Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives

Microtubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells.
Awareness, prevalence, treatment, and control of type 2 diabetes in a semi-urban area of Nepal: Findings from a cross-sectional study conducted as a part of COBIN-D trial

Background Type 2 diabetes is an escalating public health problem in Nepal. The current study aims to assess the prevalence, associated factors, awareness, treatment, and control of type 2 diabetes in a semi-urban area of Nepal. Methods A population-based cross-sectional survey was conducted including 2,310 adults aged 25 years or above from a semi-urban area of Lekhnath Municipality of Nepal, during October 2016 to April 2017 using the World Health Organization (WHO) STEPS approach. Data on demographics, behavioral risk factors, blood pressure, anthropometric measurements (weight, height, waist and hip circumference), and fasting blood glucose were collected by face-to-face interviews during a door-to-door visit. Participants were considered to have type 2 diabetes if they had previously been diagnosed by a physician and/or were on antidiabetic medications and/or had fasting blood glucose ≥ 7.0 mmol/L. Participants were classified as being aware of their diabetes conditions if they had earlier been told that they had type 2 diabetes. Treatment of diabetes among those aware was if participants received any kind of medication treatment or counseling, and control of diabetes among those treated was defined as fasting blood glucose level was <7.0 mmol/L. Odds Ratio (OR) with 95% Confidence Interval (CI) was used to determine the strength of association. Results The prevalence of type 2 diabetes was 11.7% (95% CI: 10.5–13.1). Among type 2 diabetes participants, 65% were aware of their disease, 94% of those who were aware received treatment, and 21% of the treated subjects had their diabetes under control. Factors significantly associated with type 2 diabetes were older age (OR = 3.2 for age group 45–54 years, OR = 3.8 for age group 55–64 years), Janajati ethnicity (OR = 1.4), abdominal obesity (OR = 2.3), being overweight or obese (OR = 1.4), and hypertension (OR = 2.0), while protective factors included being a female (OR = 0.4), medium physical activity (OR = 0.3), high physical activity (OR = 0.2), and not having family history of diabetes (OR = 0.3). Conclusions The study revealed a high prevalence of type 2 diabetes among adults. Older age, male gender, Janajati ethnicity, abdominal obesity, overweight or obesity, hypertension, low physical activity, and family history of diabetes were associated with type 2 diabetes. Immediate public health and individual measures are warranted to reduce further burden of type 2 diabetes.
Leaf-level photosynthetic capacity dynamics in relation to soil and foliar nutrients along forest–savanna boundaries in Ghana and Brazil

Forest-savanna boundaries extend across large parts of the tropics but the variability of photosynthetic capacity in relation to soil and foliar nutrients across these transition zones is poorly understood. For this reason, we compared photosynthetic capacity (maximum rate of carboxylation of Rubisco at 25 C° (Vcmax25), leaf mass, nitrogen (N), phosphorus (P) and potassium (K) per unit leaf area (LMA, Narea, Parea and Karea, respectively), in relation to respective soil nutrients from 89 species at seven sites along forest-savanna ecotones in Ghana and Brazil. Contrary to our expectations, edaphic conditions were not reflected in foliar nutrient concentrations but LMA was slightly higher in lower fertility soils. Overall, each vegetation type within the ecotones demonstrated idiosyncratic and generally weak relationships between Vcmax25 and Narea, Parea and Karea. Species varied significantly in their Vcmax25 ↔ Narea relationship due to reduced investment of total Narea in photosynthetic machinery with increasing LMA. We suggest that studied species in the forest-savanna ecotones do not maximize Vcmax25 per given total Narea due to adaptation to intermittent water availability. Our findings have implications for global modeling of Vcmax25 and forest-savanna ecotone productivity.
Sequential Versus Combination Therapy of Metastatic Colorectal Cancer Using Fluoropyrimidines, Irinotecan, and Bevacizumab: A Randomized, Controlled Study-XELAVIRI (AIO KRK0110).

