Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipid–Saporin Nanoparticles for the Intracellular Delivery of Cytotoxic Protein to Overcome ABC Transporter-Mediated Multidrug Resistance In Vitro and In Vivo

Although the judicious use of anticancer drugs that target one or more receptor tyrosine kinases constitutes an effective strategy to attenuate tumor growth, drug resistance is commonly encountered in cancer patients. The ATP-binding cassette transporters are one of the major contributors to the development of multidrug resistance as their overexpression significantly decreases the intracellular concentration and thus, the efficacy of certain anticancer drugs. Therefore, the development of treatment strategies that would not be susceptible to efflux or excretion by specific ABC transporters could overcome resistance to treatment. Here, we investigated the anticancer efficacy of saporin, a ribosome-inactivating protein. Since saporin has poor permeability across the cell membrane, it was encapsulated in a lipid-based nanoparticle system (EC16-1) that effectively delivered the formulation (EC16-1/saporin) intracellularly and produced anti-cancer efficacy. EC16-1/saporin, at nanomolar concentrations, significantly inhibited the cellular proliferation of parental and ABCB1- and ABCG2-overexpressing cancer cells. EC16-1/saporin did not significantly alter the subcellular localization of ABCB1 and ABCG2. In addition, EC16-1/saporin induced apoptosis in parental and ABCB1- and ABCG2-overexpressing cancer cells. In a murine model system, EC16-1/saporin significantly inhibited the tumor growth in mice xenografted with parental and ABCB1- and ABCG2-overexpressing cancer cells. Our findings suggest that the EC16-1/saporin combination could potentially be a novel therapeutic treatment in patients with parental or ABCB1- and ABCG2-positive drug-resistant cancers.
Living in autistic bodies: bloggers discuss movement control and arousal regulation

Abstract Aim We sought to deepen understanding of embodied experiences of autism by examining how autistic bloggers describe and discuss autism. Methods Working within a qualitative description approach, we sampled 40 blogs written by people who identify as autistic. We conducted a directed content analysis, applying a codebook that was generated using themes from a previous study, while remaining open to additional theme generation and elimination. Results The rich description in the blog posts support our previous finding that autism is a highly embodied experience including challenges with movement control. Additionally, we found arousal regulation (ability to maintain a calm yet alert state) to be an important embodied experience for the bloggers. Conclusions Our findings support a conceptualization of autism that sees embodiment, movement and arousal regulation as important elements of autism. Rehabilitation researchers and professionals should note that autistic insider perspectives can and must be accessed for optimal outcomes. IMPLICATIONS FOR REHABILITATION Clinicians should consider movement control (starting and stopping movement at will) difficulties as possible barriers to function for some autistic people. Clinicians should consider arousal regulation (ability to govern physiological and psychological activation level) difficulties as a possible barrier to function for some autistic people. Clinicians should be cautious when interpreting observed behaviours of autistic people and should make every effort to get explanations for behaviour directly from the perspective of individual clients.
HIV-1 Nef counteracts autophagy restriction by enhancing the association between BECN1 and its inhibitor BCL2 in a PRKN-dependent manner

