Miracle-dz/UniFAR-FTUs huggingface dataset:
The ARPE-19 Cell Line: Mortality Status and Utility in Macular Degeneration Research

Abstract Purpose: The present report examines several subcultures of a single sample of ARPE-19 cells to determine their status with respect to cell mortality. If a transformation from mortal to immortal has occurred in these cells, it may impact their characteristics and, thereby, their utility for modeling natural retinal pigment epithelial (RPE) cells. Methods: Five separate subcultures of ARPE-19 cells were grown as recommended by the supplier. During the course of culture, they were periodically monitored for signs of mortality including erosion of telomeres, increased senescence-associated beta-galactosidase (SABG) staining, altered morphology and reduced viability with an increased population doubling level (PDL). There were also observed for signs of immortality including continuous growth to very high population doubling levels and maintenance of short telomere lengths. Results: Each of the subcultures showed both mortal and immortal characteristics. Telomere erosion, increased SABG staining, changes in cell morphology and a modest drop in cell viability took place within a range of population doublings (59–77) in which cell senescence would be expected to occur. The cultures, however, continued to proliferate even after signs of senescence had appeared, with one subculture propagating to 257 population doublings. In addition, little further telomere erosion occurred at high PDL. Conclusion: These results suggest that the ARPE-19 subcultures contained both mortal and immortal cells. Since no transformation event was witnessed during the study, it appears likely that both types of cells were present in the original sample. Based on the proportion of cells demonstrating senescence-related changes, the mortal cells were estimated to comprise approximately 27% of the total culture. Because of the differences that can exist between normal and immortalized cells, and given the large proportion of ARPE-19 cells that are immortalized, discretion should be exercised when using ARPE-19 cells to model native RPE cells for the study of retinal diseases such as AMD.
Measures of Consistency for DEMATEL Method

The current studies of using decision-making trial and evaluation laboratory (DEMATEL) method assume that the survey results from a group of people are reliable. However, the assumption might not be always true. In this study, we propose an integrated approach of using corrected item-total correlation and split-half methods to evaluate the consistency from the survey data. A case is illustrated to show that the proposed approach can identify those who have different opinions from the others. From managerial implications, the decision maker can further examine whether these different opinions should be taken into consideration when DEMATEL method is used.
A Bilevel Quadratic–Quadratic Fractional Programming through Fuzzy Goal Programming approach

This paper proposed a new model of quadratic fractional programming problem where our purpose is to study the quadratic fractional programming problem through fuzzy goal programming procedure by utilizing the bilevel linear programming. The bilevel is a class of multilevel optimization hierarchy with two decision levels and each objective function in both decision maker levels has fractional form with quadratic function in numerator as well as in denominator. In this paper we construct two bilevel quadratic programming problems from one bilevel quadratic fractional programming problem by separating the numerator and denominator in fractional objective function of each decision maker. Next our purpose isto solve both bilevel quadratic programming problems separately and thus to form a solution procedure for our proposed model which named as Bilevel Quadratic –Quadratic Fractional Programming Problem.
Wavelet based Extraction of Blood Vessels

An algorithm for the segmentation of blood vessels based on the correlation of different wavelet scales is presented. First the wavelet coefficients are computed for a defined number of scales and then the correlation between the corresponding coefficients of two consecutive scales is computed. The normalized product is used as a reference threshold for retaining original wavelet coefficients. If the normalized product is greater than the corresponding original wavelet coefficient, the original coefficient is retained for image reconstruction by inverse wavelet transform, otherwise the coefficient is changed with zero value. Low frequency wavelet coefficients matrix is not used in image reconstruction process as we want only the edge information. The proposed algorithm is quite general and can be used for the extraction of any type of blood vessels and provides very promising results.
A HYBRID AUTOMATON REPRESENTATION OF SIMULATED MOVING BED PROCESSES

Abstract Simulated Moving Bed (SMB) chromatographic separation processes show typical hybrid phenomena: discrete state jumps and switching dynamics. The SMB principle and two modelling approaches based on hybrid automaton are presented and discussed within the context of hybrid systems theory. It is shown how these models are affected by open-loop and closed-loop control.
Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab

Patients experiencing dose-limiting adverse effects after progressing on ipilimumab were enrolled in a trial of nivolumab. Nivolumab was active, safe and may not be needed indefinitely. The presence of fewer pretreatment myeloid-derived suppressor cells was associated with better responses and survival. The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3–4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%–41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3–4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%–82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3–4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. Cancer Immunol Res; 4(4); 345–53. ©2016 AACR.
In vivo trans‐synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI)

