Miracle-dz/UniFAR-FTUs huggingface dataset:
Some chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features

ABSTRACT Colorectal cancer (CRC) is the second leading cause of death among cancer patients in the Northern countries. CRC can reappear a long time after treatment. Recent clinical studies demonstrated that, in response to chemotherapy, cancer cells may undergo stress-induced premature senescence (SIPS), which typically results in growth arrest. Nonetheless, these senescent cells were reported to divide in an atypical manner and thus contribute to cancer re-growth. Therefore, we examined if SIPS escape may follow treatment with chemotherapeutics used clinically: 5-fluorouracil (5-FU), oxaliplatin (OXA) and irinotecan (IRINO). To mimic the therapeutic regimes we exposed human colon cancer HCT116 and SW480 cells to repeated cycles of drug treatment. The cells treated with 5-FU or IRINO exhibited several hallmarks of SIPS: growth arrest, increased size and granularity, polyploidization, augmented activity of the SA-β-galactosidase, accumulation of P21 and CYCLIN D1 proteins, and the senescence-associated secretory phenotype. Moreover, re-population of the cancer cell cultures was delayed upon treatment with the senescence-inducing agents. At the same time, we detected a subpopulation of senescent colon cancer cells with features of stemness: elevated NANOG expression, exclusion of Hoechst 33342 (typical for side population) and increased CD24 expression. Additionally, rare, polyploid cells exhibited blastocyst-like morphology and produced progeny. In parallel, majority of chemotherapeutics-treated cells underwent mesenchymal to epithelial transition, as the percentage of CD44-positve cells was reduced, and levels of E-cadherin (epithelial marker) were elevated. Our study demonstrates that a subpopulation of chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features. This may contribute to their resistance to chemotherapy and their ability to re-grow cancer after completion of therapeutic intervention.
Cystic Fibrosis-associated Mutations at Arginine 347 Alter the Pore Architecture of CFTR

Arginine 347 in the sixth transmembrane domain of cystic fibrosis transmembrane conductance regulator (CFTR) is a site of four cystic fibrosis-associated mutations. To better understand the function of Arg-347 and to learn how mutations at this site disrupt channel activity, we mutated Arg-347 to Asp, Cys, Glu, His, Leu, or Lys and examined single-channel function. Every Arg-347 mutation examined, except R347K, had a destabilizing effect on the pore, causing the channel to flutter between two conductance states. Chloride flow through the larger conductance state was similar to that of wild-type CFTR, suggesting that the residue at position 347 does not interact directly with permeating anions. We hypothesized that Arg-347 stabilizes the channel through an electrostatic interaction with an anionic residue in another transmembrane domain. To test this, we mutated anionic residues (Asp-924, Asp-993, and Glu-1104) to Arg in the context of either R347E or R347D mutations. Interestingly, the D924R mutation complemented R347D, yielding a channel that behaved like wild-type CFTR. These data suggest that Arg-347 plays an important structural role in CFTR, at least in part by forming a salt bridge with Asp-924; cystic fibrosis-associated mutations disrupt this interaction.
Genome Wide Gene Expression Profiling and Molecular Classification of Renal Cell Cancer Subtypes

Renal Cell Carcinoma (RCC) is one of the most common malignancy and the sixth cause of leading death from the cancer. In this study, our aim is to identify biomarker candidates expressed at different levels between subtypes of RCC for potential new therapy for RCC. A total of 1,020 raw RNA-Seq counts of renal cancer dataset including 606 KIRP, 323 KIRC and 91 KICH were obtained from the Cancer Genome Atlas (TCGA) Project. Five statistical learning methods including support vector machines (SVM), random forests (RF), penalized discriminant analysis (PDA), naïve bayes (NB) and knearest neighbors (KNN) were applied on the purpose of classification. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis were also conducted for a deeper understanding of differentially expressed genes in three renal cancer subtypes. We identified 181 up-regulated and 69 down-regulated genes that showed a significant differential expression between cancer samples. Classification analysis resulted that integrating these genes in a statistical learning framework perform between 90.7-94.6% accuracy, 81.4-91.2% sensitivity and 92.9-97.0% specificity. Our findings showed a few DEGs including NPK, HRNPLT, ARF1 and TTR might contain a critical role in RCC. Furthermore, study demonstrated using the DEGs as the high rate hit distinguish and classification for RCC subtypes.
Lack of Cross–Reactivity between Casein and Gliadin in Sera from Coeliac Disease Patients

