Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental design of Al2O3/MWCNT/HDPE hybrid nanocomposites for hip joint replacement

ABSTRACT Fracture in the hip joint is a major and quite common health issue, particularly for the elderly. The loads exploited by the lower limbs are very acute and severe; in the femur, they can be several folds higher than the whole weight of the body. Nanotechnology and nanocomposites offer great potential in biomedical applications. The organic materials are more biocompatible. Mechanical properties like strength and hardness are challenging parameters which control the selection of a joint. HDPE in its pure form has been successfully used as a prosthetic foot (external) but failed as an implant material due to limited mechanical properties. High-density polyethylene thermoplastic polymer (HDPE) and multi-walled carbon nanotubes (MWCNT)/Nano-Alumina is selected as a potential material for a biomedical implant and its mechanical properties and biocompatibility have been discussed. HDPE/MWCNT/Alumina (Al2O3) nanocomposites have not been explored yet for prosthetic implants. These nanocomposites were prepared in this investigation in different compositions. Prepared material has been physiochemically characterized to check the morphology and the structure. MWCNTs enhanced hardness and elastic modulus of the HDPE. Optimization of the material composition revealed that hybrid composite with structure (2.4% Al2O3 and 0.6% MWCNT) exhibits better mechanical properties compared to other ratios with 3% MWCNTs and 5% MWCNTs. Thermal gravimetric analysis (TGA) dedicates that the percentage of crystallization has been increased to 6% after adding MWCNT to HDPE. The moisture absorption decreased to 90% with 5% MWCNT. Experimental results of Colorimetric assay (MTT) of a normal human epithelial cell line (1- BJ1) over Al2O3/MWCNT@HDPE showed <20% cytotoxic activity, proving its acceptance for medical use. HDPE/MWCNT/Al2O3 nanocomposites emerged as a candidate material for artificial joints. Graphical abstract
yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development

Hypomyelination, a neurological condition characterized by decreased production of myelin sheets by glial cells, often has no known etiology. Elucidating the genetic causes of hypomyelination provides a better understanding of myelination, as well as means to diagnose, council, and treat patients. Here, we present evidence that YIPPEE LIKE 3 (YPEL3), a gene whose developmental role was previously unknown, is required for central and peripheral glial cell development. We identified a child with a constellation of clinical features including cerebral hypomyelination, abnormal peripheral nerve conduction, hypotonia, areflexia, and hypertrophic peripheral nerves. Exome and genome sequencing revealed a de novo mutation that creates a frameshift in the open reading frame of YPEL3, leading to an early stop codon. We used zebrafish as a model system to validate that YPEL3 mutations are causative of neuropathy. We found that ypel3 is expressed in the zebrafish central and peripheral nervous system. Using CRISPR/Cas9 technology, we created zebrafish mutants carrying a genomic lesion similar to that of the patient. Our analysis revealed that Ypel3 is required for development of oligodendrocyte precursor cells, timely exit of the perineurial glial precursors from the central nervous system (CNS), formation of the perineurium, and Schwann cell maturation. Consistent with these observations, zebrafish ypel3 mutants have metabolomic signatures characteristic of oligodendrocyte and Schwann cell differentiation defects, show decreased levels of Myelin basic protein in the central and peripheral nervous system, and develop defasciculated peripheral nerves. Locomotion defects were observed in adult zebrafish ypel3 mutants. These studies demonstrate that Ypel3 is a novel gene required for perineurial cell development and glial myelination.
Electrochemically Exfoliated Graphene-Like Nanosheets for Use in Ceramic Nanocomposites

In this work, the synthesis of graphene-like nanosheets (GNS) by an electrochemical exfoliation method, their microstructural characterization and their performance as fillers in a ceramic matrix composite have been assessed. To fabricate the composites, 3 mol % yttria tetragonal zirconia (3YTZP) powders with 1 vol % GNS were processed by planetary ball milling in tert-butanol to enhance the GNS distribution throughout the matrix, and densified by spark plasma sintering (SPS). According to a thorough Raman analysis and SEM observations, the electrochemically exfoliated GNS possessed less than 10 graphene layers and a lateral size lower than 1 μm. However, they contained amorphous carbon and vacancy-like defects. In contrast the GNS in the sintered composite exhibited enhanced quality with a lower number of defects, and they were wavy, semi-transparent and with very low thickness. The obtained nanocomposite was fully dense with a homogeneous distribution of GNS into the matrix. The Vickers hardness of the nanocomposite showed similar values to those of a monolithic 3YTZP ceramic sintered in the same conditions, and to the reported ones for a 3YTZP composite with the same content of commercial graphene nanosheets.
Antibody-drug conjugates (ADCs) delivering pyrrolobenzodiazepine (PBD) dimers for cancer therapy

