Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a Bio-Assay for Estrogens using Estrogen Receptor Alpha Gene Expression by MCF7 Cells as Biomarker

Abstract Estrogenic endocrine disruptors (EDCs) have been identified in soil, food, air, and water, and may produce adverse health effects in both humans and wildlife. Various in vitro assays, including the E-screen that measures estrogen dependent proliferation of the MCF-7 human breast cancer cell line, have been developed and implemented to screen for environmental estrogenic EDCs. This study describes a new amendment to the well known E-screen. A direct ELISA to quantify ERα protein levels on MCF-7 cells cultured in a high through put 96-well format were validated as a biomarker for estrogenicity. The ELISA shows that there is an inverse correlation between ERα levels and 17β-estradiol (E2) concentration (R2 = 1). The detection range of the assay is between 1 and 1000 nM for E2. Results obtained with the ERα ELISA showed a good inverse correlation with total cellular LDH levels that is conventionally used to quantify MCF-7 cell proliferation. This ELISA was employed to assess environmental water extracts for estrogenicity.
Algebraic Method for the Analysis of Signaling Crosstalk

A unified mathematical description that expresses the characteristics of whole systems is necessary for an understanding of signal transduction cascades. In this study we explore an algebraic method, named extreme signaling flow, enhanced from the concept of extreme pathway, to analyze signal transduction systems. This method enables us to represent the long-term potentiation (LTP) and the long-term depression (LTD) of hippocampal neuronal plasticity in an integrated simulation model. The model is validated by comparing the results of redundancy, reaction participation, and in silico knockout analysis with biological knowledge available from the literature. The following properties are assumed in these computational analyses: (1) LTP is fault-tolerant under network modification, (2) protein kinase C and MAPK have numerous routes to LTP induction, (3) calcium-calmodulin kinase II has a few routes to LTP induction, and (4) calcineurin has many routes to LTD induction. These results demonstrate that our approach produces an integrated framework for analyzing properties of large-scale systems with complicated signal transduction.
A rare fraction of drug‐resistant follicular lymphoma cancer stem cells interacts with follicular dendritic cells to maintain tumourigenic potential

Follicular lymphoma (FL) comprises nearly 25% of non‐Hodgkin lymphoma cases and is clinically characterized by initial sensitivity to chemotherapy followed by relapse. FL stroma contains a special type of stromal cell found in the germinal centre of lymph nodes—the follicular dendritic cell (FDC). We first isolated tumourigenic cells from the FL cell line FLK‐1 by side population (SP) technique, and found that SP cells, which express ABCG2, were enriched by chemotherapy and radiation treatments. In vitro, SP cells were attracted by and adhered to FDCs through chemokine (C‐X‐C motif) ligand 12/chemokine (C‐X‐C motif) receptor 4 (CXCL12/CXCR4) signalling. In vivo, limiting dilution assays showed SP cells were highly enriched in cancer stem cells (CSC), but required FDC for tumour formation in non‐obese diabetic/severe combined immunodeficiency mice. Treatment with AMD3100, a specific CXCL12/CXCR4 inhibitor, eliminated tumour growth. These findings were then verified with FL cells isolated from an FL patient's ascitic fluid (FLA‐1). Finally, we detected the ABCG2 expressing lymphoma cells in FL clinical specimens. Thus, we found that the highly tumourigenic FL cells having CSC‐like activities (FL‐SC) interact with FDCs in a CXCL12/CXCR4 dependent manner to resist chemotherapy. Our results indicate the importance of FL‐SC and niche cell signalling in maintaining tumourigenicity. These signals represent novel targets for CSC eradication.
Can particle beam therapy be improved using helium ions? – a planning study focusing on pediatric patients

