Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers for drug development in propionic and methylmalonic acidemias

There is an unmet need for the development and validation of biomarkers and surrogate endpoints for clinical trials in propionic acidemia (PA) and methylmalonic acidemia (MMA). This review examines the pathophysiology and clinical consequences of PA and MMA that could form the basis for potential biomarkers and surrogate endpoints. Changes in primary metabolites such as methylcitric acid (MCA), MCA:citric acid ratio, oxidation of 13C‐propionate (exhaled 13CO2), and propionylcarnitine (C3) have demonstrated clinical relevance in patients with PA or MMA. Methylmalonic acid, another primary metabolite, is a potential biomarker, but only in patients with MMA. Other potential biomarkers in patients with either PA and MMA include secondary metabolites, such as ammonium, or the mitochondrial disease marker, fibroblast growth factor 21. Additional research is needed to validate these biomarkers as surrogate endpoints, and to determine whether other metabolites or markers of organ damage could also be useful biomarkers for clinical trials of investigational drug treatments in patients with PA or MMA. This review examines the evidence supporting a variety of possible biomarkers for drug development in propionic and methylmalonic acidemias.
Introduction: The Iron Law of Megaproject Management

Megaprojects are large, they are constantly growing ever larger, and more and more are being built in what has been called the biggest investment boom in history. This chapter serves as an introduction to megaprojects, and to The Oxford Handbook of Megaproject Management. First, megaprojects are defined and the size of the global megaprojects business is estimated. Second, drivers of the megaproject boom are identified, including monumentalism and the technological sublime. Third, ten things you must know about megaprojects are detailed, from their tendency to suffer from uniqueness bias to their overexposure to black-swan events. Fourth, the "iron law of megaprojects" is identified as a main challenge to megaproject management: "Over budget, over time, under benefits, over and over again. " Finally, the main structure of the Handbook is set out as covering the what, the why, and the how of megaproject management, in terms of the challenges, causes, and cures that students of megaprojects must decipher to better understand and better manage megaprojects.
Drosophila ZIP13 over‐expression or transferrin1 RNAi influences the muscle degeneration of Pink1 RNAi by elevating iron levels in mitochondria

Disruption of iron homeostasis in the brain of Parkinson's disease (PD) patients has been reported for many years, but the underlying mechanisms remain unclear. To investigate iron metabolism genes related to PTEN‐induced kinase 1 (Pink1) and parkin (E3 ubiquitin ligase), two PD‐associated proteins that function to coordinate mitochondrial turnover via induction of selective mitophagy, we conducted a genetic screen in Drosophila and found that altered expression of genes involved in iron metabolism, such as Drosophila ZIP13 (dZIP13) or transferrin1 (Tsf1), significantly influences the disease progression related to Pink1 but not parkin. Several phenotypes of Pink1 mutant and Pink1 RNAi but not parkin mutant were significantly rescued by over‐expression (OE) of dZIP13 (dZIP13 OE) or silencing of Tsf1 (Tsf1 RNAi) in the flight muscles. The rescue effects of dZIP13 OE or Tsf1 RNAi were not exerted through mitochondrial disruption or mitophagy; instead, the iron levels in mitochondira were significantly increased, resulting in enhanced activities of enzymes participating in respiration and increased ATP synthesis. Consistently, the rescue effects of dZIP13 OE or Tsf1 RNAi on Pink1 RNAi can be inhibited by decreasing the iron levels in mitochondria through mitoferrin (dmfrn) RNAi. This study suggests that dZIP13, Tsf1, and dmfrn might act independently of parkin in a parallel pathway downstream of Pink1 by modulating respiration and indicates that manipulation of iron levels in mitochondria may provide a novel therapeutic strategy for PD associated with Pink1.
Distributed Convex Optimal Power Flow Model Based on Alternating Direction Method of Multipliers For Power Distribution System