Small focal injections of manganese ion (Mn2+) deep within the mouse central nervous system combined with in vivo high‐resolution MRI delineate neuronal tracts originating from the site of injection. Previous work has shown that Mn2+ can be taken up through voltage‐gated Ca2+ channels, transported along axons, and across synapses. Moreover, Mn2+ is a paramagnetic MRI contrast agent, causing positive contrast enhancement in tissues where it has accumulated. These combined properties allow for its use as an effective MRI detectable neuronal tract tracer. Injections of low concentrations of MnCl2 into either the striatum or amygdala produced significant contrast enhancement along the known neuronal circuitry. The observed enhancement pattern is different at each injection site and enhancement of the homotopic areas was observed in both cases. Ten days postinjection, the Mn2+ had washed out, as evidenced by the absence of positive contrast enhancement within the brain. This methodology allows imaging of neuronal tracts long after the injection of the ion because Mn2+ concentrates in active neurons and resides for extended periods of time. With appropriate controls, differentiation of subsets of neuronal pathways associated with behavioral and pharmacological paradigms should be feasible. Magn Reson Med 50:33–39, 2003. © 2003 Wiley‐Liss, Inc.
Children with autism spectrum disorder have an exceptional explanatory drive

An “explanatory drive” motivates children to explain ambiguity. Individuals with autism spectrum disorders are interested in how systems work, but it is unknown whether they have an explanatory drive. We presented children with and without autism spectrum disorder unsolvable problems in a physical and in a social context and evaluated problem-solving and explanation-seeking responses. In the physical context (but not the social context), the children with autism spectrum disorder showed a stronger explanatory drive than controls. Importantly, the number of explanatory behaviors made by children with autism spectrum disorder in the social context was independent of social and communicative impairments. Children with autism spectrum disorder did not show an exceptional explanatory drive in the social domain. These results suggest that children with autism spectrum disorder have an explanatory drive and that the explanatory drive may be domain specific.
An improved vertex-clustering-based progressive mesh encoder

In this work, we propose improvements on a state-of-the-art scheme for progressive triangular mesh compression, which is based on hierarchical vertex clustering. Specifically, we fix several shortcomings of that scheme including quantization error accumulation, false facet generation and lack of facet orientation encoding. In addition, the resultant mesh encoder yields better rate-distortion performance than another state-of-the-art one on our test model, as demonstrated by the experiments.
A Novel Technique of Feature Extraction Based on Local and Global Similarity Measure for Protein Classification

The paper aims to propose a novel approach for extracting features from protein sequences. This approach extracts only 6 features for each protein sequence which are computed by globally considering the probabilities of occurrences of the amino acids in different position of the sequences within the superfamily which locally belongs to the six exchange groups. Then, these features are used as an input for Neural Network learning algorithm named as Boolean-Like Training Algorithm (BLTA). The BLTA classifier is used to classify the protein sequences obtained from the Protein Information Resource (PIR). To investigate the efficacy of proposed feature extraction approach, the experimentation is performed on two superfamilies, namely Ras and Globin. Across tenfold cross validation, the highest Classification Accuracy achieved by proposed approach is 94.32±3.52 with Computational Time 6.54±0.10 (s) is remarkably better in comparison to the Classification Accuracies achieved by other approaches. The experimental results demonstrate that the proposed approach extracts the minimum number of features for each protein sequence. Therefore, it results in considerably potential improvement in Classification Accuracy and takes less Computational Time for protein sequence classification in comparison with other well-known feature extraction approaches.
The NLstart2run study: Incidence and risk factors of running‐related injuries in novice runners

Running is a popular form of physical activity, despite of the high incidence of running‐related injuries (RRIs). Because of methodological issues, the etiology of RRIs remains unclear. Therefore, the purposes of the study were to assess the incidence of RRIs and to identify risk factors for RRIs in a large group of novice runners. In total, 1696 runners of a 6‐week supervised “Start to Run” program were included in the NLstart2run study. All participants were aged between 18 and 65, completed a baseline questionnaire that covered potential risk factors, and completed at least one running diary. RRIs were registered during the program with a weekly running log. An RRI was defined as a musculo‐skeletal complaint of the lower extremity or back attributed to running and hampering running ability for three consecutive training sessions. During the running program, 10.9% of the runners sustained an RRI. The multivariable Cox regression analysis showed that a higher age, higher BMI, previous musculo‐skeletal complaints not attributed to sports and no previous running experience were related to RRI. These findings indicate that many novice runners participating in a short‐term running program suffer from RRIs. Therefore, the identified risk factors should be considered for screening and prevention purposes.
Astrocyte elevated gene-1 induces protective autophagy

Astrocyte-elevated gene-1 (AEG-1) expression increases in multiple cancers and plays a crucial role in oncogenic transformation and angiogenesis, which are essential components in tumor cell development, growth, and progression to metastasis. Moreover, AEG-1 directly contributes to resistance to chemotherapeutic drugs, another important hallmark of aggressive cancers. In the present study, we document that AEG-1 mediates protective autophagy, an important regulator of cancer survival under metabolic stress and resistance to apoptosis, which may underlie its significant cancer-promoting properties. AEG-1 induces noncanonical autophagy involving an increase in expression of ATG5. AEG-1 decreases the ATP/AMP ratio, resulting in diminished cellular metabolism and activation of AMP kinase, which induces AMPK/mammalian target of rapamycin-dependent autophagy. Inhibition of AMPK by siAMPK or compound C decreases expression of ATG5, ultimately attenuating AEG-1–induced autophagy. AEG-1 protects normal cells from serum starvation-induced death through protective autophagy, and inhibition of AEG-1–induced autophagy results in serum starvation-induced cell death. We also show that AEG-1–mediated chemoresistance is because of protective autophagy and inhibition of AEG-1 results in a decrease in protective autophagy and chemosensitization of cancer cells. In summary, the present study reveals a previously unknown aspect of AEG-1 function by identifying it as a potential regulator of protective autophagy, an important feature of AEG-1 that may contribute to its tumor-promoting properties.
Longitudinal Genotyping of Candida dubliniensis Isolates Reveals Strain Maintenance, Microevolution, and the Emergence of Itraconazole Resistance

