Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonsense-mediated mRNA decay factor Upf2 exists in both the nucleoplasm and the cytoplasm

Upf2 protein predominantly localizes to the cytoplasmic fraction, and binds to the exon junction complex (EJC) on spliced mRNA. The present study aimed to determine the cellular site where the interaction between Upf2 and EJC occurs. First, the cell lysate was fractionated into the cytoplasm and nucleoplasm, and western blotting to detect levels of Upf2 protein was performed. Upf2 was clearly detected in the cytoplasm and in the nucleoplasm. Secondly, immunostaining was performed, and the majority of Upf2 was detected in the cytoplasmic perinuclear region; a small quantity of Upf2 was detected in the intranuclear region. RNase treatment of the cells reduced the Upf2 immunostained signal. The immune-purified fractions containing nuclear and cytoplasmic Upf2 also contained one of the EJC core factors, RBM8A. These results implied the existence of Upf2 in the nucleoplasm and the cytoplasm, and it appeared to be involved in the construction of the mRNA complex. In order to verify the construction of Upf2-binding EJC in the nucleoplasm, an in situ proximity ligation assay was performed with anti-Upf2 and anti-RBM8A antibodies. These results demonstrated that their interaction occurred not only in the cytoplasmic region, but also in the intranuclear region. Taken together, these results suggested that Upf2 combines with EJC in both the cytoplasmic and the intranuclear fractions, and that it is involved in mRNA metabolism in human cells.
Sphingolipids: Key Regulators of Apoptosis and Pivotal Players in Cancer Drug Resistance

Drug resistance elicited by cancer cells still constitutes a huge problem that frequently impairs the efficacy of both conventional and novel molecular therapies. Chemotherapy usually acts to induce apoptosis in cancer cells; therefore, the investigation of apoptosis control and of the mechanisms used by cancer cells to evade apoptosis could be translated in an improvement of therapies. Among many tools acquired by cancer cells to this end, the de-regulated synthesis and metabolism of sphingolipids have been well documented. Sphingolipids are known to play many structural and signalling roles in cells, as they are involved in the control of growth, survival, adhesion, and motility. In particular, in order to increase survival, cancer cells: (a) counteract the accumulation of ceramide that is endowed with pro-apoptotic potential and is induced by many drugs; (b) increase the synthesis of sphingosine-1-phosphate and glucosylceramide that are pro-survivals signals; (c) modify the synthesis and the metabolism of complex glycosphingolipids, particularly increasing the levels of modified species of gangliosides such as 9-O acetylated GD3 (αNeu5Ac(2-8)αNeu5Ac(2-3)βGal(1-4)βGlc(1-1)Cer) or N-glycolyl GM3 (αNeu5Ac (2-3)βGal(1-4)βGlc(1-1)Cer) and de-N-acetyl GM3 (NeuNH(2)βGal(1-4)βGlc(1-1)Cer) endowed with anti-apoptotic roles and of globoside Gb3 related to a higher expression of the multidrug resistance gene MDR1. In light of this evidence, the employment of chemical or genetic approaches specifically targeting sphingolipid dysregulations appears a promising tool for the improvement of current chemotherapy efficacy.
Spectrum of activity of levofloxacin against nontuberculous mycobacteria and its activity against the Mycobacterium avium complex in combination with ethambutol, rifampin, roxithromycin, amikacin, and clofazimine

