Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis and Biological Evaluation of New Ligustrazine Derivatives as Anti-Tumor Agents

To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the “combination principle” in drug discovery. The ligustrazine derivatives’ anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 α,12 α-dihydroxy-5β-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD50 value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.
Peak Ground Displacement Saturates Exactly When Expected: Implications for Earthquake Early Warning

The scaling of rupture properties with magnitude is of critical importance to earthquake early warning systems that rely on source characterization using limited snapshots of waveform data. ShakeAlert, a prototype earthquake early warning system that is being developed for the western United States, provides real‐time estimates of earthquake magnitude based on P wave peak ground displacements measured at stations triggered by the event. The algorithms used in ShakeAlert assume that the displacement measurements at each station are statistically independent and that there exists a linear and time‐independent relation between log peak ground displacement and earthquake magnitude. Here we challenge this basic assumption using the largest data set assembled for this purpose to date: a comprehensive database of more than 140,000 vertical‐component waveforms from M4.5 to M9 earthquakes occurring near Japan from 1997 through 2018 and recorded by the K‐NET and KiK‐net strong‐motion networks. By analyzing the time evolution of P wave peak ground displacements for these earthquakes, we show that there is a break, or saturation, in the magnitude‐displacement scaling that depends on the length of the measurement time window. We demonstrate that the magnitude at which this saturation occurs is well‐explained by a simple and nondeterministic model of earthquake rupture growth. We then use the predictions of this saturation model to develop a Bayesian framework for estimating posterior uncertainties in real‐time magnitude estimates.
Prophylactic immunotherapy of Alzheimer's disease using recombinant amyloid-β B-cell epitope chimeric protein as subunit vaccine

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. The neuropathological features of the disease include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuronal loss in affected brain regions. The amyloid cascade hypothesis suggests that production and accumulation of excessive amyloid-β (Aβ) may be the main cause in the onset and progression of Alzheimer's disease. Active and passive immunotherapy targeting Aβ may be the most promising strategy to prevent or treat AD. This commentary focuses on the prophylactic immunotherapy of Alzheimer's disease using recombinant Aβ B-cell epitope chimeric protein as subunit vaccine targeting amyloid-β. We discuss the efficiency and perspective of this type of recombinant subunit protein vaccine and suggest a novel direction on the path to a successful AD immunotherapy. This novel chimeric protein immunogen as subunit vaccine of AD may be designed to mimic the assembly states of Aβ42 or oligomers using multivalent foldable Aβ1–15 (B cell epitopes of Aβ42) and foreign T helper (Th) epitopes (as the T cell epitopes of Aβ42) constructs.
A chimerical phagocytosis model reveals the recruitment by Sertoli cells of autophagy for the degradation of ingested illegitimate substrates

Phagocytosis and autophagy are typically dedicated to degradation of substrates of extrinsic and intrinsic origins respectively. Although overlaps between phagocytosis and autophagy were reported, the use of autophagy for ingested substrate degradation by nonprofessional phagocytes has not been described. Blood-separated tissues use their tissue-specific nonprofessional phagocytes for homeostatic phagocytosis. In the testis, Sertoli cells phagocytose spermatid residual bodies produced during germ cell differentiation. In the retina, pigmented epithelium phagocytoses shed photoreceptor tips produced during photoreceptor renewal. Spermatid residual bodies and shed photoreceptor tips are phosphatidylserine-exposing substrates. Activation of the tyrosine kinase receptor MERTK, which is implicated in phagocytosis of phosphatidylserine-exposing substrates, is a common feature of Sertoli and retinal pigmented epithelial cell phagocytosis. The major aim of our study was to investigate to what extent phagocytosis by Sertoli cells may be tissue specific. We analyzed in Sertoli cell cultures that were exposed to either spermatid residual bodies (legitimate substrates) or retina photoreceptor outer segments (illegitimate substrates) the course of the main phagocytosis stages. We show that whereas substrate binding and ingestion stages occur similarly for legitimate or illegitimate substrates, the degradation of illegitimate but not of legitimate substrates triggers autophagy as evidenced by the formation of double-membrane wrapping, MAP1LC3A-II/LC3-II clustering, SQSTM1/p62 degradation, and by marked changes in ATG5, ATG9 and BECN1/Beclin 1 protein expression profiles. The recruitment by nonprofessional phagocytes of autophagy for the degradation of ingested cell-derived substrates is a novel feature that may be of major importance for fundamentals of both apoptotic substrate clearance and tissue homeostasis.
Ontology-Based Semantic Information Retrieval Systems in Unstructured P2P Networks