ABSTRACT Introduction The rationally designed pyrrolobenzodiazepine (PBD) dimers emerged around ten years ago as a new class of drug component for antibody-drug conjugates (ADC). They produce highly cytotoxic DNA cross-links, exploiting a completely different cellular target to the auristatin and maytansinoid tubulin inhibitor classes and a different mode of DNA damage to other DNA interacting warheads such as calicheamicin. Areas covered The properties which make the PBD dimers suitable warheads for ADCs, and the development of the two main payload structures talirine and tesirine, are discussed. The clinical experience with the twenty PBD dimer-containing ADCs to enter the clinic is reviewed, with a focus on vadastuximab talirine and rovalpituzumab tesirine, both of which were discontinued following pivotal studies, and loncastuximab tesirine and camidanlumab tesirine which are progressing towards approval. Expert opinion Reviewing the clinical efficacy and safety data from almost forty clinical trials of PBD dimer-containing ADCs highlights the complexities and challenges of ADC early clinical development. It enables some conclusions to be made about reasons for failure and suggests strategies to optimise the future clinical development of this promising class of ADCs in a rapidly expanding field.
On the Dynamics of Wage Distributions and Unemployment Volatility

Postel-Vinay and Robin’s (2002) sequential auction model is extended to allow for aggregate productivity shocks. Workers exhibit permanent differences in ability and firms are identical. The model first predicts that negative productivity shocks may induce job destruction by driving the surplus of matches with low ability workers to negative values. Endogenous job destruction coupled with worker heterogeneity thus provides a mechanism for amplifying productivity shocks that offers an original solution to the unemployment volatility puzzle (Shimer, 2005). Second, positive or negative shocks may lead employers and employees to renegotiate low wages up and high wages down when agents’ individual surpluses become negative. The model thus delivers a rich business cycle dynamics of wage distributions that allows to explain why both low wages and high wages are more procyclical than wages in the middle of the distribution and why wage inequality may be countercyclical, as the data seem to suggest is true.
Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side

Recent clinical trials using patient’s own corrected hematopoietic stem cells (HSCs), such as for primary immunodeficiencies (Adenosine deaminase (ADA) deficiency, X-linked Severe Combined Immunodeficiency (SCID), X-linked chronic granulomatous disease (CGD), Wiskott–Aldrich Syndrome (WAS)), have yielded promising results in the clinic; endorsing gene therapy to become standard therapy for a number of diseases. However, the journey to achieve such a successful therapy is not easy, and several challenges have to be overcome. In this review, we will address several different challenges in the development of gene therapy for immune deficiencies using our own experience with Recombinase-activating gene 1 (RAG1) SCID as an example. We will discuss product development (targeting of the therapeutic cells and choice of a suitable vector and delivery method), the proof-of-concept (in vitro and in vivo efficacy, toxicology, and safety), and the final release steps to the clinic (scaling up, good manufacturing practice (GMP) procedures/protocols and regulatory hurdles).
Canonical correlation between body-posture deviations and gait disorders in children with cerebral palsy

Children with Cerebral Palsy (CP) show the postural constraints while standing, and gait disorders, resulting from both primary and secondary impairments of brain injury. In our previous studies, several characteristic postural and gait patterns in children with unilateral as well as with bilateral CP were defined, and the relationship between these patterns was demonstrated. The purpose of present study was to identify which features of body posture deviation during standing were strongly related to gait deviations in independently ambulatory children with CP. For this aim we explored the cross—relationship between features of body posture while standing examined by surface topography and the selected gait parameters from three-dimensional instrumented gait analysis in one hundred twenty children with cerebral palsy, aged between 7 and 13 years, who were able to walk independently. First, our study documented that that sagittal misalignment of the spine curvature was significantly related to kinematic deviations such as deviations of pelvic tilt, inadequate swing phase and knee flexion, and peak dorsiflexion in stance. Second, the study shows that the static asymmetry of pelvis and trunk was significantly associated with kinematic deviations during gait cycle such as pelvic rotation, hip abduction in swing, ROM of knee flexion, peak dorsiflexion in stance. Based on obtained results and referring to our previous findings it can be assumed that the first model of the relationship between postural deviation and gait disturbances, called ‘postural and gait complex of disorders in sagittal plane’, is related to children with bilateral CP, whereas the second model ‘postural and gait complex of disorders in coronal plane’ to children with unilateral CP. The clinical applications of this study relate to the early recognition of particular features of postural deviation using surface topography, instead of more difficult and demanding expensive tools 3-D gait analysis.
Physically sound, self-learning digital twins for sloshing fluids