The spectrum of activity of levofloxacin was initially determined against 29 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs. Levofloxacin MICs were 1 to 2 dilutions lower compared with those obtained for ofloxacin and 8 to 64 dilutions lower compared with those obtained for its D-isomer. Levofloxacin MICs were below its peak level in serum (5.5 micrograms/ml following administration of a single oral dose of 350 mg) for 25 of 29 isolates tested. It possessed MICs below its peak level in serum for M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, M. chelonei, M. abcessus, M. fortuitum, and M. peregrinum. Regarding the M. avium complex, the MICs of levofloxacin for 11 clinical isolates (7 from human immunodeficiency virus-positive patients and 4 from human immunodeficiency virus-negative patients) were 1 to 2 dilutions lower than those of ofloxacin. Among 20 isolates belonging to 12 pathogenic mycobacterial species, the MBC/MIC ratios varied from 1 to 4 for levofloxacin and 2 to 4 for ofloxacin. When drug combinations were screened by using the radiometric x/y quotient methodology against five M. avium complex isolates, levofloxacin activity against all five isolates was enhanced by ethambutol and activity against three isolates was enhanced by clofazimine. Screening of three-drug combinations showed that the combination levofloxacin-ethambutol with a third potential anti-M. avium drug (rifampin, roxithromycin, amikacin, or clofazimine) resulted in enhanced activity for all 20 drug combinations screened.
The Effect of Implicit–Explicit Followership Congruence on Benevolent Leadership: Evidence from Chinese Family Firms

Benevolent leadership, a traditional Chinese leadership style generated under the influence of Confucianism, has been under growing discussion since its proposal. However, existing research has focused mainly on the consequences of benevolent leadership, and research probing into its antecedents is scarce. To fill such research gap, the current study aims to explore the effect of the congruence between implicit positive followership prototype (PFP) and explicit positive followership trait (PFT) on benevolent leadership. Polynomial regression combined with the response surface methodology was used to test the hypotheses herein. The results, based on a sample of 241 leader–follower dyads from four Chinese family firms, indicated the following: (1) benevolent leadership is higher when leader PFP is congruent with follower PFT than when they are incongruent; (2) in cases of congruence, benevolent leadership is higher when leader PFP and follower PFT are both high rather than low; (3) in the case of incongruence, there is no significant difference for the level of benevolent leadership in two scenarios: “low leader PFP – high follower PFT” and “high leader PFP – low follower PFT”.
Nonauditory Events of a Behavioral Procedure Activate Auditory Cortex of Highly Trained Monkeys

A central tenet in brain research is that early sensory cortex is modality specific, and, only in exceptional cases, such as deaf and blind subjects or professional musicians, is influenced by other modalities. Here we describe extensive cross-modal activation in the auditory cortex of two monkeys while they performed a demanding auditory categorization task: after a cue light was turned on, monkeys could initiate a tone sequence by touching a bar and then earn a reward by releasing the bar on occurrence of a falling frequency contour in the sequence. In their primary auditory cortex and posterior belt areas, we found many acoustically responsive neurons whose firing was synchronized to the cue light or to the touch or release of the bar. Of 315 multiunits, 45 exhibited cue light-related firing, 194 exhibited firing that was related to bar touch, and 268 exhibited firing that was related to bar release. Among 60 single units, we found one neuron with cue light-related firing, 21 with bar touch-related firing, and 36 with release-related firing. This firing disappeared at individual sites when the monkeys performed a visual detection task. Our findings corroborate and extend recent findings on cross-modal activation in the auditory cortex and suggests that the auditory cortex can be activated by visual and somatosensory stimulation and by movements. We speculate that the multimodal corepresentation in the auditory cortex has arisen from the intensive practice of the subjects with the behavioral procedure and that it facilitates the performance of audiomotor tasks in proficient subjects.
Feedback model predictive control by randomized algorithms

In this paper we present a further development of an algorithm for stochastic disturbance rejection in model predictive control with input constraints based on randomized algorithms. The algorithm presented in [1] can solve the problem of stochastic disturbance rejection approximately but with high accuracy at the expense of a large computational effort. The algorithm described here uses a predefined controller structure in the optimization and it is significantly less computationally demanding but with a price of some performance loss. Via an example it is shown that the algorithm gives considerable reduction in the computational time and that performance loss is rather small compared to the algorithm in [1].
METODE PEMBELAJARAN PENGETAHUAN AWAL TERHADAP KEMAMPUAN MEMBACA PEMAHAMAN SISWA

