Miracle-dz/UniFAR-FTUs huggingface dataset:
Soluble tau aggregates, not large fibrils, are the toxic species that display seeding and cross‐seeding behavior

Several studies have proposed that fibrillary aggregates of tau and other amyloidogenic proteins are neurotoxic and result in numerous neurodegenerative diseases. However, these studies usually involve sonication or extrusion through needles before experimentation. As a consequence, these methods may fragment large aggregates producing a mixture of aggregated species rather than intact fibrils. Therefore, the results of these experiments may be reflective of other amyloidogenic species, such as oligomers and/or protofibrils/short fibrils. To investigate the effects of sonication on the aggregation of tau and other amyloidogenic proteins, fibrils were prepared and well characterized, then sonicated and evaluated by various biochemical and biophysical methods to identify the aggregated species present. We found that indeed a mixture of aggregated species was present along with short fibrils indicating that sonication leads to impure fibril samples and should be analyzed with caution. Our results corroborate the previous studies showing that sonication of prion and Aβ fibrils leads to the formation of toxic, soluble aggregates. We also show that the oligomeric forms are the most toxic species although it is unclear how sonication causes oligomer formation. Recent results suggest that these small toxic oligomers produced by sonication, rather than the stable fibrillar structures, are prion‐like in nature displaying seeding and cross‐seeding behavior.
Histopathology of Bordetella pertussis in the Baboon Model

Pertussis is a severe respiratory disease caused by Bordetella pertussis. The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. ABSTRACT Pertussis is a severe respiratory disease caused by Bordetella pertussis. The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases. The baboon model of pertussis provides the opportunity to evaluate the histopathology of severe but nonfatal pertussis. The baboon model recapitulates the characteristic clinical signs of pertussis observed in humans, including leukocytosis, paroxysmal coughing, mucus production, heavy colonization of the airway, and transmission of the bacteria between hosts. As in humans, baboons demonstrate age-related differences in clinical presentation, with younger animals experiencing more severe disease. We examined the histopathology of 5- to 6-week-old baboons, with the findings being similar to those reported for fatal human infant cases. In juvenile baboons, we found that the disease is highly inflammatory and concentrated to the lungs with signs of disease that would typically be diagnosed as acute respiratory distress syndrome (ARDS) and bronchopneumonia. In contrast, no significant pathology was observed in the trachea. Histopathological changes in the trachea were limited to cellular infiltrates and mucus production. Immunohistostaining revealed that the bacteria were localized to the surface of the ciliated epithelium in the conducting airways. Our observations provide important insights into the pathology of pertussis in typical, severe but nonfatal pertussis cases in a very relevant animal model.
Drift and Its Mediation in Terrestrial Orbits

The slow deformation of terrestrial orbits in the medium range, subject to lunisolar resonances, is well approximated by a family of Hamiltonian flow with $2.5$ degree-of-freedom. The action variables of the system may experience chaotic variations and large drift that we may quantify. Using variational chaos indicators, we compute high-resolution portraits of the action space. Such refined meshes allow to reveal the existence of tori and structures filling chaotic regions. Our elaborate computations allow us to isolate precise initial conditions near specific zones of interest and study their asymptotic behaviour in time. Borrowing classical techniques of phase- space visualisation, we highlight how the drift is mediated by the complement of the numerically detected KAM tori.
Tangent-Normal Adversarial Regularization for Semi-Supervised Learning

Compared with standard supervised learning, the key difficulty in semi-supervised learning is how to make full use of the unlabeled data. A recently proposed method, virtual adversarial training (VAT), smartly performs adversarial training without label information to impose a local smoothness on the classifier, which is especially beneficial to semi-supervised learning. In this work, we propose tangent-normal adversarial regularization (TNAR) as an extension of VAT by taking the data manifold into consideration. The proposed TNAR is composed by two complementary parts, the tangent adversarial regularization (TAR) and the normal adversarial regularization (NAR). In TAR, VAT is applied along the tangent space of the data manifold, aiming to enforce local invariance of the classifier on the manifold, while in NAR, VAT is performed on the normal space orthogonal to the tangent space, intending to impose robustness on the classifier against the noise causing the observed data deviating from the underlying data manifold. Demonstrated by experiments on both artificial and practical datasets, our proposed TAR and NAR complement with each other, and jointly outperforms other state-of-the-art methods for semi-supervised learning.
STEAP1 Regulates Tumorigenesis and Chemoresistance During Peritoneal Metastasis of Gastric Cancer