In this paper, a novel self-learning digital twin strategy is developed for fluid sloshing phenomena. This class of problems is of utmost importance for robotic manipulation of fluids, for instance, or, in general, in simulation-assisted decision making. The proposed method infers the (linear or non-linear) constitutive behavior of the fluid from video sequences of the sloshing phenomena. Real-time prediction of the fluid response is obtained from a reduced order model (ROM) constructed by means of thermodynamics-informed data-driven learning. From these data, we aim to predict the future response of a twin fluid reacting to the movement of the real container. The constructed system is able to perform accurate forecasts of its future reactions to the movements of the containers. The system is completed with augmented reality techniques, so as to enable comparisons among the predicted result with the actual response of the same liquid and to provide the user with insightful information about the physics taking place.
AIS Electronic

Sharing economy is emerging gradually in China, which is a field worth studying, especially the use behavior of participants in e-commerce background. Based on the UTAUT model, this research considers the characteristics of sharing economy and establishes the basic framework of influencing factors of sharing behaviors. It takes P2P sharing riding as an example to do some empirical analysis through Smart PLS and SPSS PROCESS. It explores the influencing factors of participation behavior, the mediation effect of sharing intention. The study finds that performance expectancy, effort expectancy, social influence have significant positive influence on the sharing intention. The facility condition, social entertainment motivation and sustainable motivation have significant positive influence on the sharing behavior through the mediation of sharing intention
CHRONIC WASTING DISEASE MODELING: AN OVERVIEW

Abstract: Chronic wasting disease (CWD) is an infectious and fatal prion disease occurring in the family Cervidae. To update the research community regarding the status quo of CWD epidemic models, we conducted a meta-analysis on CWD research. We collected data from peer-reviewed articles published since 1980, when CWD was first diagnosed, until December 2018. We explored the analytical methods used historically to understand CWD. We used 14 standardized variables to assess overall analytical approaches of CWD research communities, data used, and the modeling methods used. We found that CWD modeling initiated in the early 2000s and has increased since then. Connectivity of the research community was heavily reliant on a cluster of CWD researchers. Studies focused primarily on regression and compartment-based models, population-level approaches, and host species of game management concern. Similarly, CWD research focused on single populations, species, and locations, neglecting modeling using community ecology and biogeographic approaches. Chronic wasting disease detection relied on classic diagnostic methods with limited sensitivity for most stages of infection. Overall, we found that past modeling efforts generated a solid baseline for understanding CWD in wildlife and increased our knowledge on infectious prion ecology. Future analytical efforts should consider more sensitive diagnostic methods to quantify uncertainty and broader scale studies to elucidate CWD transmission beyond population-level approaches. Considering that infectious prions may not follow biological rules of well-known wildlife pathogens (i.e., viruses, bacteria, fungi), assumptions used when modeling other infectious disease may not apply for CWD. Chronic wasting disease is a new challenge in wildlife epidemiology.
New Sequential Partial-Update Least Mean M-Estimate Algorithms for Robust Adaptive System Identification in Impulsive Noise

The sequential partial-update least mean square (S-LMS)-based algorithms are efficient methods for reducing the arithmetic complexity in adaptive system identification and other industrial informatics applications. They are also attractive in acoustic applications where long impulse responses are encountered. A limitation of these algorithms is their degraded performances in an impulsive noise environment. This paper proposes new robust counterparts for the S-LMS family based on M-estimation. The proposed sequential least mean M-estimate (S-LMM) family of algorithms employ nonlinearity to improve their robustness to impulsive noise. Another contribution of this paper is the presentation of a convergence performance analysis for the S-LMS/S-LMM family for Gaussian inputs and additive Gaussian or contaminated Gaussian noises. The analysis is important for engineers to understand the behaviors of these algorithms and to select appropriate parameters for practical realizations. The theoretical analyses reveal the advantages of input normalization and the M-estimation in combating impulsive noise. Computer simulations on system identification and joint active noise and acoustic echo cancellations in automobiles with double-talk are conducted to verify the theoretical results and the effectiveness of the proposed algorithms.
Quantile regression under memory constraint