Abstrak : Penelitian ini bertujuan untuk mengetahui pengaruh metode pembelajaran dan pengetahuan awal siswa terhadap kemampuan membaca pemahaman. Penelitian ini dilakukan pada siswa kelas V SD Negeri 1 Depok Kabupaten Cirebon pada tahun 2015 dengan 60 sampel. Pengambilan data diperoleh melalui tes analisis Varian (ANAVA) dua jalur dengan desain treatmeant by level 2 x 2. Hasil penelitian menunjukkan bahwa: (1) Hasil kemampuan membaca pemahaman siswa yang menggunakan metode problem based learning lebih baik dari pada siswa yang menggunakan metode directed reading thinking activities. (2) Hasil kemampuan membaca pemahaman siswa yang pengetahuan awal tinggi dan belajar dengan metode problem based learning lebih baik dari pada metode directed reading thinking activities, (3) Hasil kemampuan membaca pemahaman siswa yang pengetahuan awal rendah dan belajar dengan metode problem based learning lebih baik dari pada metode directed reading thinking activities Kata Kunci: Metode pembelajaran, pengetahuan awal, membaca pemahaman Abstrak : Penelitian ini bertujuan untuk mengetahui pengaruh metode pembelajaran dan pengetahuan awal siswa terhadap kemampuan membaca pemahaman. Penelitian ini dilakukan pada siswa kelas V SD Negeri 1 Depok Kabupaten Cirebon pada tahun 2015 dengan 60 sampel. Pengambilan data diperoleh melalui tes analisis Varian (ANAVA) dua jalur dengan desain treatmeant by level 2 x 2. Hasil penelitian menunjukkan bahwa: (1) Hasil kemampuan membaca pemahaman siswa dengan metode problem based learning lebih baik dari pada siswa dengan metode directed reading thinking activities. (2) Hasil kemampuan membaca pemahaman siswa yang pengetahuan awal tinggi dan belajar dengan metode problem based learning lebih baik dari pada metode directed reading thinking activities, (3) Hasil kemampuan membaca pemahaman siswa dan belajar dengan metode problem based learning lebih baik dari pada metode directed reading thinking activities Kata Kunci: Metode pembelajaran, pengetahuan awal, membaca pemahaman
Prevalence and Fate of Carbapenemase Genes in a Wastewater Treatment Plant in Northern China

Carbapenemase-producing strains of bacteria, which were primarily found in the medical field, have increasingly been found in the environment, thus posing potential risks to public health. One possible way for carbapenemase genes to enter the environment is via wastewater. Therefore, the goal of this study was to determine the occurrence and fate of five high-risk carbapenemase genes in a wastewater treatment plant (WWTP) in northern China using real-time qPCR. Results showed that the blaKPC-2, blaGES-1, and blaIMP-1 genes prevailed throughout all processing stages (even in the chlorination disinfection unit) in the WWTP, whereas the blaVIM-2 and blaOXA-48 genes were not detected in all samples. Worryingly, considerable amounts of carbapenemase genes ((1.54 ± 0.61) × 103 copies/mL to (2.14± 0.41) × 105 copies/mL) were detected in WWTP effluent samples, while the majority of the carbapenemase genes were transported to the dewatered sludge with concentrations from (6.51 ± 0.14) × 109 copies/g to (6.18 ± 0.63) × 1010 copies/g dry weight. Furthermore, a total of 97 KPC-2-producing strains, belonging to 8 bacterial genera, were isolated from the WWTP. Sequencing of 16S rRNA revealed that most of KPC-2 producing isolates were opportunistic pathogens, including Klebsiella spp. (10.3%), Enterococcus spp. (11.3%), Acinetobacter spp. (19.6%), Escherichia spp. (12.4%), Shigella spp. (17.5%), Stenotrophomonas spp. (10.3%) and Wautersiella spp. (9.3%). Moreover, blaKPC-2 genes were identified for the first time in Paenibacillus spp. isolates (an indigenous bacteria), indicating an increased risk of horizontal transfer between clinical pathogens and environmental bacteria. Indeed, a conjugation experiment demonstrated transfer of the blaKPC-2 gene to an E.coli J53 strain from a Klebsiella strain isolated from the WWTP. To our knowledge, this is the first study to obtain Paenibacillus spp. isolates carrying the carbapenemase gene and to quantify the abundance of carbapenemase genes in the environment.
Submapping SLAM based on acoustic data from a 6-DOF AUV

