Miracle-dz/UniFAR-FTUs huggingface dataset:
A Combined Acceptor Photobleaching and Donor Fluorescence Lifetime Imaging Microscopy Approach to Analyze Multi-Protein Interactions in Living Cells

Protein–protein interaction studies often provide new insights, i.e., into the formation of protein complexes relevant for structural oligomerization, regulation of enzymatic activity or information transfer within signal transduction pathways. Mostly, biochemical approaches have been used to study such interactions, but their results are limited to observations from lysed cells. A powerful tool for the non-invasive investigation of protein–protein interactions in the context of living cells is the microscopic analysis of Förster Resonance Energy Transfer (FRET) among fluorescent proteins. Normally, FRET is used to monitor the interaction state of two proteins, but in addition, FRET studies have been used to investigate three or more interacting proteins at the same time. Here we describe a fluorescence microscopy-based method which applies a novel 2-step acceptor photobleaching protocol to discriminate between non-interacting, dimeric interacting and trimeric interacting states within a three-fluorophore setup. For this purpose, intensity- and fluorescence lifetime-related FRET effects were analyzed on representative fluorescent dimeric and trimeric FRET-constructs expressed in the cytosol of HEK293 cells. In particular, by combining FLIM- and intensity-based FRET data acquisition and interpretation, our method allows to distinguish trimeric from different types of dimeric (single-, double- or triple-dimeric) protein–protein interactions of three potential interaction partners in the physiological setting of living cells.
Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

Rationale Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited. Objectives To evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome. Methods Paired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured. Measurements and Main Results In all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined. Conclusions Critically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory “storm” in severe COVID-19.
Severe Dementia Predicts Weight Loss by the Time of Death

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination. Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables. Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5–24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: β = −1.92, 95% CI = −3.77 to −0.06, p = 0.042; severe: β = −2.91, 95% CI = −3.97 to −1.86, p < 0.001). Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages.
Comparative Neurology of Circadian Photoreception: The Retinohypothalamic Tract (RHT) in Sighted and Naturally Blind Mammals

The mammalian eye contains two systems for light perception: an image detecting system constituted primarily of the classical photoreceptors, rods and cones, and a non-image forming system (NIF) constituted of a small group of intrinsically photosensitive retinal ganglion cells driven by melanopsin (mRGCs). The mRGCs receive input from the outer retina and NIF mediates light entrainment of circadian rhythms, masking behavior, light induced inhibition of nocturnal melatonin secretion, pupillary reflex (PLR), and affect the sleep/wake cycle. This review focuses on the mammalian NIF and its anatomy in the eye as well as its neuronal projection to the brain. This pathway is known as the retinohypothalamic tract (RHT). The development and functions of the NIF as well as the knowledge gained from studying gene modified mice is highlighted. Furthermore, the similarities of the NIF between sighted (nocturnal and diurnal rodent species, monkeys, humans) and naturally blind mammals (blind mole rats Spalax ehrenbergi and the Iberian mole, Talpa occidentalis) are discussed in relation to a changing world where increasing exposure to artificial light at night (ALAN) is becoming a challenge for humans and animals in the modern society.
Hyper-Reactivity to Salience Limits Social Interaction Among Infants Born Pre-term and Infant Siblings of Children With ASD

The ability to engage attention with selected stimuli is essential for infants to explore the world and process information relating to their surroundings. There are two main populations with a higher risk to develop attentional and social deficits whose deficits may arise from difficulties in regulating attention to salient cues: (1) siblings of children diagnosed with Autism; and (2) infants who were born pre-term. This study investigated infants' (N = 97) attention-engagement and pupil-dilation (PD) at 9 months of age, using a gaze-contingent paradigm and a structured social interaction. Specifically, we explored attention to stimuli with simple salient features (e.g., clear defined shapes, colors, and motions) vs. more complex non-social cues (amorphous shapes, colors, and motions) and social interaction in typically developing infants (TD, N = 25) and among two groups of infants at-risk to develop social difficulties (pre-terms, N = 56; siblings of children with Autism, N = 16). Findings show that the two risk groups preferred stimuli with simple features (F = 11.306, p < 0.001), accompanied by increased PD (F = 6.6, p < 0.001). Specifically, pre-term infants showed increased PD toward simple vs. complex stimuli (p < 0.001), while siblings showed a pervasive hyper-arousal to both simple and complex stimuli. Infants in the TD group preferred complex stimuli with no change in PD. Finally, the preference for the simple stimulus mediated the relationship between increased risk for social difficulties and decreased engagement duration in face-to-face interaction with the experimenter. Results suggest that activation of the attention-salience network shapes social abilities at infancy. Further, hyper-reactivity to salient stimuli limits social interaction among infants born pre-term and siblings of children with ASD.
Effect of Nitrogen Addition on Selection of Germination Trait in an Alpine Meadow on the Tibet Plateau