PURPOSE The XELAVIRI trial investigated the optimal treatment strategy for patients with untreated metastatic colorectal cancer. We tested the noninferiority of initial treatment with a fluoropyrimidine plus bevacizumab, followed by the addition of irinotecan at first progression (arm A) versus upfront use of fluoropyrimidine plus irinotecan plus bevacizumab (arm B) in a 1:1 randomized, controlled phase III trial. METHODS The primary efficacy end point was time to failure of the strategy (TFS). Given a 90% CI, a power of 70%, and a one-sided α of . 05, the margin for noninferiority was set at 0.8. In the case of demonstrated noninferiority of TFS, an analysis of symptomatic toxicities during TFS would define the superior strategy. Secondary end points included the effect of molecular subgroups on efficacy parameters. RESULTS A total of 421 randomly assigned patients (arm A: n = 212; arm B: n = 209) formed the full analysis set. Median age was 71 and 69 years, respectively. Noninferiority of TFS was not shown (hazard ratio [HR], 0.86; 90% CI, 0.73 to 1.02). In detail, patients with RAS/BRAF wild-type tumors benefitted from combination chemotherapy (HR, 0.61; 90% CI, 0.46 to 0.82; P = .005), whereas patients with RAS mutant tumors (HR, 1.09; 90% CI, 0.81 to 1.46; P = .58) did not (Cox model for interaction of study arm and RAS status: P = .03). Comparable results were obtained for overall survival. CONCLUSION Noninferiority of sequential escalation therapy compared with initial combination chemotherapy could not be demonstrated for TFS. RAS status may be important to guide therapy as treatment of patients with upfront combination therapy was clearly superior in RAS/BRAF wild-type tumors, whereas sequential escalation chemotherapy seems to provide comparable results in patients with RAS mutant tumors.
Generalization and search in risky environments

How do people pursue rewards in risky environments, where some outcomes should be avoided at all costs? We investigate participants’ search for spatially correlated rewards in scenarios where one must avoid sampling rewards below a given threshold. This requires participants to not only balance exploration and exploitation, but also to reason about how to avoid potentially risky areas of the search space. Within risky versions of the spatially correlated multi-armed bandit task, we show that participants’ behavior is aligned well with a Gaussian process function learning algorithm, which chooses points based on a safe optimization routine. Moreover, using leave-one-block-out cross-validation, we find that participants adapt their sampling behavior to the riskiness of the task, although the underlying function learning mechanism remains relatively unchanged. These results show that participants can adapt their search behavior to the adversity of the environment and enrich our understanding of adaptive behavior in the face of risk and uncertainty.
Cell‐Compatible Nanoprobes for Imaging Intracellular Phosphatase Activities

Phosphatases play an important role in cell biology, but only a few probes are suitable for selectively imaging phosphatase activity in live cells, because the current probes require cell fixation or exhibit considerable cytotoxicity. Herein, we show that conjugating a d‐peptide to a quinazolinone derivative generates cell‐compatible, biostable probes for imaging the phosphatase activity inside live cells. Moreover, our results show that inhibiting ectophosphatases is a critical factor for imaging intracellular phosphatases. As the first example of using selective inhibitors to ensure intracellular function of molecular probes, this work illustrates a facile approach to design molecular probes for profiling the activities of enzymes in a spatial, selective manner in a complicated environment.
Characterization of the In Vitro Inhibitory Potential of the Oligonucleotide Imetelstat on Human Cytochrome P450 Enzymes with Predictions of In Vivo Drug-Drug Interactions