ABSTRACT Macroautophagy/autophagy is an auto-digestive pro-survival pathway activated in response to stress to target cargo for lysosomal degradation. In recent years, autophagy has become prominent as an innate antiviral defense mechanism through multiple processes, such as targeting virions and viral components for elimination. These exciting findings have encouraged studies on the ability of autophagy to restrict HIV. However, the role of autophagy in HIV infection remains unclear. Whereas some reports indicate that autophagy is detrimental for HIV, others have claimed that HIV deliberately activates this pathway to increase its infectivity. Moreover, these contrasting findings seem to depend on the cell type investigated. Here, we show that autophagy poses a hurdle for HIV replication, significantly reducing virion production. However, HIV-1 uses its accessory protein Nef to counteract this restriction. Previous studies have indicated that Nef affects autophagy maturation by preventing the fusion between autophagosomes and lysosomes. Here, we uncover that Nef additionally blocks autophagy initiation by enhancing the association between BECN1 and its inhibitor BCL2, and this activity depends on the cellular E3 ligase PRKN. Remarkably, the ability of Nef to counteract the autophagy block is more frequently observed in pandemic HIV-1 and its simian precursor SIVcpz infecting chimpanzees than in HIV-2 and its precursor SIVsmm infecting sooty mangabeys. In summary, our findings demonstrate that HIV-1 is susceptible to autophagy restriction and define Nef as the primary autophagy antagonist of this antiviral process. Abbreviations: 3-MA: 3-methyladenine; ACTB: actin, beta; ATG16L1: autophagy related 16 like 1; BCL2: bcl2 apoptosis regulator; BECN1: beclin 1; cDNA: complementary DNA; EGFP: enhanced green fluorescence protein; ER: endoplasmic reticulum; Gag/p55: group-specific antigen; GFP: green fluorescence protein; GST: glutathione S transferase; HA: hemagglutinin; HIV: human immunodeficiency virus; IP: immunoprecipitation; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Nef: negative factor; PRKN: parkin RBR E3 ubiquitin ligase; PtdIns3K: phosphatidylinositol 3 kinase; PtdIns3P: phosphatidylinositol 3 phosphate; PTM: post-translational modification; RT-qPCR: reverse transcription followed by quantitative PCR; RUBCN: rubicon autophagy regulator; SEM: standard error of the mean; SERINC3: serine incorporator 3; SERINC5: serine incorporator 5; SIV: simian immunodeficiency virus; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; UVRAG: UV radiation resistance associated gene; VSV: vesicular stomatitis virus; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1.
Composite Uremic Load and Physical Performance in Hemodialysis Patients: A Cross-Sectional Study

Impaired physical performance is common in patients on hemodialysis (HD) and is associated with poor prognosis. A patient relevant marker of adequacy of dialysis is lacking. Previous studies evaluated uremic toxicity by assessing the impact of different uremic toxins separately. However, such an approach is most likely not reflective of true uremic toxicity. Therefore, this cross-sectional study aimed to examine if the uremic syndrome, estimated as one composite of different uremic toxins (facilitated by ridge regression method) to reflect the kinetic behavior during dialysis, is associated with physical performance in patients on HD. Levels of p-cresyl glucuronide and sulfate, indole-acetic acid, indoxyl sulfate, uric acid, hippuric acid, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were assessed and associated by ridge regression to muscle strength, functional exercise capacity, and measures of balance and coordination. 75 HD patients were included (mean age 68 years, 57% male). The composite of different uremic toxins (i.e., uremic load) explained 22% of the variance in handgrip strength. Although there was an association between full body muscle strength and the composite uremic load independent of nutritional status, age and gender, the predictive power of composite uremic load for muscle weakness is limited. Single uremic toxins as well as composite uremic load were not associated with exercise capacity, coordination, and balance, indicating that the degree of uremia does not predict physical performance in patients on HD.
A DYNAMIC LONGITUDINAL MODELLING APPROACH FOR THE RELATIONSHIP BETWEEN THE HUMAN CAPITAL OF BOARD DIRECTORS AND FIRM FINANCIAL PERFORMANCE

This paper investigates the effect the human capital of directors on the financial performance of Vietnamese listed companies. The dynamic system generalized method of moments (system GMM) estimator is used to examine a panel dataset consisting of 315 observations over a four-year period from 2008 to 2011. In line with the resource dependence theory, we report that the human capital of directors appears to have a positive influence upon the firm financial performance. To the best of our knowledge, this study is the pioneering work on the topic of human capital of directors and firm performance for the publicly listed companies in Vietnam. This study, by applying a dynamic longitudinal modelling approach, extends the nascent literature on board human capital as well as more generally to the corporate governance literature by providing robust empirical evidence showing that the general human capital of board directors may add value to firms. Our finding, therefore, supports the efforts made by the Vietnamese policy makers in setting up qualification standards as well as skill diversity for the boards.
International Journal of Management Sciences and Business Research, Jan-2020 ISSN (2226-8235) Vol-9, Issue 1