Abstract Aim To explore the potential of scanned helium ion beam therapy (4He) compared to proton therapy in a comparative planning study focusing on pediatric patients. This was motivated by the superior biological and physical characteristics of 4He. Material and methods For eleven neuroblastoma (NB), nine Hodgkin lymphoma (HL), five Wilms tumor (WT), five ependymoma (EP) and four Ewing sarcoma (EW) patients, treatment plans were created for protons and 4He. Dose prescription to the planning target volume (PTV) was 21 Gy [relative biological effectiveness (RBE)] (NB), 19.8 Gy (RBE) (HL), 25.2 Gy (RBE) for the WT boost volume and 54 Gy (RBE) for EP and EW patients. A pencil beam algorithm for protons (constant RBE = 1.1) and 4He was implemented in the treatment planning system Hyperion. For 4He the relative biological effectiveness (RBE) was calculated with a ‘zonal’ model based on different linear energy transfer regions. Results Target constraints were fulfilled for all indications. For NB patients differences for kidneys and liver were observed for all dose-volume areas, except the high-dose volume. The body volume receiving up to 12.6 Gy (RBE) was reduced by up to 10% with 4He. For WT patients the mean and high-dose volume for the liver was improved when using 4He. For EP normal tissue dose was reduced using 4He with 12.7% of the voxels receiving higher doses using protons. For HL and EW sarcoma patients the combination of large PTV volumes with the position of the organs at risk (OARs) obliterated the differences between the two particle species, while patients with the heart close to the PTV could benefit from 4He. Conclusion Treatment plan quality improved with 4He compared to proton plans, but advantages in OAR sparing were depending on indication and tumor geometries. These first results of scanned 4He therapy motivate comprehensive research on 4He, including acquisition of experimental data to improve modeling of 4He.
Comprehensive switching behavior characterization of high speed Gallium Nitride E-HEMT with ultra-low loop inductance

Gallium Nitride has shown its potential over traditional Silicon devices with low switching and conduction losses. However, fast switching transition poses great challenges in dynamic device characterization due to sensitivity to parasitics and high requirement in testing equipment. An accurate switching behavior characterization method is proposed in this paper with loop inductance minimization and flat current shunt resistors. Switching losses for GaN transistor under three different current freewheeling patterns are explored and compared: through upper diode, through upper GaN transistor synchronous operation and through upper GaN reverse conduction, which include all the possible operation conditions in practical industry applications. The overall inductance in main power loop is well designed as low as 1.52nH. It is the first cleanest and most accurate GaN switching waveform ever reported. It is also the first time that GaN switching behavior with current reverse conduction through channel is investigated. The fastest switching speeds are dv/dton = 9.1V/ns, dv/dtoff = 8.6V/ns, and di/dton=7.0A/ns, di/dtoff = 5V/ns. The measured turn-on energy loss is 1. 4μJ at 30V, 20A and 1. 59μJ at 30V, 30A respectively.
Role of Docosahexaenoic Acid in Neuronal Plasma Membranes

The omega-3 fatty acid docosahexaenoic acid (DHA n-3) has long been known to be a major component of phosphoglycerides in the gray matter of mammalian brains. Furthermore, early studies of synaptosomes that had been isolated from gray matter showed that the plasma membranes of the synaptosomes contained DHA n-3 that was selectively esterified to phosphatidylethanolamine, plasmenylethanolamine (alkenylacyl-glycero-phosphorylethanolamine), and phosphatidylserine. In contrast, the phosphatidylcholine in these membranes contained esterified oleic acid, and the sphingomyelin and glycolipids in the membranes contained amide-linked stearic acid instead of a mixture of this acid with other, amide-linked fatty acids. The full implications of this unusual distribution of lipid head groups, esterified fatty acids, and amide-linked fatty acids are unclear, but the phosphoglycerides and sphingosine-containing lipids appear to be distributed asymmetrically between the two leaflets of the plasma membrane lipid bilayer and are likely to contribute to a dynamic lipid substructure. Because very few neuronal plasma membranes have been isolated and characterized to date, a major challenge for the future will be to investigate the composition of the lipid bilayers of different neuronal plasma membranes and identify effects of DHA n-3–containing phosphoglycerides on the ability of the plasma membranes to perform their many different functions. The aim of this Perspective is to stimulate further work in this important area by discussing recent evidence related to the role of neuronal plasma membrane phosphoglycerides in cell signaling.
Phosphorylation and Maximal Activity of Saccharomyces cerevisiae Meiosis-Specific Transcription Factor Ndt80 Is Dependent on Ime2