In China, majority of the mortality in gastric cancer are associated with peritoneal metastasis. Since most gastric tumors are metastatic at initial diagnosis, the treatment of gastric cancer is limited to radical resection. Therefore, it is imperative to identify diagnostic and prognostic biomarkers. From 2014 to 2015, 20 patients were enrolled in the study. To search translationally upregulated genes in the context of epithelial to mesenchymal transition (EMT), polysome profiling was performed. The MTT, migration, and invasion assay were conducted to determine cell proliferation, migration, and invasion ability respectively. Experiments of gain and loss of function were performed using the overexpression plasmid, siRNA, and shRNA. Xenograft assay was established using nude mice to explore the role of targets translationally upregulated gene in vivo. Polysome profiling defined the landscape of translationally regulated gene products with differential expression between non-metastatic and metastatic cohorts. Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) was found to be the most translationally upregulated gene product in either experimental groups. STEAP1 was found to be required for cell proliferation, in vitro migration and invasion, and in vivo tumorigenesis. RNAi-mediated silencing of STEAP1 potentiated chemosensitivity of the MKN45 cells to docetaxel treatment, highlighting the importance of STEAP1 as a novel biomarker in gastric cancer patients with peritoneal metastasis. STEAP1 is thus induced translationally and its expression promotes proliferation, migration, invasiveness, and tumorigenicity of gastric cancer. STEAP1 can be a potent candidate for designing of targeted therapy.
Current Progress in CNS Imaging of Myotonic Dystrophy

Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first revealed hyperintense white matter lesions, predominantly localized in the anterior temporal lobe. Brain atrophy and ventricle enlargement were additional early findings already described almost 30 years ago. Since then, more advanced and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1 and 2. Involvement of actually normal appearing white matter and widespread cortical affection in PET studies were key results toward the recognition of diffuse and not only focally localized brain pathology in vivo. Later, structural abnormalities of both, gray and white matter, have been found in both forms of the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a consistent widespread cortical and subcortical involvement of gray and white matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy studies gave additional evidence of neuronal and glial damage in both types. Central questions regarding the origin and spatiotemporal evolution of the CNS involvement and its relevance for clinical symptoms had already been raised 30 years ago, however are still not answered. Results of correlation analyses between neuroimaging and clinical parameters are diverse and with few exceptions not well reproducible across studies. It may be related to the fact that most of the reported studies included only small numbers of subjects, sometimes even not separating Myotonic Dystrophy Type 1 from Type 2. But this heterogeneity may also support the current point of view that the clinical impairments are not simply linked to specific and regionally circumscribed structural or functional brain alterations. It seems more convincing that disturbed networks build the functional and structural substrate of clinical symptoms in these disorders as it is proposed in other neuropsychiatric diseases. Consecutively, structural and functional network analyses may provide additional information regarding the link between brain pathology and clinical symptoms. Up to now, only cross-sectional neuroimaging studies have been published. To analyze the temporal evolution of brain affection, longitudinal studies are urgently needed, and systematic natural history data would be useful to identify potential biomarkers for therapeutic studies.
Role of nuclear factor κB in multiple sclerosis and experimental autoimmune encephalomyelitis

The transcription factor nuclear factor κB (NF-κB) plays major roles in inflammatory diseases through regulation of inflammation and cell viability. Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). It has been shown that NF-κB is activated in multiple cell types in the CNS of MS patients, including T cells, microglia/macrophages, astrocytes, oligodendrocytes, and neurons. Interestingly, data from animal model studies, particularly studies of experimental autoimmune encephalomyelitis, have suggested that NF-κB activation in these individual cell types has distinct effects on the development of MS. In this review, we will cover the current literature on NF-κB and the evidence for its role in the development of MS and its animal model experimental autoimmune encephalomyelitis.
Factors affecting patient and nursing staff adherence to an integrated physical activity and nutritional intervention targeting functional decline on an acute medical ward: a qualitative study