The study sought to investigate the effect of job satisfaction on employees’ productivity in selected oil and gas servicing companies in Lagos State, Nigeria. Despite the perception of the oil sector is the mainstream of income to foreign reserve, and generating highly satisfying source of employment to the populace, a steady decline in the performance of the sector has been observed, leading to the collapse of various oil and gas servicing companies, massive retrenchment of workers, non-payment of salaries, inflation, high cost of living, and high exchange rate. A cross-sectional survey of 421 employees was carried out using a validated instrument and achieved an 83% response rate. The findings showed that job satisfaction has a positive and significant effect on employees’ productivity of the selected oil and gas firms in Lagos state, Nigeria. The study therefore recommends that oil and gas firms must continue to strive to keep workers satisfied through improved pay, better working conditions, job security in order to enhance employees’ productivity.
YIELD, MORPHOLOGICAL CHARACTERISTICS AND NUTRITIONAL VALUE OF NEW PSEUDOSTEM – TYPE CULTIVARS OF JAPANESE BUNCHING ONION

In cultivation of Japanese bunching onion as an annual crop harvested for bunches there is required to use pseudostem – type cultivars, with high rate of growth, rich in valuable phytochemicals. In a field study there was evaluated the yield potential, quality of the crop and nutritional value of the following pseudostem – type cultivars: Sprintesa, Parade, Performer, Ishikura Long White, Red Toga, Freedy and Totem. Kroll cultivar commonly recommended as a perennial crop grown for the use of cut foliage was recognized as the control. Seedlings produced in multicell trays were transplanted into the field on 19–22 April and harvested on 19–25 June, when majority of plants reached the pseudostem diameter > 10 mm. At harvest there were evaluated the yield size, morphological features of plants and content selected organic and mineral compounds. Most of the exammed cultivars appeared to be suitable for early spring growing for bunches, among which Parade produced the highest marketable yield and beside Sprintesa characterized the longest pseudostem as well as low nitrates content. ‘Kroll’ grown as annual crop for bunches produced yield similar to ‘Red Toga’ and ‘Freedy’, while significantly lower to the other examined cultivars. Its plants characterized by low mean weight and short pseudostem, but high amounts of potassium and low nitrates accumulation.
Learning Relaxed Belady for Content Distribution Network Caching

This paper presents a new approach for caching in CDNs that uses machine learning to approximate the Belady MIN (oracle) algorithm. To accomplish this complex task, we propose a CDN cache design called Learning Relaxed Belady (LRB) to mimic a Relaxed Belady algorithm, using the concept of Belady boundary. We also propose a metric called good decision ratio to help us make better design decisions. In addition, the paper addresses several challenges to build an end-to-end machine learning caching prototype, including how to gather training data, limit memory overhead, and have lightweight training and prediction. We have implemented an LRB simulator and a prototype within Apache Traffic Server. Our simulation results with 6 production CDN traces show that LRB reduces WAN traffic compared to a typical production CDN cache design by 4– 25%, and consistently outperform other state-of-the-art methods. Our evaluation of the LRB prototype shows its overhead is modest and it can be deployed on today’s CDN servers.
Promoting a balanced early years curriculum for young children with vision impairment: Developing and sustaining personal agency through a bioecological systems perspective

Through the use of their developing vision, young children develop increasingly sophisticated ways of establishing control within different learning environments, thereby helping them to exert influence as active ‘agents’. Vision impairment can present significant barriers to a child developing personal agency through reducing access to visual information. In this article, we present the parameters of a conceptual framework to inform the design of intervention approaches that can help to reduce these barriers. We draw on a dual model of ‘access’, contextualised within a bioecological systems perspective, to examine how young children with vision impairment can establish increasing personal agency through intervention approaches that promote progressive independence access skills within an ‘ethos of empowerment’. In presenting new conceptual foundations for examining the development of personal agency in young children with vision impairment, the article has significance for research, policy, and practice in vision impairment education and offers a theoretical reference point for related areas of early childhood inclusive education.
Results of the Local Steroid Injections in the Simple Bone Cyst