ABSTRACT The Saccharomyces cerevisiae meiosis-specific transcription factor Ndt80 is responsible for the induction of a class of genes referred to as middle sporulation genes. Among the members of this family are the B-type cyclins and other genes whose products are required for meiotic chromosome division and spore morphogenesis. Inactivation of NDT80 leads to a failure to induce the middle sporulation genes and a subsequent arrest in pachytene. The expression of NDT80 is itself highly regulated. The initial transcription of NDT80 is dependent upon the protein kinase Ime2; once Ndt80 protein accumulates, it activates its own promoter, thus generating an autoactivation loop. In addition to being transcriptionally regulated, Ndt80 protein is posttranslationally regulated. Phosphorylation of Ndt80 occurs coincident with its activation as a transcription factor. If expressed prematurely in meiosis, Ndt80 accumulates initially in an unmodified form that is subsequently modified by phosphorylation. In contrast, Ndt80 expressed in ime2 mutant strains does not become modified and has a reduced ability to activate transcription of its target genes. Ime2 can also phosphorylate Ndt80 in vitro, further supporting a direct role for Ime2 in the phosphorylation of Ndt80. These data indicate that Ime2 plays a novel and previously unexpected role in promoting chromosome dissemination and progress through meiotic development by activating Ndt80.
Estimating Personality from Social Media Posts

An individual's personality determines the probable repertoire of their reactions to a particular situation. A social robot is much more effective if it is able to learn and so take into account the properties of the humans around it, including personalities. We investigate how well personality can be estimated based on modest amounts of speech or writing, which a social robot might (over)hear. Such a technique also permits humans to be able to infer the personalities of other humans 'at a distance' based on their writing in political, hiring, negotiation, and other relationship settings. We design and implement a technique for predicting personality from small amounts of text, with accuracies comparable to inter-human agreement and substantially better than previous algorithmic approaches (except for a few that use much richer data). The technique works for both of the popular personality typologies, the Big Five and the Myers-Briggs. Because the approach does not require a lexicon, it is language independent. We illustrate using eight different languages, including Arabic.
Estimation of conditions evoking fracture in finger bones under pinch loading based on finite element analysis

Abstract A finger finite element (FE) model was created from CT images of a Japanese male in order to obtain a shape-biofidelic model. Material properties and articulation characteristics of the model were taken from the literature. To predict bone fracture and realistically represent the fracture pattern under various loading conditions, the ESI-Wilkins-Kamoulakos rupture model in PAM-CRASH (ESI Group S.A., Paris, France) was utilized in this study with parameter values of the rupture model determined by compression testing and simulation of porcine fibula. A finger pinch simulation was then conducted to validate the finger FE model. The force-displacement curve and fracture load from the pinch simulation was compared to the result of finger pinch test using cadavers. Simulation results are coincident with the test result, indicating that the finger FE model can be used in an analysis of finger bone fracture during pinch accident. With this model, several pinch simulations were conducted with different pinching object’s stiffness and pinching energy. Conditions for evoking finger bone fracture under pinch loading were then estimated based on these results. This study offers a novel method to predict possible hazards of manufactured goods during the design process, thus finger injury due to pinch loading can be avoided.
SLIP1, a Factor Required for Activation of Histone mRNA Translation by the Stem-Loop Binding Protein