The objective of OPF is to find an operating point for a network minimizing certain cost functions such as line losses or generation costs. In recent years, a significant rise in distributed generation (DG) penetration in the distribution network made the OPF problem a greater computational burden. As a result, the centralized OPF formulation is facing more challenges. In this paper a fully distributed approach has been proposed that utilizes the convergence proper of alternating direction method of multipliers (ADMM) and split the central OPF problem into small problems of regions. All the regional OPF problems are parallelizable and computationally cheaper than the centralized approach. The non-linear, non-convex AC-OPF problem in this approach uses SDP relaxation to convexify. The proposed approach is tested on the modified IEEE 123 bus system to prove it’s scalability.
A Privacy-Preserving Distributed Analytics Platform for Health Care Data

Background In recent years, data-driven medicine has gained increasing importance in terms of diagnosis, treatment, and research due to the exponential growth of health care data. However, data protection regulations prohibit data centralisation for analysis purposes because of potential privacy risks like the accidental disclosure of data to third parties. Therefore, alternative data usage policies, which comply with present privacy guidelines, are of particular interest. Objective We aim to enable analyses on sensitive patient data by simultaneously complying with local data protection regulations using an approach called the Personal Health Train (PHT), which is a paradigm that utilises distributed analytics (DA) methods. The main principle of the PHT is that the analytical task is brought to the data provider and the data instances remain in their original location. Methods In this work, we present our implementation of the PHT paradigm, which preserves the sovereignty and autonomy of the data providers and operates with a limited number of communication channels. We further conduct a DA use case on data stored in three different and distributed data providers. Results We show that our infrastructure enables the training of data models based on distributed data sources. Conclusion Our work presents the capabilities of DA infrastructures in the health care sector, which lower the regulatory obstacles of sharing patient data. We further demonstrate its ability to fuel medical science by making distributed data sets available for scientists or health care practitioners.
Comparing Three Aerodynamic Models for Predicting the Thrust and Power Characteristics of a Yawed Floating Wind Turbine Rotor

This study compares the time-varying rotor thrust and shaft power characteristics of a yawed floating offshore wind turbine (FOWT) predicted by three different open-source aerodynamic models. These models involve the blade-element-momentum (BEM) and the general dynamic wake (GDW) methods implemented in the design code fast developed by NREL, and a higher fidelity free-wake vortex model (FWVM) that is capable of modeling the unsteady skewed helical wake development of the yawed rotor. The study is based on the NREL 5 MW baseline rotor installed on the MIT tension-leg platform (TLP) operating with different rotor yaw angles and under regular sea wave conditions. Both the undisturbed wind speed and rotor speed are maintained constant throughout the analysis, though different sea wave heights and periods are considered. Initially, the motions of the FOWT under both axial and yawed rotor conditions are estimated in a time domain using fast. These motions are then prescribed to winds, an open-source FWVM developed by the University of Massachusetts Amherst, to determine the aerodynamic rotor thrust and power as a function of time. Both TLP surge and pitch motions are noted to impact the rotor thrust and power characteristics considerably. The three models have consistently shown that the TLP motion exhibits a negligible impact on the time-averaged rotor shaft thrust and power of the yawed rotor. On the other hand, the cyclic component of rotor thrust and power are found to be significantly influenced by the wave state at all yaw angles. Significant discrepancies between the predictions for this cyclic component from the three models are observed, suggesting the need of further research through experimental validation to ensure more reliable aerodynamics models are developed for floating wind turbine design software packages.
Predicting Venous Thrombosis in Osteoarthritis Using a Machine Learning Algorithm: A Population-Based Cohort Study

Osteoarthritis (OA) is the most common joint disease associated with pain and disability. OA patients are at a high risk for venous thrombosis (VTE). Here, we developed an interpretable machine learning (ML)-based model to predict VTE risk in patients with OA. To establish a prediction model, we used six ML algorithms, of which 35 variables were employed. Recursive feature elimination (RFE) was used to screen the most related clinical variables associated with VTE. SHapley additive exPlanations (SHAP) were applied to interpret the ML mode and determine the importance of the selected features. Overall, 3169 patients with OA (average age: 66.52 ± 7.28 years) were recruited from Xi’an Honghui Hospital. Of these, 352 and 2817 patients were diagnosed with and without VTE, respectively. The XGBoost algorithm showed the best performance. According to the RFE algorithms, 15 variables were retained for further modeling with the XGBoost algorithm. The top three predictors were Kellgren–Lawrence grade, age, and hypertension. Our study showed that the XGBoost model with 15 variables has a high potential to predict VTE risk in patients with OA.
Micro-electro-thermo-magnetic Actuators for MEMS Applications

