wire-resistance compensation technique is proposed, which is suitable for a two-wire resistance temperature detector. By connecting a zener diode in parallel with the resistance temperature detector (RTD) and an interface circuit specially designed for it, the lead-wire-resistance value can be accurately measured by virtue of the constant voltage characteristic of the zener diode when reverse breakdown occurs, and compensation can thereby be made when calculating the resistance of RTD. Through simulation verification and practical circuit testing, when the sensor resistance is in 848-2120 Ω scope and the lead wire resistance is less than 50 Ω, the proposed technology can ensure the measuring error of the sensor resistance within ±1 Ω and the temperature measurement error within ±0.3 °C for RTDs performing 1000 Ω at 0 °C. Therefore, this method is able to accurately compensate the measurement error caused by the lead wire resistance in two-wire RTDsand is suitable for most applications.

Design and Integration of a Wireless Stretchable Multimodal Sensor Network in a Composite Wing.

This article presents the development of a stretchable sensor network with high signal-to-noise ratio and measurement accuracy for real-time distributed sensing and remote monitoring. The described sensor network was designed as an island-and-serpentine type network comprising a grid of sensor "islands" connected by interconnecting "serpentines." A novel high-yield manufacturing process was developed to fabricate networks on recyclable 4-inch wafers at a low cost. The resulting stretched sensor network has 17 distributed and functionalized sensing nodes with low tolerance and high resolution. The sensor network includes Piezoelectric (PZT), Strain Gauge (SG), and Resistive Temperature Detector (RTD) sensors. The design and development of a flexible frame with signal conditioning, data acquisition, and wireless data transmission electronics for the stretchable sensor network are also presented. The primary purpose of the frame subsystem is to convert sensor signals into meaningful data, which are displayed in real-time for an end-user to view and analyze. The challenges and demonstrated successes in developing this new system are demonstrated, including (a) developing separate signal conditioning circuitry and components for all three sensor types (b) enabling simultaneous sampling for PZT sensors for impact detection and (c) configuration of firmware/software for correct system operation. The network was expanded with an in-house developed automated stretch machine to expand it to cover the desired area. The released and stretched network was laminated into an aerospace composite wing with edge-mount electronics for signal conditioning, processing, power, and wireless communication.

Antioxidant Amelioration of Riboflavin Transporter Deficiency in Motoneurons Derived from Patient-Specific Induced Pluripotent Stem Cells.

Mitochondrial dysfunction is a key element in the pathogenesis of neurodegenerative disorders, such as riboflavin transporter deficiency (RTD). This is a rare, childhood-onset disease characterized by motoneuron degeneration and caused by mutations in SLC52A2 and SLC52A3, encoding riboflavin (RF) transporters (RFVT2 and RFVT3, respectively), resulting in muscle weakness, ponto-bulbar paralysis and sensorineural deafness. Based on previous findings, which document the contribution of oxidative stress in RTD pathogenesis, we tested possible beneficial effects of several antioxidants (Vitamin C, Idebenone, Coenzyme Q10 and EPI-743, either alone or in combination with RF) on the morphology and function of neurons derived from induced pluripotent stem cells (iPSCs) from two RTD patients. To identify possible improvement of the neuronal morphotype, neurite length was measured by confocal microscopy after ß-III tubulin immunofluorescent staining. Neuronal function was evaluated by determining superoxide anion generation by MitoSOX assay and intracellular calcium (Ca2+) levels, using the Fluo-4 probe. Among the antioxidants tested, EPI-743 restored the redox status, improved neurite length and ameliorated intracellular calcium influx into RTD motoneurons. In conclusion, we suggest that antioxidant supplementation may have a role in RTD treatment.

Development of Novel Experimental Models to Study Flavoproteome Alterations in Human Neuromuscular Diseases: The Effect of Rf Therapy.

Inborn errors of Riboflavin (Rf) transport and metabolism have been recently related to severe human neuromuscular disorders, as resulting in profound alteration of human flavoproteome and, therefore, of cellular bioenergetics. This explains why the interest in studying the "flavin world", a topic which has not been intensively investigated before, has increased much over the last few years. This also prompts basic questions concerning how Rf transporters and FAD (flavin adenine dinucleotide) -forming enzymes work in humans, and how they can create a coordinated network ensuring the maintenance of intracellular flavoproteome. The concept of a coordinated cellular "flavin network", introduced long ago studying humans suffering for Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), has been, later on, addressed in model organisms and more recently in cell models. In the frame of the underlying relevance of a correct supply of Rf in humans and of a better understanding of the molecular rationale of Rf therapy in patients, this review wants to deal with theories and existing experimental models in the aim to potentiate possible therapeutic interventions in Rf-related neuromuscular diseases.