Seed germination requirements may determine the kinds of habitat in which plants can survive. We tested the hypothesis that nitrogen (N) addition can change seed germination trait-environmental filter interactions and ultimately redistribute seed germination traits in alpine meadows. We determined the role of N addition on germination trait selection in an alpine meadow after N addition by combining a 3-year N addition experiment in an alpine meadow and laboratory germination experiments. At the species level, germination percentage, germination rate (speed) and breadth of temperature niche for germination (BTN) were positively related to survival of a species in the fertilized community. In addition, community-weighted means of germination percentage, germination rate, germination response to alternating temperature and BTN increased. However, germination response to wet-cold storage (cold stratification) and functional richness of germination traits was lower in alpine meadows with high-nitrogen addition than in those with no, low and medium N addition. Thus, N addition had a significant influence on environmental filter-germination trait interactions and generated a different set of germination traits in the alpine meadow. Further, the effect of N addition on germination trait selection by environmental filters was amount-dependent. Low and medium levels of N addition had less effect on redistribution of germination traits than the high level.
The Importance of Being in Touch

This paper describes a series of studies resulting from the finding that when free floating in weightless conditions with eyes closed, all sense of one's spatial orientation with respect to the aircraft can be lost. But, a touch of the hand to the enclosure restores the sense of spatial anchoring within the environment. This observation led to the exploration of how light touch of the hand can stabilize postural control on Earth even in individuals lacking vestibular function, and can override the effect of otherwise destabilizing tonic vibration reflexes in leg muscles. Such haptic stabilization appears to represent a long loop cortical reflex with contact cues at the hand phase leading EMG activity in leg muscles, which change the center of pressure at the feet to counteract body sway. Experiments on dynamic control of balance in a device programmed to exhibit inverted pendulum behavior about different axes and planes of rotation revealed that the direction of gravity not the direction of balance influences the perceived upright. Active control does not improve the accuracy of indicating the upright vs. passive exposure. In the absence of position dependent gravity shear forces on the otolith organs and body surface, drifting and loss of control soon result and subjects are unaware of their ongoing spatial position. There is a failure of dynamic path integration of the semicircular canal signals, such as occurs in weightless conditions.
(Sympathy for) the Devil You Know: Openness, Psychological Entropy, and the Case of the Incumbency Advantage

Why do some individuals prefer lesser-known, riskier experiences over more well-known options in life? In this paper, we focus on the case of the electoral advantage to incumbency, and the role that psychological entropy reduction can play in undermining that advantage among individuals who lack simplifying heuristics, such as party brand loyalty. We build on recent work in political psychology, applying a more general political psychology framework linking the Big Five personality trait of Openness to a compulsion to gather and process information. Using data from the 2014 and 2016 Cooperative Congressional Election Studies, we find more Open respondents are more willing to vote for more uncertain House challengers at higher rates, but only among Independent respondents who are unable to rely on partisan cues to simplify the psychological entropy presented by such challengers. This suggests Openness captures relative preferences for encountering and reducing psychological entropy rather than traditionally defined risk preferences.
Genome-Wide Association Study for Grain Micronutrient Concentrations in Wheat Advanced Lines Derived From Wild Emmer