This research focuses on developing new techniques and designs for highly controllable microactuating systems with large force-stroke outputs. A fixed-fixed microbeam is the actuating element in the introduced techniques. Either buckling of a microbridge by thermal stress, lateral deflection of a microbridge by electromagnetic force, or combined effects of both can be employed for microactuation. The proposed method here is MicroElectroThermoMagnetic Actuation (METMA), which uses the combined techniques of electrical or electro-thermal driving of a microbridge in the presence of a magnetic field. The electrically controllable magnetic field actuates and controls the electrically or electrothermally driven microstructures. METMA provides control with two electrical inputs, the currents driving the microbridge and the current driving the external magnetic field. This method enables a more controllable actuating system. Different designs of microactuators have been implemented by using MEMS Pro as the design software and MUMPs as the standard MEMS fabrication technology. In these designs, a variety of out-ofplane buckling or displacement of fixed-fixed microbeams have been developed and employed as the actuating elements. This paper also introduces a novel actuating technique for larger displacements that uses a two-layer buckling microbridge actuated by METMA. Heat transfer principles are applied to investigate temperature distribution in a microbeam, electrothermal heating, and the resulting thermoelastic effects. Furthermore, a method for driving microactuators by applying powerful electrical pulses is proposed. The integrated electromagnetic and electrothermal microactuation technique is also studied. A clamped-clamped microbeam carrying electrical current has been modeled and simulated in ANSYS. The simulations include electrothermal, thermoelastic, electromagnetic, and electrothermomagnetic effects. The contributions are highlighted, the results are discussed, the research and design limitations are reported, and future works are proposed.
A low power digital baseband core for wireless micro-neural-interface using CMOS sub/near-threshold circuit

This thesis presents the work on designing and implementing a low power digital baseband core with custom-tailored protocol for wirelessly powered MicroNeural-Interface (MNI) System-on-Chip (SoC) to be implanted within the skull to record cortical neural activities. The core, on the tag end of distributed sensors, is designed to control the operation of individual MNI and communicate and control MNI devices implanted across the brain using received downlink commands from external base station and store/dump targeted neural data uplink in an energy efficient manner. The application specific protocol defines three modes (Time Stamp Mode, Streaming Mode and Snippet Mode) to extract neural signals with on-chip signal conditioning and discrimination. In Time Stamp Mode, Streaming Mode and Snippet Mode, the core executes basic on-chip spike discrimination and compression, real-time monitoring and segment capturing of neural signals so single spike timing as well as inter-spike timing can be retrieved with high temporal and spatial resolution. To implement the core control logic using sub/nearthreshold logic, a novel digital design methodology is proposed which considers INWE (Inverse-Narrow-Width-Effect), RSCE (Reverse-Short-Channel-Effect) and variation comprehensively to size the transistor width and length accordingly to achieve close-tooptimum digital circuits. Ultra-low-power cell library containing 67 cells including physical cells and decoupling capacitor cells using the optimum fingers is designed, laidout, characterized, and abstracted. A robust on-chip sense-amp-less SRAM memory (8X32 size) for storing neural data is implemented using 8T topology and LVT fingers. The design is validated with silicon tapeout and measurement shows the digital baseband core works at 400mV and 1.28 MHz system clock with an average power consumption of 2.2 μW, resulting in highest reported communication power efficiency of 290Kbps/μW to date.
Anomaly Detection in Maritime AIS Tracks: A Review of Recent Approaches

The automatic identification system (AIS) was introduced in the maritime domain to increase the safety of sea traffic. AIS messages are transmitted as broadcasts to nearby ships and contain, among others, information about the identification, position, speed, and course of the sending vessels. AIS can thus serve as a tool to avoid collisions and increase onboard situational awareness. In recent years, AIS has been utilized in more and more applications since it enables worldwide surveillance of virtually any larger vessel and has the potential to greatly support vessel traffic services and collision risk assessment. Anomalies in AIS tracks can indicate events that are relevant in terms of safety and also security. With a plethora of accessible AIS data nowadays, there is a growing need for the automatic detection of anomalous AIS data. In this paper, we survey 44 research articles on anomaly detection of maritime AIS tracks. We identify the tackled AIS anomaly types, assess their potential use cases, and closely examine the landscape of recent AIS anomaly research as well as their limitations.
Experimentation Environments for Data Center Routing Protocols: A Comprehensive Review