Imetelstat, a 13-base oligonucleotide (5′-TAGGGTTAGACAA-3′), is a potent, investigational telomerase inhibitor in clinical development for the treatment of hematologic myeloid malignancies. Modifications to imetelstat oligonucleotide chemistry include an N3′–P5′ thio-phosphoramidate backbone linkage to improve biologic stability and the addition of a palmitoyl tail at the 5′-position to enhance cellular membrane permeability. Other oligonucleotides have been previously shown to have in vitro test-system–dependent outcomes when potent cytochrome P450 inhibition in human liver microsomes (HLM) is observed, but such inhibition is not observed in cryopreserved human hepatocytes (CHH). Outcomes in CHH are consistent with clinical reports in which no interactions were reported. In the present study, imetelstat was evaluated for in vitro inhibition of eight P450 enzymes, namely CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in CHH (0.5 million cells/ml). Assays were performed using validated conditions, including short substrate times (10 minutes), and at the approximate substrate Km concentration. Imetelstat was found to have little to no inhibition of all P450 isoforms evaluated, with inhibitor concentration that causes 50% inhibition (IC50) values >100 μM. Maximum percent inhibition values for each P450 isoform at 100 μM imetelstat were <20% except for CYP2C8 activity, which was inhibited by 49%. Using a static mechanistic model, the predicted change in area under the curve of a victim drug coadministered with imetelstat was 1.04-fold, projecting no relevant clinical interaction. Overall, the results from this in vitro study suggest that clinical use of imetelstat is unlikely to affect the pharmacokinetics of concomitant therapies that undergo cytochrome P450-mediated metabolism.
Association between Physical Condition and Body Composition, Nutrient Intake, Sociodemographic Characteristics, and Lifestyle Habits in Older Spanish Adults

In this study, we assessed physical condition and its association with body composition, nutrient intake, sociodemographic characteristics, and lifestyle habits in older Spanish adults. In this cross-sectional study, we investigated 380 individuals (54% women; men aged 55–80 years and women aged 60–80 years) with no previously documented cardiovascular disease. A general questionnaire was used, and body weight, height, fat, appendicular skeletal muscle mass, and waist circumference were assessed. Physical condition measurements included handgrip strength (HGS) and agility/dynamic balance by eight-foot time up-and-go (8-f TUG) test. The lowest maximum HGS score (kg) was found in older participants, inactive men, and men with abdominal obesity. The highest maximum 8-f TUG score (s) was found in older and inactive, low education, low income, and abdominal obesity and overfat participants; 24.5% of participants had low maximum HGS and 36.8% had a high 8-f TUG score. Sex- and/or age-adjusted odds ratio (OR) for low maximum HGS in women, older participants, overweight and overfat participants were 4.6, 2.9, 0.6 and 0.6 respectively. Sex and/or age adjusted OR for high maximum 8-f TUG in women, overweight, overfat, and abdominally obese participants were 2.4, 1.6, 1.7, and 3.4, respectively; in participants with higher education, those who earned €900 or more per month, and slightly active and active participants had OR values of 0.4, 0.4, and 0.3, respectively. Sarcopenia incidence was 0.3%; however, 4.5% of men and 19.1% of women registered low physical condition (high and low scores in 8-f TUG and HGS tests, respectively). Overall, 36.8%, 24.5%, and 0.3% of participants had high maximum 8-f TUG score, low maximum HGS, and sarcopenia, respectively. Prevalence of these low values varies according to sociodemographic and body composition variables.
3D Imaging Based on Depth Measurement Technologies

Three-dimensional (3D) imaging has attracted more and more interest because of its widespread applications, especially in information and life science. These techniques can be broadly divided into two types: ray-based and wavefront-based 3D imaging. Issues such as imaging quality and system complexity of these techniques limit the applications significantly, and therefore many investigations have focused on 3D imaging from depth measurements. This paper presents an overview of 3D imaging from depth measurements, and provides a summary of the connection between the ray-based and wavefront-based 3D imaging techniques.
Temporal and Spatial Differentiations in Environmental Governance