As a revival paradigm for information sharing among distributed nodes in the network, P2P technology can pave the way for decentralized computing and enable more robust e-business applications. Peer-to-peer system is a continuously evolving system consisting of multiple heterogeneous information sources, and a huge number of users with diverse characteristics and needs. Currently, many research projects or practical applications have emerged which only support single keyword search, and few of them support semantic retrieval. In this paper, we propose a model of ontology-based semantic information retrieval systems according to hybrid ontology-based integration approaches, and describe the function of every module. In addition, we briefly discuss some key issues such as query and resource processing, resource searching, ontology mapping. Finally, we conduct a simulation experiment.
Incidence and Player Risk Factors for Injury in Youth Football

ObjectiveTo estimate the incidence of injuries in youth football and to assess the relationship between player-related risk factors (age, body size, biological maturity status) and the occurrence of injury in youth football. DesignProspective over two seasons. SettingTwo communities in central Michigan. ParticipantsSubjects were 678 youth, 9–14 years of age, who were members of 33 youth football teams in two central Michigan communities in the 2000 and 2001 seasons. MethodsCertified athletic trainers (ATCs) were on site to record the number of players at all practices and home games (exposures) and injuries as they occurred. A reportable injury (RI) was defined by the criteria used in the National Athletic Trainers’ Association (NATA) survey of several high school sports. Estimated injury rates (95% confidence intervals) per athlete exposures (AE) and per number of athletes were calculated for practices and games by grade. Player risk factors included age, height, weight, BMI and estimated maturity status. Main Outcome MeasureEstimated injury rates and relative risks of injury during practices and games by grade; logistic regression to evaluate relationships between player-related risk factors and risk of injury. ResultsA total of 259 RIs, 178 in practice and 81 in games, were recorded during the two seasons. Practice injury rates increased with grade level, while game injury rates were similar among fourth through fifth grade and sixth grade players and about twice as high among seventh and eighth grade players. The majority of RIs during the two seasons was minor (64%); the remainder was moderate (18%) and major (13%). Injured fourth through fifth grade players were significantly lighter in weight and had a lower BMI; otherwise, injured and non-injured players within each grade did not differ in age, body size and estimated biological maturity status. Logistic regressions within grade revealed no significant associations between injury and age, height, BMI, and maturity status. ConclusionGame injury rates are higher than practice injury rates, and the incidence of injury tends to increase with grade level. Age, height, BMI and maturity status were not related to the risk of injury in youth football players.
A Four-Dimensional View of IT Business Value

Research on IT business value has recognized that organizational factors play critical roles in affecting how IT impacts on firm performance. However, there is neither a coherent way of specifying organizational factors nor a consensus on the relationship between IT and organizational factors within the research domain. This paper reviews IT business value literature and classifies organizational factors identified in the literature into four categories, based on a four-dimensional view of organizations. A main finding is that pairwise relationships between IT and one single organizational factor have often been the basis for understanding IT business value, while the notion of how IT business value is affected by the interaction between IT and key organizational factors simultaneously is yet to be fully understood and empirically examined. As a result, this paper proposes a holistic approach to understanding IT business value and presents a discussion about future IT business research. Copyright © 2010 John Wiley & Sons, Ltd.
Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis.

BACKGROUND Several trials have addressed the efficacy of liothyronine sodium therapy in euthyroid, nonpsychotic depressed patients refractory to tricyclic antidepressant therapy. We undertook a meta-analysis of these trials. METHODS The MEDLINE database (1966 to May 1995) and published reference lists were examined for controlled clinical trials of triiodothyronine augmentation in euthyroid patients with refractory depression. Quality assessment and data abstraction were performed independently by two reviewers. Results were aggregated three ways: the relative response rate compared with controls, accepting each trial's definition of clinical response; absolute improvement in response rates; and improvements in depression scores, analyzed as continuous variables without a prespecified threshold for clinical response. RESULTS Aggregating eight studies with a total of 292 patients, patients treated with triiodothyronine augmentation were twice as likely to respond as controls (relative response, 2.09; 95% confidence interval [CI], 1.31 to 3.32; P = .002). This corresponded to a 23.2% absolute improvement in response rates (95% CI, 4.5% to 41.9%; P = .02). Improvements in depression scores were moderately large (standardized effect size, 0.62; P < .001). However, study quality was uneven, and results were statistically heterogeneous. Among the four randomized double-blind studies, pooled effects were not significant (relative response, 1.53; 95% CI, 0.70 to 3.35; P = .29), but one study with negative results accounted for most of the intertrial heterogeneity in results. CONCLUSIONS Triiodothyronine augmentation may be an effective empirical method of increasing response rates and decreasing depression severity scores in a subgroup of patients with depression refractory to tricyclic antidepressant therapy, but the total number of patients randomized was small, and additional placebo-controlled data are required for a definitive verdict. Since therapeutic trends now favor other drugs, future trials might usefully examine triiodothyronine augmentation with selective serotonin reuptake inhibitors or compare potentiation strategies, eg, lithium vs triiodothyronine, for managing refractory depression. Such trials would benefit from much larger sample sizes than those reviewed here.
Hunger and Mood during Extended Fasting Are Dependent on the GNB3 C825T Polymorphism