The Internet architecture has been undergoing a significant refactoring, where the past preeminence of transit providers has been replaced by content providers, which have a ubiquitous presence throughout the world, seeking to improve the user experience, bringing content closer to its final recipients. This restructuring is materialized in the emergence of Massive Scale Data Centers (MSDC) worldwide, which allows the implementation of the Cloud Computing concept. MSDC usually deploy Fat-Tree topologies, with constant bisection bandwidth among servers and multi-path routing. To take full advantage of such characteristics, specific routing protocols are needed. Multi-path routing also calls for revision of transport protocols and forwarding policies, also affected by specific MSDC applications’ traffic characteristics. Experimenting over these infrastructures is prohibitively expensive, and therefore, scalable and realistic experimentation environments are needed to research and test solutions for MSDC. In this paper, we review several environments, both single-host and distributed, which permit analyzing the pros and cons of different solutions.
Phytochemical Studies on Two Unexplored Endemic Medicinal Plants of India, Barleria terminalis and Calacanthus grandiflorus

Barleria terminalis Nees and Calacanthus grandiflorus (Dalzell) Radlk. are endemic medicinal plants of the Western Ghats of India. The aim of the present research work was to investigate phytochemical profile, potent bioactives using RP-HPLC, LC-MS and GC-MS and to evaluate their bioactivities. Acetone was found to be the best extraction medium for separating phytochemicals. Similarly, acetone and methanol extracts exhibited potential antioxidant properties. Ethanol extract of B. terminalis stem showed potent acetylcholinesterase (AChE) (89.10 ± 0.26%) inhibitory activity. Inhibition of α-amylase (36.96 ± 2.96%) activity was observed the best in ethanol extract of B. terminalis leaves and α-glucosidase inhibitory activity (94.33 ± 0.73%) in ethanol extract of C. grandiflorus stem. RP-HPLC analysis confirmed the presence of several phenolic compounds (gallic acid, hydroxybenzoic acid, vanillic acid, chlorogenic acid and coumaric acid) and phenylethanoid glycoside (verbascoside). The highest phenolics content were observed in B. terminalis (GA (4.17 ± 0.002), HBA (3.88 ± 0.001), VA (4.54 ± 0.001), CHLA (0.55 ± 0.004) mg/g DW, respectively). Similarly, LC-MS and GC-MS revealed the presence of phenolics, glycosides, terpenes, steroids, fatty acids, etc. Moreover, positive correlation between studied phytochemicals and antioxidants was observed in principal component analysis. Based on the present investigation, we conclude that B. terminalis and C. grandiflorus can be further explored for their active principles particularly, phenylethanoid glycosides and iridoids and their use in drug industry for pharmaceutical purposes.
An investigation into the effect of unilateral immobilisation of the upper limb on the physiological responses to stair climbing

