Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of ER‐mitochondria tethering and signalling in C9orf72‐associated amyotrophic lateral sclerosis and frontotemporal dementia

Hexanucleotide repeat expansions in C9orf72 are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mechanisms by which the expansions cause disease are not properly understood but a favoured route involves its translation into dipeptide repeat (DPR) polypeptides, some of which are neurotoxic. However, the precise targets for mutant C9orf72 and DPR toxicity are not fully clear, and damage to several neuronal functions has been described. Many of these functions are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. ER‐mitochondria signalling requires close physical contacts between the two organelles that are mediated by the VAPB‐PTPIP51 ‘tethering’ proteins. Here, we show that ER‐mitochondria signalling and the VAPB‐PTPIP51 tethers are disrupted in neurons derived from induced pluripotent stem (iPS) cells from patients carrying ALS/FTD pathogenic C9orf72 expansions and in affected neurons in mutant C9orf72 transgenic mice. In these mice, disruption of the VAPB‐PTPIP51 tethers occurs prior to disease onset suggesting that it contributes to the pathogenic process. We also show that neurotoxic DPRs disrupt the VAPB‐PTPIP51 interaction and ER‐mitochondria contacts and that this may involve activation of glycogen synthase kinases‐3β (GSK3β), a known negative regulator of VAPB‐PTPIP51 binding. Finally, we show that these DPRs disrupt delivery of Ca2+ from ER stores to mitochondria, which is a primary function of the VAPB‐PTPIP51 tethers. This delivery regulates a number of key neuronal functions that are damaged in ALS/FTD including bioenergetics, autophagy and synaptic function. Our findings reveal a new molecular target for mutant C9orf72‐mediated toxicity.
The biomechanics of turning gait in children with cerebral palsy

Turning while walking is a crucial component of locomotion; yet, little is known about how the biomechanics of turning gait differ from those of straight walking. Moreover, it is unclear how populations with restricted gait ability, such as children with cerebral palsy (CP) adapt to turning, compared to their typically developing (TD) peers. Thus, the aims of this thesis were to quantify the biomechanical differences between turning gait and straight walking in TD children and to explore if further, pathology specific, changes present during turning in children with CP. Biomechanical data, including three-dimensional body motion, ground reaction forces, and muscle activity from both groups were collected during straight walking and 90 degree turning gait using motion capture technology. Experimental data were used to compute joint kinematics (angles) and joint kinetics (moments and power) as well as more novel measures to quantify turning fluency and dynamic stability. These data were also used to derive walking simulations using a musculo-skeletal model of the human body in order to quantify muscle contributions to medio-lateral center of mass (COM) acceleration. The results show that both groups preferred to redirect their body during turning about the inside, rather than the outside, limb (with respect to the turn center). For TD children, substantial biomechanical adaptations occurred during turning, compared to straight walking. Furthermore, turning gait simulations reveal that proximal (hip abductors) and distal (ankle plantarflexors) leg muscles were mainly responsible for the redirection of the COM towards the new walking direction during turning. For children with CP, the results suggest that turning gait may be better able to reveal gait abnormalities than straight walking for a number of kinematic and kinetic gait variables. Potentially, analysis of turning gait could improve the identification and management of gait abnormalities in children with CP.
Proton Therapy in LMICs: Is the Need Justified?

Proton beam therapy (PBT), because of its unique physical and biologic properties, delivers highly conformal dose distributions compared with available conventional radiation therapy (RT) techniques. It has shown potential to minimize acute and late effects of radiation including radiation-induced second malignancies. Radiation oncologists routinely select plans on the basis of the doses to target, organs at risk, and integral dose (cumulative dose to the body). On the basis of the above, PBT plans would be chosen over the best photon plans onmost occasions. However, PBT facilities are resource-intensive to set-up andmaintain compared with even the most modern linear accelerators (linac). They require immense infrastructure and have a lower throughput compared with a linac facility. Given the higher costs and relatively limited access, it has been argued whether it is worth investing in PBT technology for an incremental improvement in dosimetry.
The Role of TQM Practice in Improving Business Performance’s Pharmaceutical Industry in Indonesia