An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency.

Riboflavin transporter deficiency (RTD) is a rare neurological condition that encompasses the Brown-Vialetto-Van Laere and Fazio-Londe syndromes since the discovery of pathogenic mutations in the SLC52A2 and SLC52A3 genes that encode human riboflavin transporters RFVT2 and RFVT3. Patients present with a deteriorating progression of peripheral and cranial neuropathy that causes muscle weakness, vision loss, deafness, sensory ataxia, and respiratory compromise which when left untreated can be fatal. Considerable progress in the clinical and genetic diagnosis of RTDs has been made in recent years and has permitted the successful lifesaving treatment of many patients with high dose riboflavin supplementation. In this review, we first outline the importance of riboflavin and its efficient transmembrane transport in human physiology. Reports on 109 patients with a genetically confirmed diagnosis of RTD are then summarized in order to highlight commonly presenting clinical features and possible differences between patients with pathogenic SLC52A2 (RTD2) or SLC52A3 (RTD3) mutations. Finally, we focus attention on recent work with different models of RTD that have revealed possible pathomechanisms contributing to neurodegeneration in patients.

A New Submersion Detection Sensor Using Two Resistance Temperature Detectors Operating on the Thermal Equilibrium Principle.

In this study, a new submersion detection sensor with improved reliability and stability is proposed. The new sensor uses two Resistance Temperature Detectors (RTDs) and operates on the thermal equilibrium principle. The submersion detection sensor controls two RTDs that maintain a constant temperature difference between them in the surrounding environment. The first RTD is used as a reference sensor to measure ambient temperature and the second RTD is supplied with higher current than the reference sensor for self-heating. When submerged, because the thermal conductivity and convective heat transfer coefficient of water are higher than that of air, the temperature difference between the two RTDs is lower in water than in air based on the thermal equilibrium principle. Under these conditions, a submersion detector with a signal conditioning circuit detects these temperature differences. The static performance of the proposed sensor was evaluated by checking whether malfunctions occurred at varying ambient temperatures, differing humidities, and when there was rainfall. In addition, the dynamic performance was evaluated using the response time at varying ambient air temperatures before submersion and with changing water temperatures after submersion, as a metric. The proposed submersion detection sensor is expected to find useful application in aircrafts, ships, and various other industrial fields.

Flexible Temperature Sensor Integration into E-Textiles Using Different Industrial Yarn Fabrication Processes.

Textiles enhanced with thin-film flexible sensors are well-suited for unobtrusive monitoring of skin parameters due to the sensors' high conformability. These sensors can be damaged if they are attached to the surface of the textile, also affecting the textiles' aesthetics and feel. We investigate the effect of embedding flexible temperature sensors within textile yarns, which adds a layer of protection to the sensor. Industrial yarn manufacturing techniques including knit braiding, braiding, and double covering were utilised to identify an appropriate incorporation technique. The thermal time constants recorded by all three sensing yarns was <10 s. Simultaneously, effective sensitivity only decreased by a maximum of 14% compared to the uncovered sensor. This is due to the sensor being positioned within the yarn instead of being in direct contact with the measured surface. These sensor yarns were not affected by bending and produced repeatable measurements. The double covering method was observed to have the least impact on the sensors' performance due to the yarn's smaller dimensions. Finally, a sensing yarn was incorporated in an armband and used to measure changes in skin temperature. The demonstrated textile integration techniques for flexible sensors using industrial yarn manufacturing processes enable large-scale smart textile fabrication.

Designing process and operational effect of modified septic tank for the pre-treatment of rural domestic sewage.

Structure and performance of a newly designed four-chamber septic tank were investigated in current study. A three-layer orifice plate was fitted in the first compartment in an upward direction, and a baffle was arranged in the second compartment of the septic tank. The filter placed in the third and fourth compartment was used to collect water for field irrigation or connect subsequent devices for further processing. Flow field distribution in the first chamber was numerically simulated by Fluent software, and simulation results were verified by residence time distribution tracer experiment. The improved treatment effects of the modified septic tank with optimal parameters of 20 mm (diameter), 60 mm (gap) and 180 mm (distance) were validated by simulation experiments. High removal rates of chemical and biological oxygen demand reflected the effectiveness of modified septic tanks.