With the general degradation of environmental carrying capacity in recent years, many developing countries are facing with the dual task of economic development and environmental protection. To explore the issue of urban environmental governance, in this research, we establish a Data Envelopment Analysis (DEA) model to investigate the environmental governance regarding temporal and spatial efficiency. Further, we deconstruct environmental governance efficiency into comprehensive efficiency, pure technical efficiency, and scale efficiency and develop a Tobit model to analyze the influencing factors affecting urban environmental governance efficiency. In addition, the above DEA, Tobit model, and deconstruction of efficiency have been applied to study environmental governance efficiency for the Yangtze River urban agglomeration. Findings include: (1) The gap in environmental governance efficiency between cities is highly noticeable, as the highest efficiency index is 0.934, the lowest is only 0.246, and the comprehensive efficiency index has fallen sharply from 0.708 to 0.493 in the past 10 years; (2) Environmental governance efficiency is basically driven by technological progress, while the scale efficiency change index is the main driver of the technological progress change index; (3) For environmental governance efficiency, urbanization and capital openness are irrelevant factors, economic level and urban construction are unfavorable factors, and industrial structure and population density are favorable factors. These findings will help urban agglomerations to effectively avoid the adverse effects of environmental governance efficiency in economic development, and achieve a coordinated development of urban construction and environmental governance.
Heteroepitaxial Growth of T-Nb2O5 on SrTiO3

There is a growing interest in exploiting the functional properties of niobium oxides in general and of the T-Nb2O5 polymorph in particular. Fundamental investigations of the properties of niobium oxides are, however, hindered by the availability of materials with sufficient structural perfection. It is expected that high-quality T-Nb2O5 can be made using heteroepitaxial growth. Here, we investigated the epitaxial growth of T-Nb2O5 on a prototype perovskite oxide, SrTiO3. Even though there exists a reasonable lattice mismatch in one crystallographic direction, these materials have a significant difference in crystal structure: SrTiO3 is cubic, whereas T-Nb2O5 is orthorhombic. It is found that this difference in symmetry results in the formation of domains that have the T-Nb2O5 c-axis aligned with the SrTiO3 <001>s in-plane directions. Hence, the number of domain orientations is four and two for the growth on (100)s- and (110)s-oriented substrates, respectively. Interestingly, the out-of-plane growth direction remains the same for both substrate orientations, suggesting a weak interfacial coupling between the two materials. Despite challenges associated with the heteroepitaxial growth of T-Nb2O5, the T-Nb2O5 films presented in this paper are a significant improvement in terms of structural quality compared to their polycrystalline counterparts.
Modelo analítico para el estudio de la torsión en rotores flexibles

RESUMEN Este trabajo de investigacion presenta un planteamiento matematico para el analisis dinamico de rotores flexibles. Parte de las expresiones de la energia cinetica, potencial y funcion de disipacion de Rayleigh generadas para un disco mediante el Metodo de los Elementos Finitos. Luego, integrando a lo largo de la longitud del elemento, se obtienen las expresiones para un elemento de rotor. Aplicando las ecuaciones de Lagrange se deducen las ecuaciones de movimiento del sistema. La modelizacion matematica se realiza para las componentes principales: los apoyos, elementos no necesariamente rigidos que se denominan "estaticos" aun cuando estan sujetos a vibraciones, y la parte rotativa. Las dos partes requieren de tecnicas distintas de simulacion dinamica, lo cual hace necesario aplicar, en este caso, las conocidas "Tecnicas de Sintesis de Componentes" para aprovechar los resultados obtenidos de la simulacion independiente de cada parte. La interaccion entre la parte "estatica" y la parte rotativa, a traves de los apoyos, genera unos esfuerzos de accion reaccion, mediante los cuales es posible acoplar los sistemas de ecuaciones de las dos partes.El modelo matematico desarrollado, calcula los parametros modales y la respuesta en el estado estacionario y transitorio, teniendo en cuenta, o no, el propio peso, la no linealidad en los apoyos y principalmente la flexibilidad a torsion del rotor. El sistema de ecuaciones se linealiza a traves del metodo iterativo de Newton Raphson y las ecuaciones se integran utilizando el metodo de Newmark. PALABRAS CLAVE: Dinamica de rotores flexibles, sintesis de componentes, no-linealidad, flexibilidad a torsion. ABSTRACT This job shows a mathematical formulation in order to study the torsional behavior in a fexible rotor. The model starts calculating kinetic energy, potential energy and the Rayleigh dissipation function. From both, energy expressions and by means of the Finite Element Method, get the fnite element of a single disk. Integrating it, we can get the expression to the rotor element. Using the Lagrange Equations is possible deduce the equations system of movement in order to study the rotors dynamic including torsional behavior.The mathematical model has into account the main components of the system: First, the support structure whit its bearings, and secondly the rotative part. Both of them are modeled using different analytical technics, so it uses the component synthesis in order to introduce the behavior of the support structure where the rotor is grounded. The developed mathematical model calculates both, the model parameters stationary response and resolves the transitory state. KEYWORDS: Flexible rotors, dynamic of rotor, component synthesis, torsional fexibility.
Endowment Effect: Trading for Oneself Versus Trading for Others