The primary purpose of this study is to investigate the role of Total Quality Management (TQM) on business performance in various dimensions. This study proposes a conceptual model that intends to study several research hypotheses. The data were obtained through an online questionnaire, sent to pharmaceutical companies manufactured generic products in Indonesia. The study was conducted based on responses received from 168 valid questionnaires, and it was used partial least squares structural equation modeling (PLS-SEM) to test the hypotheses. Furthermore, we use both of reflective and formative construct with second order/higher order construct in our model of study which is rarely found in the previous study. This research analyzed the dimensions studied in different aspects. TQM variable consists of seven practice, namely management commitment, supplier quality, employee involvement, leadership management, customer orientation, continuous improvement and quality management system, and with respect to business performance, this variable was analyzed through four different perspectives, namely, financial, customer, internal business process and learning & growth. The findings indicate that companies adopt total quality management get improvement in their business performance. Leadership management has greater effect on the successful of TQM practice compared to other TQM dimensions. This study also provides a particular contribution for the companies and expect to be used as feedback related to the execution of their TQM implementation to improve their business performance. Keywords— Balanced Scorecard; Business Performance; Pharmaceutical Industry; Total Quality Management
Ablation of SAMD1 in Mice Causes Failure of Angiogenesis, Embryonic Lethality

Pathological retention of LDL in the intima is involved in atherosclerosis, although the retention mechanisms are not well-understood. Previously, we reported Sterile Alpha Motif Domain Containing 1 (SAMD1), a protein secreted by intimal smooth muscle cells in atherosclerotic lesions, appears to bind LDL in extracellular matrix around intimal cells. Fab-fragment inhibitors of apparently irreversible SAMD1/LDL binding reduced LDL retention in carotid injury models, but did not have a significant effect on early spontaneous lesion development. Our histology of mouse atherosclerosis models revealed extensive SAMD1 expression, possibly related to cell phenotype modulation and antigen presentation. Although the normal function of SAMD1 is unknown, it may have multiple epigenetic roles. For this report, we generated SAMD1−/−, SAMD1−/+, and SAMD1−/+ apoE−/− mice to further explore SAMD1’s role in atherosclerosis. SAMD1 was found in tissues throughout the SAMD1+/+ and SAMD1−/+ embryos. Homozygous loss of SAMD1 was embryonic lethal: at embryonic day 14, organs were partially developed and/or degraded; heads and brains were malformed; no blood vessels were observed; red blood cells were scattered and pooled, primarily near the embryo surface; and cell death was occurring. Development appeared normal in heterozygous SAMD1 embryos, but postnatal genotyping showed a reduced ability to thrive. Growth of atherosclerotic lesions in SAMD1−/+ apoE−/− after 35 weeks was not significantly less than in mice SAMD1+/+ apoE−/− mice.
Development and Validation of a Mechanistic–Empirical Design Method for Permeable Interlocking Concrete Pavement

Fully permeable (or porous or pervious) pavements are pavements whose layers are all intended to be permeable. They are used to minimize the adverse effects of stormwater runoff generated from impervious surfaces. They may also be an effective solution for cool pavement strategies for improving outdoor thermal environments and mitigating heat island effects in hot climates. Most current applications of permeable pavements in North America are used for roads with a low traffic volume, basic access streets, parking lots, and recreation and landscaped areas, all of which carry light, slow-moving traffic. Structural design methods have been empirical in nature. Mechanistic–empirical approaches for fully permeable pavement designs have not been developed, but when available, would probably speed up the implementation of fully permeable pavements and potentially extend their use to pavements with a higher volume of traffic where appropriate. This paper summarizes the development of a mechanistic–empirical design method and design tool for permeable interlocking concrete pavements, which uses mechanistic analysis and partial validation with accelerated pavement testing results. A new example design table, based on the number of days with standing water in the subbase (0, 10, 30, 50, 90, and 120), was developed with an Excel spreadsheet-based design tool. The format of the table is similar to that of the current guideline for permeable interlocking concrete pavements of the Interlocking Concrete Pavement Institute. Designs for a specific set of project circumstances can be developed with the same Excel spreadsheet-based design tool used to develop the tables along with the hydrological design procedures provided in the Interlocking Concrete Pavement Institute guide.
Solar Preheating in Power Plants: An Overview Of The Current State Of The Technology

Utilizing preheating units is one of the most critical ways to improve the performance of thermal power plants. Increasing the overall efficiency of Brayton or Rankine cycles by preheating the air or stream may result in considerable increases in output power and efficiency. When it comes to renewable energy, solar energy is an appealing alternative for use as a source of preheating since it is readily accessible. The current article discusses the use of solar energy for preheating air and steam in thermal power plants, as well as other uses. The performance of the systems is being improved, according to evaluations, as a result of a variety of elements, including the configuration of the reference system, the operating environment, the applied technology, and so on. Aside from improving the overall efficiency of the power plant, the incorporation of a solar preheating system may significantly decrease fuel usage and, as a result, carbon dioxide emissions. Furthermore, owing to the unavailability of solar energy during the night and overcast hours, thermal storage units may improve the system's dependability while also increasing the contribution of solar energy to the system's output.
Acoustic pulse reflectometry for measurement of the vocal tract and application in voice synthesis