ABSTRACT We investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.
Residues phosphorylated by TFIIH are required for E2F‐1 degradation during S‐phase

The transcription factor E2F‐1 plays a key role in regulating cell cycle progression. Accordingly, E2F‐1 activity is itself tightly controlled by a series of transcriptional and post‐transcriptional events. Here we show that the E2F‐1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F‐1 phosphorylation observed in cell extracts and that endogenous E2F‐1 interacts in vivo with p62, a component of TFIIH, during S phase. When the two phosphorylation sites in E2F‐1 are mutated to alanine, the stability of the E2F‐1 activation domain is greatly increased. These results suggest that TFIIH‐mediated phosphorylation of E2F‐1 plays a role in triggering E2F‐1 degradation during S phase.
Detection and removal of switching noise in push-to-talk and voice operated exchange communications systems

This paper addresses the detection and removal of key clicks in the NATO non-native Air Traffic Control database. Key clicks are impulse-like noises generated in Push-to-Talk (PTT) and Voice Operated eXchange (VOX) communications systems. The removal of key clicks can improve the quality of the signal for both listening and machine processing. The detection of key clicks could also assist in other applications, such as speech segmentation on these types of channels. The approach taken was to first apply a Recursive Least Squares (RLS) whitening filter to augment the key clicks. Outlier detection based on order statistics was then applied to detect the candidate key click samples. Finally, sample values extending to the second zero crossing prior to a detected key click and to the third zero crossing following a detected key click were set to zero to remove the key clicks. With this approach 98.3% detection of the key clicks with only 0.19% false alarms was obtained.
Doubly balanced spatial sampling with spreading and restitution of auxiliary totals

A new spatial sampling method is proposed in order to achieve a double property of balancing. The sample is spatially balanced or well spread so as to avoid selecting neighbouring units. Moreover, the method also enables to satisfy balancing equations on auxiliary variables available on all the sampling units because the Horvitz–Thompson estimator is almost equal to the population totals for these variables. The method works with any definition of distance in a multidimensional space and supports the use of unequal inclusion probabilities. The algorithm is simple and fast. Examples show that the method succeeds in using more information than the local pivotal method, the cube method and the Generalized Random‐Tessellation Stratified sampling method, and thus performs better. An estimator of the variance for this sampling design is proposed in order to lead to an inference that takes the effect of the sampling design into account. Copyright © 2012 John Wiley & Sons, Ltd.
Voyage and Immobility in J. M. G. Le Clézio's Désert and La quarantaine

quarantaine, to West Africa in Onitsha, to North Africa, Europe, and even America in Desert and Poisson d'or, and to the Middle East in Etoile errante. I have spent many a quiet evening at home, in the comfort of my reclining chair, accompanying Le Clezio around the world, exploring places which I have never visited and perhaps never will. Yet at the same time I have been immobile with Le Clezio, never leaving my chair as I sit, transfixed, immersing myself in the exotic locales he depicts, and as I immobilize the text, lingering over and rereading the rich descriptive passages that so capture my imagination. But I have also literally traveled with Le Clezio, as copies of his works have accompanied me on my own voyages, less adventurous to be sure: home for the holidays and to the MLA convention in Washington, as I prepared to write this article. I might well have chosen other substantives in the formation of the title of this study in an attempt to encapsulate the two features of Le Clezio's works which are the focus here. Instead of voyages I might have spoken of travel, movement, dislocation or relocation, wandering, flight or escape, yet without failing to convey the fundamental quality of these works that interests me. By the same token, instead of immobility I might have chosen stasis, inactivity, waiting, or confinement, all equally representative and appropriate terms. But I chose voyage and immobility for three specific yet simple reasons. First, these two words are frequently utilized by Le Clezio himself in the works to be considered here: Desert
Effects of multidimensional child poverty on children’s mental health in Mainland China

This study aimed to investigate the effects of multidimensional child poverty on children’s mental health in Mainland China. The data were based on a survey of children in 2015 conducted by multi-stage cluster random sampling method in Xiushui, where levels of poverty are very high. Structural equation model was adopted to analyze the data and test the hypothesized model. Results showed that multidimensional child poverty had a significant effect on both negative mental health and positive mental health of children, and the seven indicators of multidimensional child poverty all had slightly different effects on children’s mental health.