Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of cursive letters, syllables, and words handwriting in a French second-grade child with Developmental Coordination Disorder and comparison with typically developing children

Poor handwriting is a core deficit in Developmental Coordination Disorder (DCD). In a previous study, we compared the evolution of cursive letters handwriting in a girl with DCD throughout her second-grade year with that of typically developing (TD) children. We found that her handwriting evolved much less than that of TD children and remained similar to that of pre-schoolers at all stages, suggesting that her handwriting skills have reached a steady state level. We present here a continuation of this work, in which we focused on the velocity aspects of handwriting in another French child with DCD. Indeed, different velocity patterns have been observed in Chinese and English children with DCD. In the French cursive style of writing, consecutive letters are joined, a major difference with the English script style of writing. We thus analyzed the handwriting of a second-grade French girl with DCD, not only for isolated letters but also for syllables and words, in comparison to that of TD first-graders (6–7 years old; N = 85) and second-graders (7–8 years old; N = 88). Each written track was digitized, and nine kinematic parameters were measured to evaluate writing fluency. Results showed that the productions of the child with DCD were more similar to those of first-graders than to those of second-graders. In line with our previous study, the most discriminative parameters between the child with DCD and TD children were size and mean speed. Moreover, her handwriting was less fluent than that of TD children. In contrast to previous observations, we observed a higher writing velocity of the child with DCD when compared to TD children, whatever the complexity of the item, and no significant difference with TD children in the pausing time during writing. These differences may reflect linguistic specificities. For syllables and words, each letter was treated separately as a single unit, thus reflecting a problem in anticipation and automation.
Oncogenic mutations at the EGFR ectodomain structurally converge to remove a steric hindrance on a kinase-coupled cryptic epitope

Significance EGFR cancer mutations display an astonishing tissue-specific asymmetry: in lung cancer, mutations target the intracellular kinase (KD), while in glioblastomas (GBMs), a variety of missense clusters and deletions concentrate at the ectodomain (ECD). Intriguingly, GBM-activating mutations share a paradoxical preference for inhibitors that bind the inactive kinase. By integrating simulations, small-angle X-ray scattering, and GBM models, we demonstrate that ECD mutants converge to a transition state characterized by a cryptic epitope, allosterically coupled to an intermediate kinase, and synergistically blocked by antibodies and inhibitors. Our findings indicate that apparently heterogeneous aberrations remove a similar steric restrain on KD activation. The diversity of structural tricks in ECD mutants to achieve the same conformational state constitutes a potent example of molecular mimicry and convergence. Epidermal growth factor receptor (EGFR) signaling is initiated by a large ligand-favored conformational change of the extracellular domain (ECD) from a closed, self-inhibited tethered monomer, to an open untethered state, which exposes a loop required for strong dimerization and activation. In glioblastomas (GBMs), structurally heterogeneous missense and deletion mutations concentrate at the ECD for unclear reasons. We explore the conformational impact of GBM missense mutations, combining elastic network models (ENMs) with multiple molecular dynamics (MD) trajectories. Our simulations reveal that the main missense class, located at the I-II interface away from the self-inhibitory tether, can unexpectedly favor spontaneous untethering to a compact intermediate state, here validated by small-angle X-ray scattering (SAXS). Significantly, such intermediate is characterized by the rotation of a large ECD fragment (N-TR1), deleted in the most common GBM mutation, EGFRvIII, and that makes accessible a cryptic epitope characteristic of cancer cells. This observation suggested potential structural equivalence of missense and deletion ECD changes in GBMs. Corroborating this hypothesis, our FACS, in vitro, and in vivo data demonstrate that entirely different ECD variants all converge to remove N-TR1 steric hindrance from the 806-epitope, which we show is allosterically coupled to an intermediate kinase and hallmarks increased oncogenicity. Finally, the detected extraintracellular coupling allows for synergistic cotargeting of the intermediate with mAb806 and inhibitors, which is proved herein.
Stress distributions and cell flows in a growing cell aggregate