Background/Aims: The 825T allele of the G protein β3-subunit gene (GNB3) is a thrifty genotype associated with an increased risk for obesity. We aimed to determine whether the 825T allele is modifying the subjective response to extended fasting. Methods: We genotyped 108 subjects who underwent an 8-day modified medical fasting treatment [total energy intake <350 kcal (1465 kJ)/day] for the GNB3 C825T polymorphism. Perceived hunger and mood were recorded daily by self-rating visual analogue scales. Results: Whereas weight loss was not dependent on genotype, both mood and hunger were significantly associated with genotype, with homozygous CC genotype carriers having best mood (p = 0.004) and least hunger (p = 0.036) during fasting compared to TT genotype carriers. Conclusions: Pronounced mental discomfort during fasting in 825T allele carriers might partly explain their increased risk for obesity. The strong association between the subjective response to fasting with GNB3 genotypes indicates a role of the gene in the behavioural regulation of food intake, which should be further considered in nutritional intervention studies.
Effects of balancing for physical abilities on player performance, experience and self-esteem in exergames

Game balancing can help players with different skill levels play multiplayer games together; however, little is known about how the balancing approach affects performance, experience, and self-esteem'especially when differences in player strength result from given abilities, rather than learned skill. We explore three balancing approaches in a dance game and show that the explicit approach commonly used in commercial games reduces self-esteem and feelings of relatedness in dyads, whereas hidden balancing improves self-esteem and reduces score differential without affecting game outcome. We apply our results in a second study with dyads where one player had a mobility disability and used a wheelchair. By making motion-based games accessible for people with different physical abilities, and by enabling people with mobility disabilities to compete on a par with able-bodied peers, we show how to provide empowering experiences through enjoyable games that have the potential to increase physical activity and self-esteem.
Metabolic and stress responses of Acinetobacter oleivorans DR1 during long‐chain alkane degradation

Acinetobacter oleivorans DR1 can utilize C12–C30 alkanes as a sole carbon source but not short‐chain alkanes (C6, C10). Two copies of each alkB‐, almA‐ and ladA‐type alkane hydroxylase (AH) are present in the genome of DR1 cells. Expression and mutational analyses of AHs showed that alkB1 and alkB2 are the major AH‐encoding genes under C12–C30, and the roles of other almA‐ and ladA genes are negligible. Our data suggested that AlkB1 is responsible for long‐chain alkane utilization (C24–C26), and AlkB2 is important for medium‐chain alkane (C12–C16) metabolism. Phylogenetic analyses revealed large incongruities between phylogenies of 16S rRNA and each AH gene, which implies that A. oleivorans DR1 has acquired multiple alkane hydroxylases through horizontal gene transfer. Transcriptomic and qRT‐PCR analyses suggested that genes participating in the synthesis of siderophore, trehalose and poly 3‐hydroxybutyrate (PHB) were expressed at much higher levels when cells used C30 than when used succinate as a carbon source. The following biochemical assays supported our gene expression analyses: (i) quantification of siderophore, (ii) measurement of trehalose and (iii) observation of PHB storage. Interestingly, highly induced both ackA gene encoding an acetate kinase A and pta gene encoding a phosphotransacetylase suggested unusual ATP synthesis during C30 alkane degradation, which was demonstrated by ATP measurement using the ΔackA mutant. Impaired growth of the ΔaceA mutant indicated that the glyoxylate shunt pathway is important when C30 alkane is utilized. Our data provide insight into long‐chain alkane degradation in soil microorganisms.
Spontaneous Blink Rates in Children During Different Types of Eye Movements