Background: While searching for antigliadin and anticasein antibodies in sera from coeliac patients we investigated more than 20 persons suffering from this enteropathy. In some of sera, we registered antibodies against gliadin and in parallel the appearance of anticasein antibodies. A high percentage of glutamic acid has been proven by amino acid analysis in both these proteins. Therefore we try to demonstrate the existence of cross–reactivity between them in sera from coeliac patients. Methods: We analyzed sera from 5 adult patients by using Western blot (SDS–PAGE and immunoblot assay). All of them had previously proven serum antibodies against casein and gliadin. In the procedure, antigliadin–antibodies were removed from sera by adsorption with gliadin. Adsorbed antibodies were then eluted from the adsorbent. Results: Adsorbed samples retained anticasein activity. Eluates had a strong reactivity to gliadin but not to casein. Conclusion: No cross–reactivity restricted to any of the immunoglobulin isotypes (IgG, IgM, IgA) had been proven between these two proteins. Before the final conclusion, we believe the study has to be completed by using partly of totally disassembled proteins by intestinal enzymes. It might be that enzymatic digestion could open some epitopes shared by both these proteins.
Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3).

BACKGROUND Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. MATERIALS AND METHODS Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. RESULTS A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1-2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. CONCLUSION Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. IMPLICATIONS FOR PRACTICE Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed mechanism of action, palbociclib-related neutropenia differs in its clinical time course, patterns, and consequences from those seen with chemotherapy. Neutropenia can be effectively managed by a dose reduction, interruption, or cycle delay without compromising efficacy. A significant efficacy gain and a favorable safety profile support the consideration of incorporating palbociclib into the routine management of HR-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer.
Growth Hormone Releasing Hormone Expression During Postnatal Development in Growth Hormone-Deficient Ames Dwarf Mice:mRNA in situ Hybridization

Several genetic mutations in mice and rats that produce lifelong growth hormone (GH) deficiency result in overexpression of GH-releasing hormone (GHRH) mRNA in hypothalamic arcuate nucleus neurons. In order to examine the development of this condition, GHRH mRNA expression was quantified in Ames dwarf (df/df) and normal (DF/? ) mice at 1 (day of birth), 3, 7, 14, 21 and 60 postnatal days (d) following in situ hybridization. Total mRNA was assessed using computer-assisted densitometry after X-ray film autoradiography, and mRNA expression per neuron was quantified by counts of grains per cell after emulsion autoradiography. Total GHRH mRNA was the same in dwarf and normal mice at 1, 3 and 7d. GHRH mRNA in dwarfs increased at 14d to 240% of that in DF/? (p < 0.005); the percentage overexpression in dwarf mice remained ≧200% through 60d, although total GHRH mRNA increased in both dwarfs and normals during this period. GHRH mRNA per neuron was the same in normal and dwarf mice at 1d, then increased in dwarfs to 190% of that in normals at 3d (p < 0.05), and rose to 300% of normal levels by 7d and beyond (p < 0.005). There was no sexual dimorphism in expression by either measure in normal or dwarf mice. These results indicate that an increase in GHRH mRNA in Ames dwarf mice is first detectable at 3d, a period of approximately 7d after the failure to initiate GH production, which occurs normally at embryonic day 17.5. The onset of GHRH overexpression occurs earlier than the decline of either hypophysiotropic somatostatin or dopamine in Ames dwarf mice. This difference may be due to the stimulatory action of GHRH, as opposed to the inhibitory effects of factors examined previously.
Inertial Navigation System Alignment Based on Fading Kalman Filter and Fixed Point Smoother

This study concerns the divergence problem of Kalman filter (KF) in the strapdown inertial navigation system (SINS) initial alignment. Fading Kalman filter (FKF) and fixed point smoother (FPS) are investigated in this work, and an improved alignment algorithm is proposed. FKF ensures the fast convergence of filter, and the accuracy loss of FKF is compensated by FPS. A performance comparison between traditional KF alignment algorithm and the proposed algorithm demonstrates that the proposed algorithm performs better in terms of rapidity, convergence and accuracy.
Prediction of ligand binding sites using homologous structures and conservation at CASP8

The critical assessment of protein structure prediction experiment is a blind assessment of the prediction of protein structure and related topics including function prediction. We present our results in the function/binding site prediction category. Our approach to identify binding sites combined the use of the predicted structure of the targets with both residue conservation and the location of ligands bound to homologous structures. We obtained an average coverage of 83% and 56% accuracy. Analysis of our predictions suggests that overprediction reduces the accuracy obtained due to large areas of conservation around the binding site that do not bind the ligand. In some proteins such conserved residues may have a functional role. A server version of our method will soon be available. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

Iron replacement improves clinical status in iron‐deficient patients with heart failure (HF), but the pathophysiology is poorly understood. Iron is essential not only for erythropoiesis, but also for cellular bioenergetics. The impact of myocardial iron deficiency (MID) on mitochondrial function, measured directly in the failing human heart, is unknown.
Minimizing Latency to Support VR Social Interactions Over Wireless Cellular Systems via Bandwidth Allocation