We discuss the short-time response of a multicellular spheroid to an external pressure jump. Our experiments show that 5 min after the pressure jump, the cell density increases in the centre of the spheroid but does not change appreciably close to the surface of the spheroid. This result can be explained if the cells are polarized which we show to be the case. Motivated by the experimental results, we develop a theory for polarized spheroids where the cell polarity is radial (except in a thin shell close to the spheroid surface). The theory takes into account the dependence of cell division and apoptosis rates on the local stress, the cell polarity and active stress generated by the cells and the dependence of active stress on the local pressure. We find a short-time increase of the cell density after a pressure jump that decays as a power law from the spheroid centre, which is in reasonable agreement with the experimental results. By comparing our theory to experiments, we can estimate the isotropic compression modulus of the tissue.
Hot Potatoes Heat Up BGP Routing

The separation of intradomain and interdomain routing is a key feature of the Internet routing architecture. However, intradomain routing protocols such as OSPF and IS-IS do have a (sometimes significant) influence on the path-selection process in Border Gateway Protocol (BGP). In this paper, we argue that researchers should revisit the “interface” between the two tiers of the Internet routing system. Toward this end, we present an initial analysis of the impact of OSPF on BGP in a large ISP network. We propose a general methodology for associating BGP update messages with events visible in OSPF. Then, we apply our methodology to streams of OSPF link-state advertisements and BGP update messages. Our analysis shows that (i) “hot potato” routing is sometimes a significant source of BGP updates, (ii) BGP updates can lag seconds behind the related OSPF event, which can cause delays in forwarding-plane convergence, (iii) OSPF-triggered BGP updates have a nearly uniform distribution across destination prefixes, and (iv) the fraction of BGP messages triggered by OSPF varies significantly across time and router locations, with important implications on external monitoring of BGP. Our measurement methodology and analysis results represent an important step in understanding the interplay between intradomain and interdomain routing.
The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy

KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of the dual agonist KBP-088 is unknown. We studied the effect of acute dosing with KBP-088 (5 µg/kg) and rat amylin (100, 300, and 1000 µg/kg) and subsequently compared the chronic effect of KBP-088 (5 µg/kg per day) to increasing doses of rat amylin (100, 300, and 1000 µg/kg per day) delivered by continuous subcutaneous infusion, in high-fat diet (HFD) fed Long-Evans rats. Furthermore, acute amylin sensitivity was investigated. Single dose KBP-088 (5 µg/kg) potently reduced acute food intake for a prolonged period compared with amylin (100, 300, and 1000 µg/kg), confirming the difference in potency. Independent of dose, chronic amylin administration (100, 300, and 1000 µg/kg per day) was less effective than KBP-088 (5 µg/kg per day) in inducing body weight loss (15% with KBP-088, and 5%, 9%, and 8% with amylin, vehicle corrected) and reducing overall adiposity in HFD rats. Moreover, KBP-088 improved oral glucose tolerance with significantly reduced insulin levels (80% reduction) that were better than all doses of amylin (68%, 53%, and 7% reduction). Acute amylin sensitivity was independent of the chronic treatment. Dual activation of amylin and calcitonin receptors by KBP-088 is superior to amylin in reducing body weight and improving glucose tolerance, indicating a role for the calcitonin receptor.
A USA-based registry for pulmonary arterial hypertension: 1982–2006