Background Medical patients are particularly at risk of developing complications during and after hospitalization, due to impaired nutritional intake, physical inactivity, or immobilization. Evaluations of implementation studies on health-promoting interventions for medical patients in hospitals are scarce. The aim of this study was to identify factors affecting the adherence of patients and staff to an integrated physical activity and nutritional intervention on a medical ward. Methods Two focus group interviews were conducted: one with patients and another with staff. Three individual telephone interviews were conducted, as three patients were not available at the time of the group interview. An inductive thematic analysis was fundamental to the findings of the study. Findings Nine themes describe factors affecting adherence to integrated physical activity and nutrition intervention. Positive factors described by the patients were new knowledge and insight, and that they felt seen and believed in, which made a significant difference to their motivation. The nursing staff felt that the intervention provided important knowledge related to daily practice, prevented bad consciences due to time issues, and that they experienced happier and more active patients. Both staff and patients found that the approaches of the physiotherapist and the dietician positively changed their behavior, however staff members experienced limited resources as a barrier, and a lack of knowledge seemed to hinder full integration of the intervention. Patients reported that their illness situation, “being on their own,” and failure to negotiate a shared goal with the project staff were barriers to adherence. Conclusions Both the nursing staff and patients described positive experiences with the integration of a multifaceted health promotion intervention on physical activity and nutrition, however the nursing staff did not fully participate in the intervention and patient adherence differed; particularly, it tended to diminish when the patients were expected to act on their own.
Species-Associated Differences in the Below-Ground Microbiomes of Wild and Domesticated Setaria

The rhizosphere microbiome is known to play a crucial role in promoting plant growth, partly by countering soil-borne phytoparasites and by improving nutrient uptake. The abundance and composition of the rhizosphere and root-associated microbiota are influenced by several factors, including plant species and genotype. We hypothesize that crop domestication might influence the composition and diversity of plant-associated microbiomes. We tested the contribution of domestication to the bacterial and archaeal root and soil composition associated with six genotypes of domesticated Setaria italica and four genotypes of its wild ancestor, S. viridis. The bacterial microbiome in the rhizoplane and root endophyte compartments, and the archaea in the endophyte compartment, showed major composition differences. For instance, members of the Betaproteobacteria and Firmicutes were overrepresented in S. italica root samples compared to S. viridis. Metagenomic analysis of samples that contained both root surface-bound (rhizoplane) and inside-root (endophytic) bacteria defined two unique microbial communities only associated with S. italica roots and one only associated with S. viridis roots. Root endophytic bacteria were found in six discernible communities, of which four were primarily on S. italica and two primarily on S. viridis. Among archaea, Methanobacteria, and Methanomicrobia exhibited species-associated differences in the rhizosphere and root compartments, but most detected archaea were not classified more specifically than at the level of phylum. These results indicate a host genetic contribution to the microbial composition in Setaria, and suggest that domestication has selected for specific associations in the root and in the rhizosphere.
Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA

Purpose To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms. Methods The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells. Results The relative mRNA levels of ERRa in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) (P<0.05), and similar results were observed for ERRα protein levels. A higher ratio of ERa/ERRa was observed in ERα-positive RL-952 (10-fold) and ANC-3A (8.5-fold) cells, whereas a lower ratio was observed in ERα-negative HEC-1A (3.75-fold) and HEC-1B cells (0-fold). Both – exogenous XCT790 and endogenous siRNA-ERRα – can decrease the expression of ERRα, thereby inhibiting proliferation but promoting apoptosis in both ERα-positive and -negative EC cells. The XCT790 presented higher proliferation-inhibition and apoptosis rates in the ERα-positive than ERα-negative cells, whereas the siRNA-ERRα exhibited higher proliferation-inhibition and apoptosis rates in the ERα-negative than in ERα-positive cells. In total, 3 upregulated and 17 downregulated TFs were screened out by knocked-down expression of ERRα in all EC cells. Among them, the upregulated TFs organic cation transporter 3/4(Oct3/4), hepatic nuclear factor 4 (HNF4), HNF4 and chicken ovalbumin upstream TF (COUP-TF) as well as downregulated transcription factor EB (TFEB) were found to be statistically significant (P<0.05). Conclusion Targeting ERRα provides a promising novel endocrine therapeutic strategy.
Dry Electrode Optimization for Wrist-based Electrodermal Activity Monitoring