Abstract Autonomous Underwater Vehicles (AUVs) need positioning systems besides the Global Positioning System (GPS), since GPS does not work in underwater scenarios. Possible solutions are the Simultaneous Localization and Mapping (SLAM) algorithms. SLAM algorithms aim to build a map while simultaneously localizing the vehicle within this map. However, they offer limited performance when faced with large scale scenarios. For instance, they do not create consistent maps for large areas, mainly because uncertainties increase with the scale of the scenario. In addition, the computational cost increases with the map size. The use of local maps reduces computational cost and improves map consistency. Following this idea, in this paper we propose a new SLAM approach that uses independent local maps together with a global level stochastic map. The global level contains the relative transformations between local maps. These local maps are updated once a new loop is detected. Local maps that are sharing a high number of features are updated through fusion, maintaining the correlation between landmarks and vehicle. Experimental results on real data obtained from the REMUS-100 AUV show that our approach is able to obtain large map areas consistently.
Absence of mechanical loading in utero influences bone mass and architecture but not innervation in Myod‐Myf5‐deficient mice

Although the responses of bone to increased loading or exercise have been studied in detail, our understanding of the effects of decreased usage of the skeleton has been limited by the scarcity of suitable models. Such models should ideally not affect bone innervation, which appears to be a mediator of physiological responses of bone to unloading. MyoD–/–/Myf5–/– (dd/ff) mice lack skeletal muscle, so the fetuses develop without any active movement in utero and die soon after birth. We used micro‐compter tomography and histology to analyse their bone development and structure during endochondral ossification in parallel with the establishment of bone innervation. Long bones from mutant mice were found to be profoundly different from controls, with shorter mineralized zones and less mineralization. They lacked many characteristics of adult bones – curvatures, changes in shaft diameter and traction epiphyses where muscles originate or insert – that were evident in the controls. Histologically, dd/ff mice showed the same degree of endochondral development as wild‐type animals, but presented many more osteoclasts in the newly layed bone. Innervation and the expression pattern of semaphorin‐3A signalling molecules were not disturbed in the mutants. Overall, we have found no evidence for a major defect of development in dd/ff mice, and specifically no alteration or delay in endochondral ossification and bone innervation. The altered morphological features of dd/ff mice and the increased bone resorption show the role of muscle activity in bone shaping and the consequences of bone unloading.
Closed timelike curves and holography in compact plane waves

We discuss plane wave backgrounds of string theory and their relation to G? del-like universes. This involves a twisted compactification along the direction of propagation of the wave, which induces closed timelike curves. We show, however, that no such curves are geodesic. The particle geodesics and the preferred holographic screens we find are qualitatively different from those in the G? del-like universes. Of the two types of preferred screen, only one is suited to dimensional reduction and/or T-duality, and this provides a ``holographic protection'' of chronology. The other type of screen, relevant to an observer localized in all directions, is constructed both for the compact and non-compact plane waves, a result of possible independent interest. We comment on the consistency of field theory in such spaces, in which there are closed timelike (and null) curves but no closed timelike (or null) geodesics.
Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound

The genetic etiology of non-aneuploid fetal structural abnormalities is typically investigated by karyotyping and array-based detection of microscopically detectable rearrangements, and submicroscopic copy-number variants (CNVs), which collectively yield a pathogenic finding in up to 10% of cases. We propose that exome sequencing may substantially increase the identification of underlying etiologies. We performed exome sequencing on a cohort of 30 non-aneuploid fetuses and neonates (along with their parents) with diverse structural abnormalities first identified by prenatal ultrasound. We identified candidate pathogenic variants with a range of inheritance models, and evaluated these in the context of detailed phenotypic information. We identified 35 de novo single-nucleotide variants (SNVs), small indels, deletions or duplications, of which three (accounting for 10% of the cohort) are highly likely to be causative. These are de novo missense variants in FGFR3 and COL2A1, and a de novo 16.8 kb deletion that includes most of OFD1. In five further cases (17%) we identified de novo or inherited recessive or X-linked variants in plausible candidate genes, which require additional validation to determine pathogenicity. Our diagnostic yield of 10% is comparable to, and supplementary to, the diagnostic yield of existing microarray testing for large chromosomal rearrangements and targeted CNV detection. The de novo nature of these events could enable couples to be counseled as to their low recurrence risk. This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic abnormalities through the application of next-generation sequencing.
Patterns in the external history of Portuguese collections with translations of Polish literature (1855–2009)