The aim of this study was to define the epidemiology of World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) in a large referral centre in the USA. The Pulmonary Hypertension Connection registry, initiated in 2004, evaluated all patients in a single USA practice from 1982–2006. For comparison, the authors divided the group by incident versus prevalent cohorts, aetiology and by treatment era. In total, 578 patients (77% female) aged 48±14 yrs were entered. Of these, 80% had class III or IV symptoms. Over time, connective tissue disease-associated PAH increased, while referrals for HIV remained low. One-third of patients were referred on calcium channel blocker therapy even though only 4.6% had an acute response to vasodilator challenge. When compared by treatment era, there were no differences in the severity of PAH. However, survival had improved over time, with a 1-yr survival of 85% in the incident cohort. In the USA, pulmonary arterial hypertension patients are still referred to tertiary centres too late. Referral of connective tissue disease is increasing, while referral of HIV remains low. Inappropriate calcium channel blocker treatment is common. Survival rates have increased but remain low suggesting that prognosis is improving but PAH is still a progressive, fatal disease.
Optimization of stent implantation using a high pressure inflation protocol

High‐pressure inflation is the universal standard for stent deployment but a specific protocol for its use is lacking. We developed a standardized “pressure optimization protocol” (POP) using time to inflation pressure stability as an endpoint for determining the required duration of stent inflation. Objectives: The primary study purpose was to determine the stent inflation time (IT) in a large patient cohort using the standardized inflation protocol, to correlate various patient and lesion characteristics with IT, and ascertain in an in vitro study the time for pressure accommodation within an inflation system.
A randomized controlled trial on the impact of moderate-intensity continuous aerobic exercise on the depression status of middle-aged patients with congestive heart failure

Background: Depression prevalence rates in congestive heart failure (CHF) patients have increased in the last few years. Depression is a leveled and independent risk factor for hospital readmission, decreased function, and patient mortality for patients with CHF. Major depressive disorder can be diagnosed in CHF patients who frequently suffer from sleeplessness, fatigue, and neurovegetative manifestations that extend to depressed patients. Objectives: The aim of this study was to investigate the influence of moderate-intensity continuous aerobic exercise (MICAE) on the depression status in patients with CHF. Methods: Between June and September 2017, 46 patients with CHF who suffered from depression were selected for this study. These patients aged 40 to 60 years, were medically diagnosed with CHF-related illnesses, and physical disabilities. The participating patients were selected from the psychological medicine unit of the University Hospitals. They were randomly classified into 2 groups, each group included 23 patients. The study group underwent MICAE (MICAE) 3 times weekly for 12 weeks, whereas the control group received traditional intervention without any physical exercise. Results: There were no significant differences between the 2 groups regarding baseline characteristics (P >.05). Patients in both groups had a significant decrease in their depression levels. The study group had a greater reduction of 80.9% (P <.05) when compared to a reduction in the control group 46.46% (P <.05). Conclusions: According to the study outcomes, it was concluded that 12 weeks of MICAE has positive effects on the depression status in patients with CHF. The study group who underwent moderate-intensity aerobic exercise had a greater decrease in the depression status of CHF patients when compared to the control group.
Design and Current Transporting Characteristics of 80 kV Direct Current High Temperature Superconducting Cable Core

We are now developing a high-temperature superconducting (HTS) dc cable system with the purpose of installing and operating the system on a real power grid in Cheju-island in 2013. As part of the development process, the basic design of the 250 MW HTS cable core was performed. In this paper, the key technical issues focused on the design of dc HTS cable core will be addressed and some important design results to satisfy the requirements of the power network will be presented.
Sequelae to Acromegaly: Reversibility with Treatment of the Primary Disease

Acromegalic patients suffer from a number of cardiovascular, metabolic, and rheumatologic problems, and they may also have an increased incidence of malignancy. We reviewed the literature concerning the reversibility of acromegalic complications. Hypertension, myocardial hypertrophy, left ventricular dysfunction and some rheumatologic abnormalities often continue despite successful treatment of the acromegaly. In contrast, glucose intolerance, soft tissue changes, and carpal tunnel syndrome usually resolve when the acromegaly is cured. Studies of the incidence and mortality of cancer in acromegaly are conflicting, but several suggest an increased incidence of colorectal cancer.
Differential-Evolution-Based Optimization of the Dynamic Response for Parallel Operation of Inverters With No Controller Interconnection