Abstract The measurement of human airway dimensions has been a frequent objective in the fields of respiratory medicine and speech research, but has proven difficult to achieve non-invasively due to the airway's function in breathing, swallowing and speaking. Acoustic pulse reflectometry (APR) has been employed in clinical studies of the vocal tract for several years, normally in the function of airway measurement. The focus of this work is to utilise APR in capturing vocal tract profiles during the phonation of vowel sounds, for the purposes of sound synthesis. By making an equivalent tube model of the vocal tract, the propagation of an acoustic wave can be readily calculated using techniques such as waveguide modelling, which will in turn allow us to synthesise sound and form the basis of a physical model of the voice. The attractions of this technique for vocal tract measurement are many: it is non-invasive, safe, repeatable and inexpensive. In this thesis, the basic theory describing wave propagation in tubes of varying crosssection is outlined, together with a review of how the time domain technique of APR can be used to measure the input impulse response of a tubular object, such as the vocal tract, from which the bore profile can be calculated using the layer peeling algorithm. Experimental measurements of the human vocal tract during the phonation (imitation) of five non-nasalised vowels [a, e, i, o, u] are presented, using recent enhancements to the APR technique (MLS excitation signals and virtual DC tube
How Task Technology Fits with Employee Engagement, Organizational Support, and Business Outcomes: Hotel Executives’ Perspective

ABSTRACT The unpredictable external environments, constraints of internal resources, and changes in the behaviors of hotel guests create a challenge for hoteliers to initiate the latest technology advancement. This study aims to explore how hotel executives consider external criteria and employ internal resources (e.g. employee engagement and organizational support) for technology adoption decision making and planning. This work further evaluates business outcomes after technology implementation. From the extension of task–technology fit theory, a qualitative research is conducted by interviewing 14 hotel executives about technology implementation in the front office and housekeeping departments. Results indicate the influences of cost reduction, cost effectiveness, competitors, customer feedback, management strategic planning, and latest industry trends on advanced technology initiatives. The outcomes of employee engagement vary according to age, education background, and self-learning attitude. Hotel support for trainings is necessary for employee productivity enhancement. Furthermore, technology adoption benefits the financial (e.g. cost reductions of labor and maintenance) and nonfinancial outcomes (e.g. customer satisfaction and employee satisfaction) of hotels. The theoretical development and managerial implications are further discussed.
Conflict and cooperation within police units: the importance of manager inclusiveness

ABSTRACT Multisource survey data were collected from 105 police managers and 534 of their subordinates to assess the influence of manager inclusiveness on unit-level relational conflict and interpersonal helping behaviour. The analysis shows a negative relationship between relational conflict and helping behaviour and between manager inclusiveness and relational conflict. We also observe the negative link between manager inclusiveness and relational conflict is moderated by manager span of control such that the connection is weaker and not statistically significant in relatively larger units. We discuss the implications of these findings for public management research and the management of law enforcement units.
Low Load With BFR vs. High Load Without BFR Eccentric Hamstring Training Have Similar Outcomes on Muscle Adaptation

Abstract Jones, MJ, Dominguez, JF, Macatugal, C, Coleman, K, Reed, B, and Schroeder, ET. Low load with BFR vs. high load without BFR eccentric hamstring training have similar outcomes on muscle adaptation. J Strength Cond Res 37(1): 55–61, 2023—A key principle of hamstring injury rehabilitation is developing high eccentric force capability through resistance training (RT). However, it can take months before high-load RT is deemed safe and appropriate for rehabilitating serious hamstring injuries. Low-load blood flow restriction (BFR) RT has been identified as an effective alternative when high-load RT is contraindicated but has been scarcely investigated in the hamstring. To address this gap in knowledge, we sought to compare the effect of longitudinal BFR RT with traditional RT on eccentric hamstring power, strength, lean mass, perceived soreness, and acute muscle swell in healthy adults (n = 40; 19 F, 21 M; mean ± SD; age: 24.3 ± 2.6 years). Our crossover design compared the effects of low-load (30% 1RM) eccentric lower extremity training with BFR (BFR-ELET) with traditional high-load (80% 1RM) eccentric lower extremity training (TRAD-ELET) without BFR biweekly for 6 weeks. Outcomes were tested pre/post-intervention with significance at α = 0.05. Both interventions yielded dependent variable outcomes that did not differ significantly except for muscle swell assessed by bioelectrical impedance analysis, which decreased significantly more in the BFR-ELET condition compared with TRAD-ELET (mean ± SD: −0.32 ± 0.02, Φ° 50 kHz), CI: −0.35 to −0.28, Φ° 50 kHz, p < 0.001, Cohen's d = 2.95). Our findings support BFT-ELET as an effective alternative to TRAD-ELET for enhancing strength and identify myocellular swelling as a potential mediator for strength outcomes associated with BFR training.
Optimization of steam-curing regime for high-strength, self-consolidating concrete for precast, prestressed concrete applications