ABSTRACT Replication-dependent histone mRNAs are the only eukaryotic cellular mRNAs that are not polyadenylated, ending instead in a conserved stem-loop. The 3′ end of histone mRNA is required for histone mRNA translation, as is the stem-loop binding protein (SLBP), which binds the 3′ end of histone mRNA. We have identified five conserved residues in a 15-amino-acid region in the amino-terminal portion of SLBP, each of which is required for translation. Using a yeast two-hybrid screen, we identified a novel protein, SLBP-interacting protein 1 (SLIP1), that specifically interacts with this region. Mutations in any of the residues required for translation reduces SLIP1 binding to SLBP. The expression of SLIP1 in Xenopus oocytes together with human SLBP stimulates translation of a reporter mRNA ending in the stem-loop but not a reporter with a poly(A) tail. The expression of SLIP1 in HeLa cells also stimulates the expression of a green fluorescent protein reporter mRNA ending in a stem-loop. RNA interference-mediated downregulation of endogenous SLIP1 reduces the rate of translation of endogenous histone mRNA and also reduces cell viability. SLIP1 may function by bridging the 3′ end of the histone mRNA with the 5′ end of the mRNA, similar to the mechanism of translation of polyadenylated mRNAs.
The association of serum vitamin D level with presence of metabolic syndrome and hypertension in middle-aged Korean subjects.

OBJECTIVE To examine the association of serum vitamin D level with metabolic syndrome (MetS) and hypertension (HTN) in middle-aged Korean subjects. DESIGN AND SUBJECTS We conducted a population-based, cross-sectional survey of 1330 participants aged over 40 years (median age 65.8 years) in Chungju, Korea, in 2007. The 324 subjects, who were normotensive in 2003 and who attended a follow-up visit 4 years later, were included in an analysis of the association of serum vitamin D level with the risk of HTN. MEASUREMENTS Serum 25-hydroxy-vitamin D [25(OH)D] and PTH were measured in a central laboratory, using chemiluminescence assays. RESULTS The overall prevalence of the MetS in participants of this study was 45.3%. After adjusting for various covariates, subjects in the highest quintile group (61.4-116.8 nmol/l) compared with the lowest quintile group (10.0-29.7 nmol/l) of 25(OH)D had an odds ratio (OR) for having MetS of 0.35 (95% confidence intervals, CI, 0.22-0.56; P for trend <0.001). The median level of 25(OH)D was 46.8 nmol/l among 324 subjects who were normotensive in 2003. After multiple adjustment, the OR was substantially higher for new HTN (OR 2.74; 95% CI 1.40-5.34) in subjects with serum 25(OH)D levels below the median value compared with those above median. The inverse associations of vitamin D and MetS/HTN were unchanged after adjustment for PTH and serum calcium levels. There was no association between PTH and MetS. CONCLUSIONS We found a strong inverse association of 25(OH)D levels with MetS and HTN in this middle-aged Korean population. Having vitamin D deficiency was associated with an increased risk of having MetS and HTN in this demographic group.
Food–plant niche selection rather than the presence of ant nests explains oviposition patterns in the myrmecophilous butterfly genus Maculinea

It has been suggested that the socially parasitic butterfly Maculinea alcon detects ant odours before ovipositing on initial larval food plants near colonies of its obligate ant host Myrmica ruginodis. It has also been suggested that overcrowding on food plants near M. ruginodis is avoided by an ability to detect high egg loads, resulting in a switch to selecting plants near less suitable ant species. If confirmed, this hypothesis (H1) would have serious implications for the application of current population models aimed at the conservation of endangered Maculinea species, which are based on the null hypothesis (H0) that females randomly select food plants whose flower buds are at a precise phenological stage, making oviposition independent of ants. If H1 were wrong, practical management based upon its assumptions could lead to the extinction of protected populations. We present data for the five European species of Maculinea which show that (i) each oviposits on a phenologically restricted flower–bud stage, which accounts for the apparent host–ant–mediated niche separation in sympatric populations of Maculinea nausithous and Maculinea teleius, (ii) there is no temporal shift in oviposition by Maculinea arion in relation to host ant distribution or egg density, and (iii) oviposition patterns in 13 populations of M.alcon's closest relative, Maculinea rebeli, conform to H0 not H1 predictions. It is concluded that conservation measures should continue to be based on H0.
Characterization of isolated duodenal epithelial cells along a cryptvillus axis in rats fed diets with different iron content