Yöntemler: BKK saptanan 17 hasta (11 erkek, 6 kız ; ortalama yaş 12,4 yıl; dağılım 2-39 yıl) iki iğne tekniği kullanılarak kist içine metilprednizolon asetat (MPA) enjeksiyonuyla tedavi edildi. Kist altı olguda humerus proksimaline, iki olguda kalkaneusa (olgulardan biri bilateral), yedi olguda proksimal femura ve iki olguda da tibiaya yerleşmişti. Üç hastada steroid enjeksiyonu öncesinde patolojik kırık oluşmuştu. Patolojik kırığı olan bu üç hastaya kırıkları iyileştikten sonra MPA enjeksiyonu yapıldı. Hastalara sekiz hafta arayla, herbiri 40-160 mg MPA içeren en fazla dört enjeksiyon uygulandı. Hastalar enjeksiyon sonrasında birinci, üçüncü, altıncı aylarda ve birinci yılda çekilen direkt grafiler ile takip edildi. İlk yıldan sonra hastalar yılda bir kez düz grafilerle takibe alındı. Hastaların ortalama takip süresi 22 ay (dağılım=3-48 ay) idi. Kist iyileşmesi modifiye Neer sınıflandırmasına göre değerlendirildi.
Automating Time-series Safety Analysis for Automotive Control Systems Using Weighted Partial Max-SMT

: We propose a method to automate the detection of signal disturbance for a given unsafe property. To incorporate a signal disturbance, we introduce an auxiliary variable, called a cushion variable , for each signal variable to store a value altered by the disturbance that causes unintended state transitions. The signal disturbance is deﬁned to negate the equalities between signal variables and their cushion variables. We develop a method to e ﬃ ciently detect the signal disturbance by using a weighted partial maximum satisﬁability modulo theories (Max-SMT) technique as a set of variables altered by faults resulting in an undesirable condition. By assigning the weights properly to the equations, we control the derivation of signal disturbance patterns with the required property. We present an experimental application of our method to a simpliﬁed cruise control system as a practical case study in two well-known methods of safety analysis, namely system theoretic process analysis (STPA) and fault tree analysis (FTA), for the automatic detection of time-series signal disturbances.
Camera-Geometry Interpenetration in Virtual Reality

One of the most signiﬁcant challenges facing virtual reality experiences is the virtual world being misaligned from the real-world environment. This makes problems arise if a user ventures too far outward - if the virtual world is larger, then the user is at risk of running into walls in the real world, and, conversely, if the real world is larger, the user is at risk of running through virtual walls. In this study, we examined the second case to ﬁgure out the best practice for handling such scenarios. After reviewing how commercial experiences handle these events, we implemented ten techniques. We then conducted a user study, grading each method on comfort, intuitiveness, and immersion. We present results that provide strong evidence for a blend of a few techniques, none of which are yet popularly employed by commercial games.
Phytosociology, ecology and conservation status of Carlina acanthifolia subsp. utzka on its northern distribution limit (Poland and Ukraine)

This paper is focused on phytosociological and ecological peculiarities of the vulnerable species Carlina acanthifolia subsp. utzka in Ukraine and Poland at the northern distribution limit of the species. Based on the analysis of 86 relevés, we recognised three associations within Festuco-Brometea class in which Carlina acanthifolia subsp. utzka occurs. We also revealed an ecological differencies between habitats of the species using Didukh’s phytoindication scale. It was concluded that the limited factors of Carlina acanthifolia subsp. utzka distribution are soil humidity, carbonate content and thermal climate. The assessment of ecological amplitude of Carlina acanthifolia subsp. utzka shows that the most vulnerable are the habitats in the Southern Podillia (Ukraine), at the eastern limit of the total range. It has been revised the carbonate content indices for Carlina acanthifolia subsp. utzka species and has been proposed new ecological amplitude according to our results. We propose to restore the C. acanthifolia subsp. utzka habitats using grassland management measures within Emerald and Natura 2000 sites.
Improving Implicit Recommender Systems with Auxiliary Data