Wheat is one of the important staple crops as the resources of both food and micronutrient for most people of the world. However, the levels of micronutrients (especially Fe and Zn) in common wheat are inherently low. Biofortification is an effective way to increase the micronutrient concentration of wheat. Wild emmer wheat (Triticum turgidum ssp. dicoccoides, AABB, 2n = 4x = 28) is an important germplasm resource for wheat micronutrients improvement. In the present study, a genome-wide association study (GWAS) was performed to characterize grain iron, zinc, and manganese concentration (GFeC, GZnC, and GMnC) in 161 advanced lines derived from wild emmer. Using both the general linear model and mixed linear model, we identified 14 high-confidence significant marker-trait associations (MTAs) that were associated with GFeC, GZnC, and GMnC of which nine MTAs were novel. Six MTAs distributed on chromosomes 3B, 4A, 4B, 5A, and 7B were significantly associated with GFeC. Three MTAs on 1A and 2A were significantly associated with GZnC and five MTAs on 1B were significantly associated with GMnC. These MTAs show no negative effects on thousand kernel weight (TKW), implying the potential value for simultaneous improvement of micronutrient concentrations and TKW in breeding. Meanwhile, the GFeC, GZnC and GMnC are positively correlated, suggesting that these traits could be simultaneously improved. Genotypes containing high-confidence MTAs and 61 top genotypes with a higher concentration of grain micronutrients were recommended for wheat biofortification breeding. A total of 38 candidate genes related to micronutrient concentrations were identified. These candidates can be classified into four main groups: enzymes, transporter proteins, MYB transcription factor, and plant defense responses proteins. The MTAs and associated candidate genes provide essential information for wheat biofortification breeding through marker-assisted selection (MAS).
Mortality Rate and Characteristics of Deaths Following COVID-19 Vaccination

Background: The emergency use authorization for coronavirus disease 2019 (COVID-19) vaccines brought both hopes and concerns to the Americans and others. We aimed to estimate the mortality rate of COVID-19 vaccination and presented characteristics of deaths following COVID-19 vaccination. Methods: Data on deaths following COVID-19 vaccination were obtained from the Vaccine Adverse Event Reporting System (VAERS) from December 11, 2020 through January 8, 2021. The Centers for Disease Control and Prevention (CDC) COVID Data Tracker was used to identify the total number of people receiving COVID-19 vaccines during the same period to estimate the mortality rate. Stratified analysis was conducted by the location of vaccination. Results: As of January 8, 2021, 55 deaths were reported, and the mortality rate of COVID-19 vaccination was 8.2 per million population. A total of 37 deaths were reported among long-term care facility residents, and the mortality rate was 53.4 per million population. Top reported comorbidities associated with deaths included hypertension, dementia, chronic obstructive pulmonary disease (COPD), diabetes, and heart failure. In addition, dementia was more likely to be associated with deaths vaccinated at long-term care facilities than at other locations. Conclusion: The benefits of COVID-19 vaccines outweigh the potential risks in older frail populations, and our findings do not support actions to exclude older adults from being vaccinated. However, continued monitoring of COVID-19 vaccination is still warranted.
Development and Characterization of PLGA Nanoparticles Containing 17-DMAG, an Hsp90 Inhibitor

Leishmaniasis is a spectrum of neglected tropical diseases and its cutaneous form (CL) is characterized by papillary or ulcerated skin lesions that negatively impact patients' quality of life. Current CL treatments suffer limitations, such as severe side effects and high cost, making the search for new therapeutic alternatives an imperative. In this context, heat shock protein 90 (Hsp90) could present a novel therapeutic target, as evidence suggests that Hsp90 inhibitors, such as 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG), may represent promising chemotherapeutic agents against CL. As innovative input for formulation development of 17-DMAG, nano-based drug delivery systems could provide controlled release, targeting properties, and reduced drug toxicity. In this work, a double emulsion method was used to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing 17-DMAG. The nanoparticle was developed using two distinct protocols: Protocol 1 (P1) and Protocol 2 (P2), which differed concerning the organic solvent (acetone or dichloromethane, respectively) and procedure used to form double-emulsions (Ultra-Turrax® homogenization or sonication, respectively). The nanoparticles produced by P2 were comparatively smaller (305.5 vs. 489.0 nm) and more homogeneous polydispersion index (PdI) (0.129 vs. 0.33) than the ones made by P1. Afterward, the P2 was optimized and the best composition consisted of 2 mg of 17-DMAG, 100 mg of PLGA, 5% of polyethylene glycol (PEG 8000), 1.5 mL of the internal aqueous phase, 1% of polyvinyl alcohol (PVA), and 4 mL of the organic phase. Optimized P2 nanoparticles had a particle size of 297.2 nm (288.6–304.1) and encapsulation efficacy of 19.35% (15.42–42.18) by the supernatant method and 31.60% (19.9–48.79) by the filter/column method. Release kinetics performed at 37°C indicated that ~16% of the encapsulated 17-DMAG was released about to 72 h. In a separate set of experiments, a cell uptake assay employing confocal fluorescence microscopy revealed the internalization by macrophages of P2-optimized rhodamine B labeled nanoparticles at 30 min, 1, 2, 4, 6, 24, 48, and 72 h. Collectively, our results indicate the superior performance of P2 concerning the parameters used to assess nanoparticle development. Therefore, these findings warrant further research to evaluate optimized 17-DMAG-loaded nanoparticles (NP2-17-DMAG) for toxicity and antileishmanial effects in vitro and in vivo.
PROPOSED FRAMEWORK FOR IMPROVING PERFORMANCE OF FAMILIAL CLASSIFICATION IN ANDROID MALWARE