Portable low-power thermal cycler with dual thin-film Pt heaters for a polymeric PCR chip.

Polymerase chain reaction (PCR) has been widely used for major definite diagnostic tool, but very limited its place used only indoor such as hospital or diagnosis lab. For the rapid on-site detection of pathogen in an outdoor environment, a low-power cordless polymerase chain reaction (PCR) thermal cycler is crucial module. At this point of view, we proposed a low-power PCR thermal cycler that could be operated in an outdoor anywhere. The disposable PCR chip was made of a polymeric (PI/PET) film to reduce the thermal mass. A dual arrangement of the Pt heaters, which were positioned on the top and bottom of the PCR chip, improved the temperature uniformity. The temperature sensor, which was made of the same material as the heater, utilized the temperature dependence of the Pt resistor to ensure simple fabrication of the temperature sensor. Cooling the PCR chip using dual blower fans enabled thermal cycling to operate with a lower power than that of a Peltier element with a high power consumption. The PCR components were electrically connected to a control module that could be operated with a Li-ion battery (12 V), and the PCR conditions (temperature, time, cycle, etc.) were inputted on a touch screen. For 30 PCR cycles, the accumulated power consumption of heating and cooling was 7.3 Wh, which is easily available from a compact battery. Escherichia coli genomic DNA (510 bp) was amplified using the proposed PCR thermal cycler and the disposable PCR chip. A similar DNA amplification capability was confirmed using the proposed portable and low-power thermal cycler compared with a conventional thermal cycler.

In-cell production of a genetically-encoded library based on the θ-defensin RTD-1 using a bacterial expression system.

We report the high-yield heterologous expression of bioactive θ-defensin RTD-1 inside Escherichia coli cells by making use of intracellular protein trans-splicing in combination with a high efficient split-intein. RTD-1 is a small backbone-cyclized polypeptide with three disulfide bridges and a natural inhibitor of anthrax lethal factor protease. Recombinant RTD-1 was natively folded and able to inhibit anthrax lethal factor protease. In-cell expression of RTD-1 was very efficient and yielded ≈0.7mg of folded RTD-1 per gram of wet E. coli cells. This approach was used to generate of a genetically-encoded RTD-1-based peptide library in live E. coli cells. These results clearly demonstrate the possibility of using genetically-encoded RTD-1-based peptide libraries in live E. coli cells, which is a critical first step for developing in-cell screening and directed evolution technologies using the cyclic peptide RTD-1asa molecular scaffold.

A SFTD Algorithm for Optimizing the Performance of the Readout Strategy of Residence Time Difference Fluxgate.

Residence time difference (RTD) fluxgate sensor is a potential device to measure the DC or low-frequency magnetic field in the time domain. Nevertheless, jitter noise and magnetic noise severely affect the detection result. A novel post-processing algorithm for jitter noise reduction of RTD fluxgate output strategy based on the single-frequency time difference (SFTD) method is proposed in this study to boost the performance of the RTD system. This algorithm extracts the signal that has a fixed frequency and preserves its time-domain information via a time⁻frequency transformation method. Thereby, the single-frequency signal without jitter noise, which still contains the ambient field information in its time difference, is yielded. Consequently, compared with the traditional comparator RTD method (CRTD), the stability of the RTD estimation (in other words, the signal-to-noise ratio of residence time difference) has been significantly boosted with sensitivity of 4.3 µs/nT. Furthermore, the experimental results reveal that the RTD fluxgate is comparable to harmonic fluxgate sensors, in terms of noise floor.

High-quality reference transcript datasets hold the key to transcript-specific RNA-sequencing analysis in plants.

525 I. 525 II. 526 III. 527 IV. 527 V. 529 VI. 529 529 References 529 SUMMARY: Re-programming of the transcriptome involves both transcription and alternative splicing (AS). Some genes are regulated only at the AS level with no change in expression at the gene level. AS data must be incorporated as an essential aspect of the regulation of gene expression. RNA-sequencing (RNA-seq) can deliver both transcriptional and AS information, but accurate methods to analyse the added complexity in RNA-seq data are needed. The construction of a comprehensive reference transcript dataset (RTD) for a specific plant species, variety or accession, from all available sequence data, will immediately allow more robust analysis of RNA-seq data. RTDs will continually evolve and improve, a process that will be more efficient if resources across a community are shared and pooled.