Immersive social interactions of mobile users are soon to be enabled within a virtual space, by means of virtual reality (VR) technologies and wireless cellular systems. In a VR mobile social network, the states of all interacting users should be updated synchronously and with low latency via two-way communications with edge computing servers. The resulting end-to-end latency depends on the relationship between the virtual and physical locations of the wireless VR users and of the edge servers. In this letter, the problem of analyzing and optimizing the end-to-end latency is investigated for a simple network topology, yielding important insights into the interplay between physical and virtual geometries.
Validation of the Pockit Dengue Virus Reagent Set for Rapid Detection of Dengue Virus in Human Serum on a Field-Deployable PCR System

ABSTRACT Dengue virus (DENV) infection, a mosquito-borne disease, is a major public health problem in tropical countries. Point-of-care DENV detection with good sensitivity and specificity enables timely early diagnosis of DENV infection, facilitating effective disease management and control, particularly in regions of low resources. The Pockit dengue virus reagent set (GeneReach Biotech), a reverse transcription insulated isothermal PCR (RT-iiPCR), is available to detect all four serotypes of DENV on the field-deployable Pockit system, which is ready for on-site applications. In this study, analytical and clinical performances of the assay were evaluated. The index assay did not react with 14 non-DENV human viruses, indicating good specificity. Compared to the U.S. CDC DENV-1–4 real-time quantitative RT-PCR (qRT-PCR) assay, testing with serial dilutions of virus-spiked human sera demonstrated that the index assay had detection endpoints that were separately comparable with the 4 serotypes. Excellent reproducibility was observed among repeat tests done by six operators at three sites. In clinical performance, 195 clinical sera collected around Kaohsiung city in 2012 and 21 DENV-4-spiked sera were tested with the RT-iiPCR and qRT-PCR assays in parallel. The 121 (11 DENV-1, 78 DENV-2, 11 DENV-3, and 21 DENV-4) qRT-PCR-positive and 95 qRT-PCR-negative samples were all positive and negative by the RT-iiPCR reagent results, respectively, demonstrating high (100%) interrater agreement (95% confidence interval [CI95%], ∼98.81% to 100%; κ = 1). With analytical and clinical performance equivalent to those of the reference qRT-PCR assay, the index PCR assay on the field-deployable system can serve as a highly sensitive and specific on-site tool for DENV detection.
Transcriptional Signatures of Sleep Duration Discordance in Monozygotic Twins

Introduction Habitual short sleep duration is associated with adverse metabolic, cardiovascular, and inflammatory effects. Co-twin study methodologies account for familial (eg, genetics and shared environmental) confounding, allowing assessment of subtle environmental effects, such as the effect of habitual short sleep duration on gene expression. Therefore, we investigated gene expression in monozygotic twins discordant for actigraphically phenotyped habitual sleep duration. Methods Eleven healthy monozygotic twin pairs (82% female; mean age 42.7 years; SD = 18.1), selected based on subjective sleep duration discordance, were objectively phenotyped for habitual sleep duration with 2 weeks of wrist actigraphy. Peripheral blood leukocyte (PBL) RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. Differential gene expression was determined between paired samples and mapped to functional categories using Gene Ontology. Finally, a more comprehensive gene set enrichment analysis was performed based on the entire PBL transcriptome. Results The mean 24-hour sleep duration of the total sample was 439.2 minutes (SD = 46.8 minutes; range 325.4-521.6 minutes). Mean within-pair sleep duration difference per 24 hours was 64.4 minutes (SD = 21.2; range 45.9-114.6 minutes). The twin cohort displayed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with up-regulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Unexpectedly, genes down-regulated in short sleep twins were highly enriched in immuno-inflammatory pathways such as interleukin signaling and leukocyte activation, as well as developmental programs, coagulation cascade, and cell adhesion. Conclusions Objectively assessed habitual sleep duration in monozygotic twin pairs appears to be associated with distinct patterns of differential gene expression and pathway enrichment. By accounting for familial confounding and measuring real life sleep duration, our study shows the transcriptomic effects of habitual short sleep on dysregulated immune response and provides a potential link between sleep deprivation and adverse metabolic, cardiovascular, and inflammatory outcomes.
Heart rate analysis in a conversation on video chat for development of a chat robot supporting to build a relationship