Because of the recent developments in hardware and software technologies for mobile phones, people depend on their smartphones more than ever before. Today, people conduct a variety of business, health, and financial transactions on their mobile devices. This trend has caused an influx of mobile applications that require users' sensitive information. As these applications increase so too have the number of malicious applications increased, which may compromise users' sensitive information. Between all smartphone, Android receives major attention from security practitioners and researchers due to the large number of malicious applications. For the past twelve years, Android malicious applications have been clustered into groups for better identification. Characterizing the malware families can improve the detection process and understand the malware patterns. However, in the research community, detecting new malware families is a challenge. In this research, a framework is proposed to improve the performance of familial classification in Android malware. The framework is named a Reverse Engineering Framework (RevEng). Within RevEng, applications' permissions were selected and then fed into machine learning algorithms. Through our research, we created a reduced set of permissions using Extremely Randomized Trees algorithm that achieved high accuracy and a
Graph-based Interactive Data Federation System for Heterogeneous Data Retrieval and Analytics

Given the increasing number of heterogeneous data stored in relational databases, file systems or cloud environment, it needs to be easily accessed and semantically connected for further data analytic. The potential of data federation is largely untapped, this paper presents an interactive data federation system (https://vimeo.com/319473546) by applying large-scale techniques including heterogeneous data federation, natural language processing, association rules and semantic web to perform data retrieval and analytics on social network data. The system first creates a Virtual Database (VDB) to virtually integrate data from multiple data sources. Next, a RDF generator is built to unify data, together with SPARQL queries, to support semantic data search over the processed text data by natural language processing (NLP). Association rule analysis is used to discover the patterns and recognize the most important co-occurrences of variables from multiple data sources. The system demonstrates how it facilitates interactive data analytic towards different application scenarios (e.g., sentiment analysis, privacy-concern analysis, community detection).
Condensed Matter and Interphases

A new principle for supplying volatile precursors to MOCVD gas-phase chemical deposition systems is proposed, based on a two-stage evaporation of an organic solution of precursors from a soaked cotton thread, which passes sequentially through the zones of evaporation of the solvent and precursors. The technological capabilities of TSF-MOCVD (Thread-Solution Feed MOCVD) are demonstrated based on examples of obtaining thin epitaxial films of СеО2, h-LuFeO3 and thin-film heterostructures β-Fe2O3/h-LuFeO3. The results of studying the obtained films by X-ray diffraction, energy dispersive X-ray analysis, and highand low-resolution transmission microscopy are presented. Using the TSF module, one can finely vary the crystallisation conditions, obtaining coatings of the required degree of crystallinity, as evidenced by the obtained dependences of the integral width of the h-LuFeO3 reflection on the film growth rate. Based on the TEM and XRD data, it was concluded that β-Fe2O3 grows epitaxially over the h-LuFeO3 layer. Thus, using TSF-MOCVD, one can flexibly change the composition of layered heterostructures and obtain highly crystalline epitaxial films with a clear interface in a continuous deposition process.
Earnings Quality and Income Smoothing Motives: Evidence from Indonesia

Earnings management is very important for companies that aim for decision-making. The research was conducted to analyze the quality of earnings and income smoothing motives in manufacturing companies in Indonesia. The research approach is carried out with a quantitative approach. The sampling method using purposive sampling was associated with several criteria so that a sample of 130 was determined, which was analyzed during the 4 years of the study. The partial least square method was used for data analysis. The results of the study state that institutional ownership has no effect on earnings quality, institutional ownership has a negative effect on income smoothing, leverage has a negative effect on income smoothing, independent commissioners have a positive effect on earnings quality as well as independent commissioners have a positive effect on income smoothing. We assume that the tendency of income smoothing can affect the quality of efficient earnings. Meanwhile, income smoothing affects the quality of company earnings. Management that performs income smoothing is more aimed at conveying the company’s prospects for generating profits rather than opportunistic motives.