| PCI Journal 48 Self-consolidating concrete (SCC) can flow through densely reinforced or geometrically complex structural elements under its own weight and adequately fill the formwork with minimum segregation. Because of its high workability and high early strength, SCC is widely used in the fabrication of precast concrete elements with complex geometry. Such concrete can provide good surface finish and enhance productivity. The use of SCC opens the way for automation of concrete construction and concrete product in manufacturing processes. SCC permits the production of virtually any cross section. Sections with dense reinforcement and bottlenecks at built-in fittings can be properly cast using SCC. Fewer and smaller air bubbles form on the underside of horizontal formwork. The surface can be smoother and more uniformly colored than those with conventional vibrated concrete of normal consistency.
Fear and Attitude towards SARS-CoV-2 (COVID-19) Infection in Spanish Population during the Period of Confinement

In January 2020, the WHO classified SARS-CoV-2 infection as a public health emergency and it was declared a pandemic on 11 March 2020. The media warned about the danger of infection, fuelling the population’s fear of the new situation and increasing the perception of risk. This fear can cause behaviour that will determine the course of the pandemic and, therefore, the purpose of this study was to analyse the fear of infection from COVID-19 among the Spanish population during the state of emergency. A cross-sectional, descriptive observational study was conducted with 16,372 participants. Data on sociodemographic factors, health factors, risk perception and fear were collected through an online survey. Level of fear is associated with older age, a lower level of education, having a person infected with SARS-CoV-2 in the immediate surroundings and living with and belonging to the most socioeconomically vulnerable group of people. Risk perception is associated with increased preventive behaviour. This paper provides relevant information for the public health sector since it contributes first-hand knowledge of population data that is highly useful in terms of prevention. Understanding the experiences of people in this pandemic helps to create more effective future intervention strategies in terms of planning and management for crisis situations.
D-STATCOM predictive direct power control research under unbalanced voltage of power system

Predictive direct power control strategy is led into the research of distribution network D-STATCOM. When the grid voltage is asymmetrical, the 2 times frequency instantaneous power pulsation of PPC will cause D-STATCOM output current total harmonic distortion rate higher. After analyzing the relationship of voltage and harmonic content rate, a method is posed. In the method, the instantaneous power feedback value can be calculated through the sample positive sequence components extracted by the instantaneous symmetrical components. Then a power predictive model can be deduced according to the positive sequence equivalent circuit. The positive sequence power substituted the full power control to achieve the control of compensation current amplitude and phase. The method can eliminate the device overflow threat and ensure output current three-phase symmetry. According to the simulation and experimental results, the method is feasible and practical. Keywords—predictive direct power control; instantaneous power pulsation; harmonic total distortion rate; instantaneous symmetry components
Lightweight compositional analysis of metagenomes with FracMinHash and minimum metagenome covers

The identification of reference genomes and taxonomic labels from metagenome data underlies many microbiome studies. Here we describe two algorithms for compositional analysis of metagenome sequencing data. We first investigate the FracMinHash sketching technique, a derivative of modulo hash that supports Jaccard containment estimation between sets of different sizes. We implement FracMinHash in the sourmash software, evaluate its accuracy, and demonstrate large-scale containment searches of metagenomes using 700,000 microbial reference genomes. We next frame shotgun metagenome compositional analysis as the problem of finding a minimum collection of reference genomes that “cover” the known k-mers in a metagenome, a minimum set cover problem. We implement a greedy approximate solution using FracMinHash sketches, and evaluate its accuracy for taxonomic assignment using a CAMI community benchmark. Finally, we show that the minimum metagenome cover can be used to guide the selection of reference genomes for read mapping. sourmash is available as open source software under the BSD 3-Clause license at github.com/dib-lab/sourmash/.
Comprehensive characterisation of tribo-layer in a Cu-15Ni-8Sn alloy during dry sliding wear

The detailed characteristic of the tribo-layer in an age-hardening Cu-15Ni-8Sn alloy was studied with advanced analysis techniques. A comprehensive picture of the tribo-layer was drawn from nanoscale to macroscale. The characterisation was done for the oxide layer (OL) that is easy to scaling off during the preparation of metallographic samples, showing a homogeneous mixture of oxide and nanocrystalline particles with a thickness of several micrometers. The mechanically mixed layer (MML) is a multi-layer structure. In addition, the spinodal structure and ordered intermetallic precipitates existing in the matrix were gradually transformed or disappeared in OL and MML. Furthermore, there is a nanocrystalline transformation on the top of plastically deformed layer (PDL), where thin twin-matrix lamellar structure and equiaxed nanocrystallines were formed.