In this paper, the use of differential evolution (DE), a global search technique inspired by evolutionary theory, to find the parameters that are required to achieve optimum dynamic response of parallel operation of inverters with no interconnection among the controllers is proposed. Basically, in order to reach such a goal, the system is modeled in a certain way that the slopes of P- ω and Q -V curves are the parameters to be tuned. Such parameters, when properly tuned, result in system's eigenvalues located in positions that assure the system's stability and oscillation-free dynamic response with minimum settling time. This paper describes the modeling approach and provides an overview of the motivation for the optimization and a description of the DE technique. Simulation and experimental results are also presented, and they show the viability of the proposed method.
Socio-geographic variation in morphological productivity in spoken Dutch: A comparison of statistical techniques

This study explores socio-geographic variation in morphological productivity in spoken Dutch. For 72 affixes, we extracted the hapax legomena from the Corpus of Spoken Dutch. We divided the corpus into 24 subcorpora defined by the speaker’s country (Flanders versus The Netherlands), education level (High versus Non-High), sex (Women versus Men), and age (Young, Mid or Old). The large number of cells with zero counts for the affixes, and the substantial variation in the sizes of the subcorpora underlying the cell counts, posed a special challenge for the statistical analysis. We fitted three different kinds of models to our data : an ordinary least squares linear model with a transformation of the proportion of hapax legomena in the subcorpus as dependent variable, a linear mixed effects model with affix as random effect and the transformed proportions as dependent variable, and a generalized linear model with a binomial link which considered the hapax legomena as successes, and all remaining words as failures. The generalized linear model outperformed the others, in spite of the extremely small probabilities of success. We discuss why the generalized linear model is superior, and show how generalized linear models can be used to visualize by-affix variability in productivity.
From Biopower to Energopolitics in England’s Modern Waste Technology

Two energy-generating technologies in Britain which transform waste into a resource are compared. One is the (in)famous Combined Heat and Power incinerator in Sheffield, the other a forgotten biological digester in Devon utilizing anaerobic microbes. Both sites are early exemplars of experimental and biopolitical waste disposal technologies—incineration and anaerobic digestion—now regarded as leading alternatives for reducing the United Kingdom’s dependence on landfill and fossil fuel; both sites also inspired public resistance at critical moments in their development. The analysis here relates how activists and technicians struggle to demonstrate competing truths about alternative energy. Through comparison, it becomes clear that, beyond the validity of specific truth claims, energo-politics mediates the formation of technological legacies. Examining the traces energy facilities leave behind—whether in the landscape or online—we ask what it means that various claims made about some technical operations endure, while others fade into obscurity.
3.2 multi-standard 185fsrms 0.3-to-28Gb/s 40dB backplane signal conditioner with adaptive pattern-match 36-Tap DFE and data-rate-adjustment PLL in 28nm CMOS

As processing and network speeds are accelerated to support data-rich services, the bandwidth of backplane interconnects needs to be increased while maintaining the channel length and multi-rate links. However, channel losses and impedance discontinuities increase at high data-rates, making it difficult to compensate the channel. In this work, we target serial links from auto-negotiation in 100G-KR4 of 0.3Gb/s to 32GFC of 28.05Gb/s in 40dB backplane architecture. To achieve this challenge, there are two key techniques. First, we introduce a 36-tap decision-feedback equalizer (DFE) to cancel reflections due to connectors because these reflections close the eye. To operate the 36-tap DFE, we need to fix a CDR lock-point and calculate 36-tap coefficients accurately. Thus, we develop a pattern-captured CDR with a 4b pattern filter to fix the lock-point, and a 3b pattern-matched adaptive equalizer (AEQ) to optimize 36 tap coefficients. These techniques enable our chip to compensate 40dB channel loss. Second, we target 100G-KR4/40G-KR4/10G-KR/25G-KR and 32GFC/16GFC/8GFC/4GFC. To operate across a wide range of data-rates, from 0.3 to 28.05Gb/s, with low jitter, we develop a PLL architecture with two LC-VCOs and one ring VCO with a data-rate-adjustment technique by controlling an LDO. Our test chip is fabricated in 28nm CMOS. Our signal conditioner is the demonstration to achieve the BER <;1012 PRBS31 at 100G-KR4 in a 40dB chip-to-chip backplane with two connectors by using the 36-tap DFE to cancel the reflection and to operate across a wide range of data-rates from 0.3 to 28.05Gb/s.
Role of macrophages in peripheral nerve degeneration and repair