This paper studies the inference problem in quantile regression (QR) for a large sample size $n$ but under a limited memory constraint, where the memory can only store a small batch of data of size $m$. A natural method is the naive divide-and-conquer approach, which splits data into batches of size $m$, computes the local QR estimator for each batch, and then aggregates the estimators via averaging. However, this method only works when $n=o(m^2)$ and is computationally expensive. This paper proposes a computationally efficient method, which only requires an initial QR estimator on a small batch of data and then successively refines the estimator via multiple rounds of aggregations. Theoretically, as long as $n$ grows polynomially in $m$, we establish the asymptotic normality for the obtained estimator and show that our estimator with only a few rounds of aggregations achieves the same efficiency as the QR estimator computed on all the data. Moreover, our result allows the case that the dimensionality $p$ goes to infinity. The proposed method can also be applied to address the QR problem under distributed computing environment (e.g., in a large-scale sensor network) or for real-time streaming data.
Mitochondrial COI Sequence Variations within and among Geographic Samples of the Hemp Pest Psylliodes attenuata from China

The hemp flea beetle Psylliodes attenuata (Coleoptera: Chrysomelidae: Psylliodes) is a common pest of Cannabis sativa, including cultivars of both industrial hemp and medicinal marijuana. Both the larval and adult stages of this beetle can cause significant damages to C. sativa, resulting in substantial crop losses. At present, little is known about the populations of this pest, including its genetic diversity. In this study, we obtained 281 P. attenuata samples from nine field sites representing broad industrial hemp productions in China and analyzed their DNA sequences at the mitochondrial COI gene, the insect DNA barcode. Our analyses revealed a total of 48 haplotypes, with 28 being found only in one specimen each while the remaining 20 were shared by two or more specimens each. Of the 20 shared haplotypes, eight were shared among local populations often from far away locations, consistent with recent long-distance dispersals. However, the observed putative long-distance dispersals have not obscured the significant genetic differentiations among the regional populations from northeastern, eastern, central and southwestern China. Interestingly, haplotype network analyses suggest evidence for potential mitochondrial recombination in natural populations of this species. We briefly discuss the implications of our results on its evolution, center of diversity, route of spread, and pest management strategies in hemp fields.
Advanced Age Increases Immunosuppression in the Brain and Decreases Immunotherapeutic Efficacy in Subjects with Glioblastoma

Purpose: Wild-type isocitrate dehydrogenase–expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% of all GBMs and has a median overall survival (OS) of <15 months. Although immune checkpoint blockade (ICB) therapy has achieved remarkable survival benefits in a variety of aggressive malignancies, similar success has yet to be achieved for GBM among phase III clinical trials to date. Our study aimed to understand the relationship between subject age and immunotherapeutic efficacy as it relates to survival from glioma. Experimental Design: (i) Clinical data: GBM patient datasets from The Cancer Genome Atlas, Northwestern Medicine Enterprise Data Warehouse, and clinical studies evaluating ICB were stratified by age and compared for OS. (ii) Animal models: young, middle-aged, and older adult wild-type and indoleamine 2,3 dioxygenase (IDO)-knockout syngeneic mice were intracranially engrafted with CT-2A or GL261 glioma cell lines and treated with or without CTLA-4/PD-L1 mAbs, or radiation, anti–PD-1 mAb, and/or a pharmacologic IDO enzyme inhibitor. Results: Advanced age was associated with decreased GBM patient survival regardless of treatment with ICB. The advanced age–associated increase of brain IDO expression was linked to the suppression of immunotherapeutic efficacy and was not reversed by IDO enzyme inhibitor treatment. Conclusions: Immunosuppression increases in the brain during advanced age and inhibits antiglioma immunity in older adults. Going forward, it will be important to fully understand the factors and mechanisms in the elderly brain that contribute to the decreased survival of older patients with GBM during treatment with ICB.
Pembrolizumab in relapsed or refractory Richter syndrome

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