Most existing recommender systems leverage the primary feedback only, despite the fact that users also generate a large amount of auxiliary feedback. These feedback usually indicate different user preferences when comparing to the primary feedback directly used to optimize the system performance. For example, in E-commerce sites, view data is easily accessible, which provides a valuable yet weaker signal than the primary feedback of purchase. In this work, we improve implicit feedback-based recommender systems (dubbed Implicit Recommender Systems) by integrating auxiliary view data into matrix factorization (MF). To exploit different preference levels, we propose both pointwise and pairwise models in terms of how to leverage users’ viewing behaviors. The latter model learns the pairwise ranking relations among purchased, viewed, and non-viewed interactions, being more effective and flexible than the former pointwise MF method. However, such a pairwise formulation poses a computational efficiency problem in learning the model. To address this problem, we design a new learning algorithm based on the element-wise Alternating Least Squares (eALS) learner. Notably, our designed algorithm can efficiently learn model parameters from the whole user-item matrix (including all missing data), with a rather low time complexity that is dependent on the observed data only. Extensive experiments on two real-world datasets demonstrate that our method outperforms several state-of-the-art MF methods by 6.43%∼ 6.75%. Our implementation is available at https://github.com/dingjingtao/Auxiliary_enhanced_ALS.
Antimicrobial resistance in aquaculture: a crisis for concern

Emergence of antimicrobial resistance (AMR) in cultured fishes is one of the major challenges faced in aquaculture. The high prevalence of bacterial infections in fishes leads to frequent use of antibiotics and thus their persistence in the aquatic environment, which in turn results in the proliferation of antibiotic resistant bacteria. The AMR in aquaculture can be transferred to clinically important strains of natural environment through horizontal gene transfer, thereby affecting the whole ecosystem. Most of the cultured fishes, including ornamental possess diverse pathogens exhibiting multiple antibiotic resistance. A thorough understanding of the gene transfer systems such as plasmids, transposons, integrons and gene cassettes can unravel the complexity of antimicrobial resistance in aquaculture. Continuous monitoring programmes, timely detections of the resistant bacteria and implementation of proper regulations are necessary to curb the dissemination of AMR in aquaculture. The present review summarises the antimicrobial use and AMR in cultured fishes, genetic mechanisms involved in the development of resistance, and the management strategies to restrict the spread of AMR in aquaculture.
Factors Affecting the Efficacy, Tolerability and Compliance of Dietary Therapy for Epilepsy- Four-Years Experience

Objective: To evaluate the clinical effectiveness of the Ketogenic Diet (KD) in children as measured by: seizure reduction rates, patient side effects, patient tolerance, and compliance of 2 forms of the KD, the classical and modified Atkins KDs (MAKD). Study Design: A single-centre, retrospective study of 43 children with Intractable Epilepsy (IE) commencing the KD between 2012 and 2015. We assessed patient demographics, history of epilepsy, nutritional management, side effects of the KD, growth parameters and biochemistry records. Compliance and tolerance of the KD were explored by recording reasons for modification and cessation. Results: The median age at initiation was 3 years 10 months (range 4 months to 12 years), and the median duration of therapy was 1 year and 4 months. Twenty-five of 43 children (58%) had epileptic encephalopathies. Thirty-five (81%), 26 (60%) and 18 (42%) of children remained on the diet at 3, 12 and 24 months. Of those, 7 (16%), 4 (9%) and 5 (12%) achieved seizure freedom, and 20 (47%), 15 (35%) and 10 (23%) patients achieved >50% reduction in seizures at 3, 12 and 24 months respectively. Seizure reduction was significantly associated with diet duration (p<0.005), and reduction in anti-epileptic medications (p<0.005). Reasons for diet discontinuation included no improvement in seizures (26%), poor compliance (9%), adverse effects (9%) and weight loss (9%). Conclusion: The classical KD and MAKD provide comparable seizure control, seizure freedom and reduction in medication, particularly for those who commit to remaining on the KD out to 24 months.