Prior research on the endowment effect has tended to focus on decisions made by individuals acting on their own account rather than on others’ behalf. This article reports on three experiments that modeled this “for-self” versus “for-others” distinction and measured its effects on prices. Specifically, our participants who were asked to make trading decisions for other people subsequently reported decreases in the endowment effect. We concluded that, in the context of the trading of goods, perceived ownership and differences in focus on the traded products’ positive and negative features mediated the diminished endowment effect our experiments identified.
Real‐time scatter estimation for medical CT using the deep scatter estimation: Method and robustness analysis with respect to different anatomies, dose levels, tube voltages, and data truncation

PURPOSE X-ray scattering leads to CT images with a reduced contrast, inaccurate CT values as well as streak and cupping artifacts. Therefore, scatter correction is crucial to maintain the diagnostic value of CT and CBCT examinations. However, existing approaches are not able to combine both high accuracy and high computational performance. Therefore, we propose the deep scatter estimation (DSE): a deep convolutional neural network to derive highly accurate scatter estimates in real time. METHODS Gold standard scatter estimation approaches rely on dedicated Monte Carlo (MC) photon transport codes. However, being computationally expensive, MC methods cannot be used routinely. To enable real-time scatter correction with similar accuracy, DSE uses a deep convolutional neural network that is trained to predict MC scatter estimates based on the acquired projection data. Here, the potential of DSE is demonstrated using simulations of CBCT head, thorax, and abdomen scans as well as measurements at an experimental table-top CBCT. Two conventional computationally efficient scatter estimation approaches were implemented as reference: a kernel-based scatter estimation (KSE) and the hybrid scatter estimation (HSE). RESULTS The simulation study demonstrates that DSE generalizes well to varying tube voltages, varying noise levels as well as varying anatomical regions as long as they are appropriately represented within the training data. In any case the deviation of the scatter estimates from the ground truth MC scatter distribution is less than 1.8% while it is between 6.2% and 293.3% for HSE and between 11.2% and 20.5% for KSE. To evaluate the performance for real data, measurements of an anthropomorphic head phantom were performed. Errors were quantified by a comparison to a slit scan reconstruction. Here, the deviation is 278 HU (no correction), 123 HU (KSE), 65 HU (HSE), and 6 HU (DSE), respectively. CONCLUSIONS The DSE clearly outperforms conventional scatter estimation approaches in terms of accuracy. DSE is nearly as accurate as Monte Carlo simulations but is superior in terms of speed (≈10 ms/projection) by orders of magnitude.
The Limits of Emotion in Moral Judgment

This chapter argues that our best science supports the rationalist idea that, independent of reasoning, emotions are not integral to moral judgment. There is ample evidence that ordinary moral cognition often involves conscious and unconscious reasoning about an action’s outcomes and the agent’s role in bringing them about. Emotions can aid in moral reasoning by, for example, drawing one’s attention to such information. However, there is no compelling evidence for the decidedly sentimentalist claim that mere feelings are causally necessary or sufficient for making a moral judgment or for treating norms as distinctively moral. The chapter concludes that, even if moral cognition is largely driven by automatic intuitions, these should not be mistaken for emotions or their non-cognitive components. Non-cognitive elements in our psychology may be required for normal moral development and motivation but not necessarily for mature moral judgment.