A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that the degenerating distal segment is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there.
Prevalence Study and Genetic Typing of Bovine Viral Diarrhea Virus (BVDV) in Four Bovine Species in China

To determine the nationwide status of persistent BVDV infection in different bovine species in China and compare different test methods, a total of 1379 serum samples from clinical healthy dairy cattle, beef cattle, yaks (Bos grunniens), and water buffalo (Bubalus bubalis) were collected in eight provinces of China from 2010 to 2013. The samples were analyzed using commercial antibody (Ab) and antigen (Ag) detection kits, and RT-PCR based on the 5’-UTR and Npro gene sequencing. Results showed that the overall positive rates for BVDV Ab, Ag and RT-PCR detection were 58.09% (801/1379), 1.39% (14/1010), and 22.64% (146/645), respectively, while the individual positive rates varied among regions, species, and farms. The average Ab-positive rates for dairy cattle, beef cattle, yaks, and water buffalo were 89.49% (298/333), 63.27% (248/392), 45.38% (236/520), and 14.18% (19/134), respectively, while the Ag-positive rates were 0.00% (0/116), 0.77% (3/392), 0.82% (3/368), and 5.97% (8/134), respectively, and the nucleic acid-positive rates detected by RT-PCR were 32.06% (42/131), 13.00% (26/200), 28.89% (52/180), and 19.40% (26/134), respectively. In addition, the RT-PCR products were sequenced and 124 5’-UTR sequences were obtained. Phylogenetic analysis of the 5’-UTR sequences indicated that all of the 124 BVDV-positive samples were BVDV-1 and subtyped into either BVDV-1b (33.06%), BVDV-1m (49.19%), or a new cluster, designated as BVDV-1u (17.74%). Phylogenetic analysis based on Npro sequences confirmed this novel subtype. In conclusion, this study revealed the prevalence of BVDV-1 in bovine species in China and the dominant subtypes. The high proportion of bovines with detectable viral nucleic acids in the sera, even in the presence of high Ab levels, revealed a serious threat to bovine health.
The role of the biarticular agonist and cocontracting antagonist pair in isometric muscle fatigue

Isometric knee extensions until exhaustion at 30%, 50%, and 70% of maximum voluntary contraction were performed by 18 healthy subjects. During muscle fatigue, surface electromyographic activity was recorded from the knee‐extensors vastus lateralis, vastus medialis, and rectus femoris, and the coactive antagonistic biceps femoris. The electromyographic parameter median frequency (MF) served as a measure of fatigue. Coefficients of regression of the MF fatigue changes were analyzed statistically. MF fatigue occurred within the coactive biceps femoris and was significantly more pronounced than in the quadriceps. When the MF fatigue shifts of the coactive biceps femoris were compared with each of the three investigated parts of the quadriceps separately, MF fatigue shifts were similar in shape for the biarticular coactive biceps femoris and the biarticular rectus femoris, but differed significantly between the biceps femoris and the two monoarticular muscles, vastus medialis and vastus lateralis. As both the biarticular agonist and coactive antagonist muscles fatigued at a higher rate than the two monoarticular muscles, it seems likely that this biarticular agonist/antagonist pair determines the time to the limit of endurance. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1706–1713, 1998