Introduction: Musculoskeletal conditions or injuries to the shoulder are frequently seen within primary healthcare practice, with a number of these complaints resulting in restricted joint mobility. It is known that minor restrictions to movement, particularly those that disrupt the normal gait cycle, result in an increased energy demand. Though previous studies have not demonstrated any increase in energy demand during a level walking task with an immobilised upper limb, the extent to which upper limb immobilisation during stair climbing has on physiological outcomes has yet to be determined. Purpose: The objective of this study was to measure the effect of unilateral restriction of upper limb on energetic cost of stair climbing. Methods: Thirty four participants, 16 males (age 28 ± 9 years, height 181 ± 6cm, weight 75 ± 13kg) and 18 females (age 23 ± 4 years, height 170 ± 5cm, weight 64 ± 6kg) ascended a public access staircase at a rate of 80 steps.min -1 for five minutes and fifteen seconds over two experimental trials. Participants were randomly assigned to conduct the trial with complete mobility, followed by immobilisation of the dominant (n=17) or non-dominant (n=17) upper extremity, or vice versa. Outcome measures of oxygen uptake (mL.kg -1 .min -1 ), total energy cost (kcal.d -1 ), relative energy expenditure (kcal.d -1 .kg -1 ) and heart rate (beats.min -1 ) were recorded and utilised in data analysis, relating to pre(0 minutes 0 seconds) versus post(5 minutes 15 seconds) the experimental time both within and between the groups (immobilised and nonimmobilised). Results: Post stair climb data shows only a trivial to small difference in the physiological measures of the non-immobilised and immobilised groups (oxygen uptake; 1.4 ± 0.5 and 1.4 ± 0.4mL.min -1 .kg -1 , heart rate; 58 ± 16 and 59 ± 16beats.min -1 , total energy cost; 9858 ± 3560 and 10499 ± 3062kcal.d -1 , and relative energy expenditure 139 ± 42 and 149 ± 39kcal.d -1 .kg -1 , respectively). A trivial to small difference in the physiological measures in the two groups prior to the stair climb task (oxygen uptake; 0.5 ± 0.2 and 0.5 ± 0.2mL.min -1 .kg -1 , heart rate; 103 ± 19 and 106 ± 14beats.min -1 , total energy cost; 3711 ± 1555 and 3362 ± 1419kcal.d -1 , and relative energy expenditure 53 ± 23 and 48 ± 21kcal.d -1 .kg -1, , respectively) and a large difference preto postthe stair climbing task in the outcome measures was observed. Additional analysis demonstrates only a trivial to small difference in the physiological measures between order of immobilisation, and between immobilisation of the dominant or non-dominant upper limb. Conclusion: Immobilisation of the upper limb had only a trivial to small effect on oxygen uptake, heart rate, total energy cost, and relative energy expenditure during a stair climbing task.
Definition and utilization of a series of parameters to evaluate an e-business idea

In this paper we will present an innovative set of parameters that aim to contribute in the evaluation of the soundness and effectiveness of a new e-business idea during the selection phase. We will present a method that integrates the traditional business analysis concepts through the identification of new effectiveness measures that are specific to the e-business. The parameters identified, named "conceptual accessibility" and "technological accessibility" have been tuned through a reference panel of potential users and measured on a enterprise reference group of well known e-business ventures to assess the soundness of the identified parameters. For each of these parameters we will present a definition and a metric that will allow a quantitative evaluation of the idea with respect to each of them.
Insect galls on Asteraceae in Brazil: richness, geographic distribution, associated fauna, endemism and economic importance

Abstract: An overview of insect galls on Asteraceae in Brazil is presented. We used the Web of Science database to find publications about insect galls from 1988 to 2020. We analyzed 88 publications and collected data from 51 of those. A total of 487 gall morphotypes were counted on 157 plant species of 42 genera. This value singled out Asteraceae as the richest plant family in number of gall morphotypes in Brazil. Most morphotypes were recorded in the Atlantic Forest (41%) and Cerrado (30.5%), the most surveyed biomes in Brazil. Baccharis L. supported the greatest gall richness (43.9%), which could be explained by the hypotheses of geographic area and taxon size. Baccharis concinna G.M. Barroso, B. dracunculifolia DC. and B. platypoda DC. were indicated as superhost species. Most galls were induced on stems (52.2%), a pattern known in Asteraceae for gall-inducing Tephritidae and Chloropidae, and extended in the present study to Cecidomyiidae. Most galls were fusiform (42.5%), which can be related to the highest number of gall on stems. Cecidomyiidae (Diptera) were the most frequent inducers, as observed worldwide. The presence of other dwellers - parasitoids, cecidophages, kleptoparasites, and successors - were reported in 8.8% of the gall morphotypes, being parasitoids the most frequent, as found in other Brazilian publications. Most host plants (58%) are endemic to Brazil, 14% are useful and few are vulnerable or endangered (six and four species, respectively). Due to the high host specificity, the gall-inducers associated with these plants can also be considered either endemic, important, vulnerable and/or endangered, respectively.