This paper sets out to identify and analyse patterns in the external history of Portuguese collections with translations of Polish literature between 1855 and 2009. By doing so, it will provide preliminary insights into how these collections have presented Polish literature to the Portuguese readership and, ultimately, how they have contributed to the canonization of Polish authors/texts and the formation of cultural relations between the two (semi)peripheral languages/cultures concerned. To achieve these goals, in the first part relevant information regarding the corpus will be provided. Secondly, the methodology for analysing collections will be briefly elucidated. Thirdly, the results of the study will be presented. More specifically, the findings of preliminary analysis leading to statistical coding of peritextual elements will be described, six collection profiles will be examined and chronological patterns in the canonization of a given Polish author will be traced. Finally, the paper’s findings will be summarized and hypotheses to be tested in future research will be proposed.
The impact of climate change in Africa

This paper is concerned with the fact that African nations are among the lightest polluters, yet analysts say they will suffer the most from climate change in their pursuit of water and food security, sustainable development, and political and economic sustainability. Therefore the paper reviews the relationships among climate change, water and food security, conflicts, and development. It also argues that there is a need for climate change information in Africa and reviews the status of international climate agreements related to adaptation, mitigation and compensation. In addition, the paper argues that even if climate change by its nature may not necessarily lead to violent interstate conflicts, scarcity of water and food in Africa has already nurtured political tensions among nations, thus retarding efforts towards sustainable development.
Riboflavin/UVA Collagen Cross-Linking-Induced Changes in Normal and Keratoconus Corneal Stroma

Purpose To determine the effect of Ultraviolet-A collagen cross-linking with hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen ultrastructure in normal and keratoconus ex vivo human corneas. Methods Using small-angle X-ray scattering, measurements of collagen D-periodicity, fibril diameter and interfibrillar spacing were made at 1 mm intervals across six normal post-mortem corneas (two above physiological hydration (swollen) and four below (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen; one unswollen), before and after hypo-osmolar cross-linking. The same parameters were measured in three other unswollen normal corneas before and after iso-osmolar cross-linking and in three pairs of swollen normal corneas, in which only the left was cross-linked (with iso-osmolar riboflavin). Results Hypo-osmolar cross-linking resulted in an increase in corneal hydration in all corneas. In the keratoconus corneas and unswollen normal corneas, this was accompanied by an increase in collagen interfibrillar spacing (p<0.001); an increase in fibril diameter was also seen in two out of four unswollen normal corneas and one unswollen keratoconus cornea (p<0.001). Iso-osmolar cross-linking resulted in a decrease in tissue hydration in the swollen normal corneas only. Although there was no consistent treatment-induced change in hydration in the unswollen normal samples, iso-osmolar cross-linking of these corneas did result in a compaction of collagen fibrils and a reduced fibril diameter (p<0.001); these changes were not seen in the swollen normal corneas. Collagen D-periodicity was not affected by either treatment. Conclusion The observed structural changes following Ultraviolet-A cross-linking with hypo-osmolar or iso-osmolar riboflavin solutions are more likely a consequence of treatment-induced changes in tissue hydration rather than cross-linking.
Singularity of the Hessian in Deep Learning

We look at the eigenvalues of the Hessian of a loss function before and after training. The eigenvalue distribution is seen to be composed of two parts, the bulk which is concentrated around zero, and the edges which are scattered away from zero. We present empirical evidence for the bulk indicating how overparametrized the system is, and for the edges indicating the complexity of the input data.