Recent years of healthcare research has shown an increasing demand and interest in wearable personal healthcare systems. This, when combined with the superior utility of Electrodermal activity (EDA) for diverse applications ranging from market research to human stress and sleep quality analysis to seizure detection have driven significant interest towards optimizing dry electrode designs for EDA monitoring. The conventional wet adhesive Ag/AgCl electrodes, which is the gold standard, is used almost universally and provide excellent signal quality. However, they are less comfortable and not suitable for wearable scenarios that involve continuous long-term monitoring. This study focuses on identifying an optimum dry electrode configuration for monitoring EDA from the wrist. It is hypothesized that parameters like electrode material, interelectrode distance and anatomical location of measurement influence the dry electrode design for EDA detection. Accordingly, stainless steel, silver, brass and gold electrodes were fabricated with geometry and dimensions similar to that of commercially available standard wet electrodes. The fabricated electrodes were further investigated with interelectrode separations of 2 cm and 4 cm, both on the ventral and dorsal surfaces of the wrist at 6 cm distance from the carpus, thereby constituting 16 dry electrode configurations. An experimental protocol that spanned over 10 hours per subject was designed to investigate these configurations systematically and to identify the one that yielded the highest correlation with the gold standard. Also, the stabilization period for these dry electrode configurations were quantified as the time taken by the EDA signal to reach within ± 5% of its final value. The experimental study done on 7 subjects (3 females and 4 males, age: 23.3 ± 2.8 years; mean ± SD) illustrated that silver electrodes worn on the dorsal surface of the wrist with an interelectrode separation of 4 cm performed consistently well on all subjects with an average Pearson correlation coefficient of 0.899 ± 0.036, following an average stabilization time of 27.1 minutes.
Contract-Based Incentive Mechanism for LTE Over Unlicensed Channels

In this paper, a novel economic approach, based on the framework of contract theory, is proposed for providing incentives for LTE over unlicensed channels (LTE-U) in cellular networks. In this model, a mobile network operator (MNO) designs and offers a set of contracts to the users to motivate them to accept being served over the unlicensed bands. A practical model in which the information about the quality-of-service (QoS) required by every user is not known to the MNO and other users is considered. For this contractual model, the closed-form expression of the price charged by the MNO for every user is derived and the problem of spectrum allocation is formulated as a matching game with incomplete information. For the matching problem, a distributed algorithm is proposed to assign the users to the licensed and unlicensed spectra. The simulation results show that the proposed pricing mechanism can increase the fraction of users that achieve their QoS requirements by up to 45% compared to classical algorithms that do not account for users requirements. Moreover, the performance of the proposed algorithm in the case of incomplete information is shown to approach the performance of the same mechanism with complete information.
Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.
Random Telegraph Signal in Proton Irradiated Single-Photon Avalanche Diodes

Single-photon avalanche diodes (SPADs) in the CMOS technology are very attractive solution for photon detection due to the excellent timing resolution achievable. Unfortunately, such devices suffer from large values of the dark count (DC) pedestals. In this paper, we analyzed a test chip containing SPADs with different layouts, implemented in the 150-nm CMOS technology. The behavior of such devices has been investigated after proton irradiation. It is observed that, after irradiation, the DC rate switches between two or more discrete levels, phenomenon known as random telegraph signal (RTS). The effect is related to the density and distribution of defects in the semiconductor lattice. RTS characteristics have been studied as the function of both temperature and bias voltage. Discussion of results and main hypotheses on defect types responsible for RTS are reported.
Apelin Effects Migration and Invasion Abilities of Colon Cancer Cells

Colon cancer is one of the most common cancer types. Its positive correlation with general obesity has led to increasing amounts of research focusing on the role of adipokines in colon cancer development. Apelin is a peptide released by adipose tissue that could affect many cellular processes connected with carcinogenesis. In this study, we examined the role of apelin in the motility regulation of colon cancer cells. We showed that the effect of four different apelin peptides increased the ability of cancer cells to migrate and invade examined cells trough influencing migratory protrusions formation and actin cytoskeleton rearrangement. Additionally, using confocal microscopy, we noticed that apelin stimulated the proteolytic activity of cancer cells, especially increasing the level of membrane-type 1 matrix metalloprotease. Taken together, apelin increased the movement of colon cancer cells through several possible mechanisms. Moreover, better understanding the process through which apelin regulates cancer development is still necessary to the creation of novel anti-cancer therapy.