In recent years, opportunities to communicate has been decreasing by the increasing number of an elderly person who lives alone, social withdrawal of young people and so on. For the solution of this problem, a participation of the robot as a mediator of conversation between people can become a support for making a relationship. In this study, the authors experimented interactive experiment by matching pairs matched by co-occurrence and mutual assistance matching system using personal characteristics like abilities or interest. When people communicate with someone, their physiological phenomenon such as a heartbeat or breath interval occurring synchronously is observed. It is called entrainment. The authors acquired heart beats of a subject in conversation. In addition, the authors analyzed LF/HF ratio by heart rate value. For activation of heart rate synchronization, the interactive experiment was carried out by video chat and subjects could watch partner's face. As a result, the authors found that there are some portion where the transition is synchronized. Moreover, stress tended to decrease as the experiment progressed regardless of topics.
Graphene–Silver Hybrid Metamaterial for Tunable and High Absorption at Mid-Infrared Waveband

We proposed a hybrid metamaterial structure based on graphene-silver, which has tunable and efficient light-absorbing performance at the mid-infrared regime. It is shown that this model can absorb light effectively with a maximum of 100% at the absorption peak wavelength. In addition, the absorption peak wavelength can be adjusted flexibly by changing parameters, including the chemical potential applied to graphene or other structural parameters of the structure. This nearly perfect absorption capability is attributed to the synergetic effects of the localized surface plasmon enhancement of Ag nanoribbon, graphene plasmonics, metal–insulator–graphene mode and Fabry–Perot resonance. This kind of tunable absorber can be used in mid-infrared photodetectors or spectroscopy fields.
The mechanism of manganese dissolution on Li1.6Mn1.6O4 ion sieves with HCl.

Li1.6Mn1. 6O4 is a representative ion sieve material that is used to recover lithium from salt brines and bitterns owing to its high lithium ion adsorption capacity reaching 11.9-44 mg g-1. However, manganese dissolution during acid treatment hinders the industrial application of the material. For investigating the mechanism of manganese dissolution, the precursor Li1.6Mn1. 6O4 and ion sieve H1.6Mn1. 6O4 were prepared and characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), chemical content analyses, diffuse reflectance infrared Fourier-transform spectroscopy (DRIFTS), and X-ray photoelectron spectroscopy (XPS). The results of XRD, SEM, and FT-IR showed that the bulk phase of Li1.6Mn1. 6O4 retained the spinel structure, whereas the lattice diminished during acid treatment. The results of chemical content analyses showed that the bulk phase of Li1.6Mn1. 6O4 contained a few trivalent manganese atoms and that the mean valence of manganese in the material increased during acid treatment. DRIFTS and XPS exhibited that the surface of Li1.6Mn1. 6O4 was mostly full of tetravalent manganese and retained the spinel structure during acid treatment. In the proposed mechanism of manganese dissolution, an electron of trivalent manganese in the bulk phase transfers to the surface and is captured by tetravalent manganese within the acidic environment. Then, tetravalent manganese is converted to bivalent manganese after acquiring sufficient electrons, and dissolution occurs simultaneously.
Effect of Potential Renal Acid Load of Foods on Calcium Metabolism of Renal Calcium Stone Formers

Objectives: Diet has been proposed as a causative factor of hypercalciuria in patients with calcium stones. The aim of this study was to investigate the influence of diet on calcium metabolism of renal stone formers. Methods: Thirty-five renal calcium stone formers were entered in this study. A 2-day recall of dietary intake was obtained from each subject. The food records were coded and computer analyzed for total energy, protein, fat, carbohydrate, sodium, potassium, calcium, magnesium, phosphate, oxalate, vitamin C and fiber. Daily potential renal acid load (PRAL) of the diet was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. A fasting blood sample was drawn and a 24-hour urine collection were obtained for analyses of calcium, phosphate and creatinine. Serum osteocalcin was also analyzed. A fasting 2-hour urine sample was collected in the morning for hydroxyproline, pyridinium cross-links and creatinine. Results: The mean daily dietary PRAL of renal stone formers was 22.4 ± 15.7 (range 4.2–65.8) mEq/day. Regression analysis demonstrated that urinary calcium excretion is dependent on daily protein intake and dietary PRAL, whereas the urinary pyridinium cross-links/creatinine ratio is inversely dependent on daily calcium intake. The urinary pyridinium cross-links/creatinine ratio was significantly lower in patients on a low calcium diet (<600 mg/day) than in other patients (19.5 ± 7.8 vs. 27.3 ± 7.5 nM/mM, p = 0.008). No significant difference was observed between the 2 groups for daily urinary calcium (254 ± 109 vs. 258 ± 140 mg/day), serum osteocalcin (8.2 ± 3.3 vs. 6.2 ± 2.4 ng/ml) and urinary hydroxyproline/creatinine (14.1 ± 7.4 vs. 10.3 ± 4 mg/g). Conclusions: The urinary calcium excretion of renal stone formers seems to be dependent on dietary acid load rather than dietary calcium intake. In patients consuming an acidifying diet a restriction of calcium intake could increase bone resorption leading to a progressive bone loss.