Abstract: Introduction: The spontaneous blink rate (SBR) is variable in humans. It increases rapidly during childhood before reaching a plateau in adulthood at 10-20 blinks/minute. Our aim was to compare the SBR during different visual tasks in children. Methods: Thirty-nine healthy participants (mean age(SD):13.6(3.5)years, M=21), made horizontal and vertical visually-guided saccades, tracked a horizontal and vertical target, performed horizontal and vertical active sinusoidal head rotations in light and darkness while looking straight ahead (VOR task) or fixated straight ahead and in four directions of gaze. The eyes of each participant were videotaped and reviewed twice to determine the SBR. Parametric and non-parametric tests were used to analyze the data. Results: The median SBR during fixation straight ahead was seven blinks/minute, which was similar to the SBR during horizontal saccades and horizontal smooth pursuit tasks. The median SBR during vertical smooth pursuit and vertical saccades were significantly lower than during fixation (p≤0.042). The median SBR during the VOR task in light and horizontal VOR in darkness were significantly higher than during fixation (p=0.019-0.024). Conclusions: The median SBR during visual fixation was lower than that reported previously in 5-14 years-old children during rest or 11-20 years-old subjects during quiet conversation. The median SBR was even lower during vertical smooth pursuit and saccades tasks. This may be due to differences in concentration required for visual fixation in general and vertical visual tasks more specifically. The higher SBR during the VOR may be due to drying of the eyes during head shaking.
Linking Exponential Components to Kinetic States in Markov Models for Single-Channel Gating

Discrete state Markov models have proven useful for describing the gating of single ion channels. Such models predict that the dwell-time distributions of open and closed interval durations are described by mixtures of exponential components, with the number of exponential components equal to the number of states in the kinetic gating mechanism. Although the exponential components are readily calculated (Colquhoun and Hawkes, 1982, Phil. Trans. R. Soc. Lond. B. 300:1-59), there is little practical understanding of the relationship between components and states, as every rate constant in the gating mechanism contributes to each exponential component. We now resolve this problem for simple models. As a tutorial we first illustrate how the dwell-time distribution of all closed intervals arises from the sum of constituent distributions, each arising from a specific gating sequence. The contribution of constituent distributions to the exponential components is then determined, giving the relationship between components and states. Finally, the relationship between components and states is quantified by defining and calculating the linkage of components to states. The relationship between components and states is found to be both intuitive and paradoxical, depending on the ratios of the state lifetimes. Nevertheless, both the intuitive and paradoxical observations can be described within a consistent framework. The approach used here allows the exponential components to be interpreted in terms of underlying states for all possible values of the rate constants, something not previously possible.
Vitamin D, Vitamin D Binding Protein, and Longitudinal Outcomes in COPD

Background Associations between Vitamin D3 [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported. We aimed to further investigate these associations on longitudinal outcomes. Methods 426 COPD patients from western Norway, GOLD stage II-IV, aged 40–76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency. Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively. Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression. Results 1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01). Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death. Conclusion Severe vitamin D deficiency may affect decline in lung function parameters in COPD. Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression.
Evolutionary lineages of Actinobacillus actinomycetemcomitans bear diverse traits to support roles as a member of normal flora and as a pathogen

8 REVIEW OF THE LITERATURE 10 1. Periodontitis 10 1.1 General characteristics and classification 10 1.2 Oral biofilms 10 1.3 Actinobacillus actinomycetemcomitans in periodontitis 12 2. Evolutionary lineages of A. actinomycetemcomitans 14 2.1 Population structure 14 2.2 Natural transformation 16 2.3 Intraspecies diversity 17 2.4 Serotypes and serotype-specific antigens 19 2.5 Serotypes vs. genotypes 22 3. Actinobacillus actinomycetemcomitans and systemic host responses 23 3.1 Periodontitis and cardiovascular diseases 24 3.2 Actinobacillus actinomycetemcomitans lipopolysaccharide as a stimulant of host responses related to cardiovascular diseases 27 AIMS OF THE STUDY 30 MATERIALS AND METHODS 31 1. Subjects and bacterial strains 31 2. Eukaryotic cells and cell cultures 32 3. Methods 32 3.1 Serotyping 32 3.2 Genotyping 33 3.3 Isolation of lipopolysaccharide 35 3.4 Natural transformation 35 3.5 Isolation of serotype-specific antigen 36 3.6 Characterization of serotype-specific antigen 36 3.7 Isolation and labeling of low density lipoprotein 37 3.8 Low density lipoprotein uptake by macrophages 37 3.9 Cytokine expression 37 3.10 RNA isolation 37 3.11 Real-time PCR 38 3.12 Statistics 38 RESULTS AND DISCUSSION 39 1. Actinobacillus actinomycetemcomitans serotypes in relation to their proportion in subgingival flora 39 2. Natural transformation among Actinobacillus actinomycetemcomitans serotypes 40 3. Serotype-specific antigen of serotype d 42 3.1 Western blot of Actinobacillus actinomycetemcomitans lipopolysaccharide 42 3.2 Characterization of the affinity-purified antigen 42 4. Effects of Actinobacillus actinomycetemcomitans lipopolysaccharide on murine macrophages 44 4.1 Foam cell formation 44 4.2 Expression of SR-BI and ABCA-1 mRNA 45