The intestinal mucosa is characterized by cell proliferation, commitment, differentiation, digestion and absorption. These processes occur at specified locations along the crypt to villus axis. A technique is reported for the isolation of cells along this axis which allows the study of any one of these processes in an enriched population of cells. As an example, the uptake of transferrin‐bound iron by enterocytes was studied. Rats were fed diets normal, high (3% carbonyl iron) or low in iron for 12 days. Cells from either the duodenum or ileum were isolated by incubating in a Ca2+‐, Mg2+‐free, cation chelating solution for varying periods. The incorporation of thymidine into DNA was measured in these cells as a marker of the crypt region, while alkaline phosphatase and sucrase activities marked mature enterocytes. The in vivo uptake of transferrin‐bound 59Fe was measured in cells isolated either 2 or 4 h after intravenous injection. This procedure resulted in the isolation of 10 fractions of viable cells. Earlier fractions were enriched at least 10‐fold in villus cells and the last fractions in crypt cells. Cells in intermediate fractions were at various stages of development. Uptake of transferrin‐bound iron into enterocytes was highest with feeding an iron‐loaded diet compared with control or iron‐deficient diets. However, with all diets uptake was highest in crypt cells and this fell at the crypt‐villus junction to be only 25%, as high at the villus tip as the crypt. A technique for the reproducible isolation of viable enterocytes along a crypt‐villus axis is described. Transferrin receptor activity changes with maturation of the enterocyte.
Multiplicity considerations for subgroup analysis subject to consistency constraint

A significant heterogeneity in response across subgroups of a clinical trial implies that the average response from the overall population might not characterize the treatment effect; and as noted by different regulatory guidances, can cause concerns in interpreting study findings and might lead to restricting treatment labeling. However, along with the challenges raised by the heterogeneity, recently there has been growing interest in taking advantage of the expected variability in response across subgroups to increase the chance of success of a trial by designing the trial with objectives of establishing efficacy claims for the total population and a targeted subgroup. For such trials, there have been several approaches to address the multiplicity issue with the two paths of success. This manuscript advocates the utility of setting a threshold on the treatment effect for the subgroups at the design stage to guide determination of the population labeling when significant findings for the total population have been established. Specifically, it proposes that licensing treatment for the total population requires, in addition to significant findings for this population, that the treatment effect in the least benefited (complementary) subgroup meets the treatment effect threshold at a minimum; otherwise, the treatment would be restricted to the targeted subgroup only. Setting such a threshold can be based on clinical considerations, including toxicity and adverse events, in addition to treatment effect in the subgroup. This manuscript expands some of the multiplicity approaches to account for the threshold requirement and investigates the impact of the threshold requirement on study power.
Utility of Motor Evoked Potentials for Intraoperative Nerve Root Monitoring

Summary There is no entirely satisfactory way to monitor nerve root integrity during spinal surgery. In particular, standard free-running electromyography carries a high false-positive rate and some false-negative rate of injury. Stimulated electromyography to direct root stimulation can only be done intermittently, and roots are often inaccessible. This article reviews to what extent muscle motor evoked potential (MEP) monitoring might help. It presents background considerations, describes MEP methodology, and summarizes relevant experimental animal and clinical studies. Based on current evidence, root compromise can cause myotomal MEP deterioration that in some cases may be reversible. However, because of radicular overlap, limited sampling, confounding factors, and response variability, the effects range from no appreciable change to variable degrees of amplitude reduction to disappearance and some false-positive and false-negative results should be expected. For root monitoring, multichannel MEP recordings should span adjacent myotomes and avoid mixed myotome derivations. Only amplitude reduction warning criteria have been studied, but no percentage cutoff consensus has emerged, and this approach is troubled by response variability. There is some evidence that MEPs might reduce false electromyographic results. In conclusion, muscle MEPs could compliment electromyography but seem unlikely to completely solve the problem of nerve root monitoring.