Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells

EGFR tyrosine kinase inhibitors have shown promising efficacy in the treatment of tumors with EGFR mutations and amplifications. However, tyrosine kinase inhibitors have also proven ineffective against most tumors with EGFR wild-type (WT) alleles. Although some genetic changes, including the KRAS mutation, have been shown to confer resistance to tyrosine kinase inhibitors, novel strategies for the treatment of cancer patients with tumors harboring EGFR WT alleles have yet to be thoroughly delineated. The principal objective of this study was to improve our current understanding of drug interactions between EGFR and MAP/ERK kinase (MEK) inhibitors in an effort to gain insight into a novel therapeutic strategy against EGFR WT tumors. Using a panel of human EGFR WT gastric cancer cell lines, we showed that gastric cancer cells harboring the KRAS mutation were selectively sensitive to MEK inhibition as compared with those cells harboring KRAS and PI3K mutations and KRAS WT alleles. However, all cell lines were found to be resistant to EGFR inhibition. The results from Western blots and phosphoprotein arrays showed that, in MEK inhibitor resistant cell lines, AKT was activated through the EGFR/HER3/PI3K pathway following AZD6244 (ARRY-142886) treatment. Blockade of this feedback mechanism through the targeting of MEK and EGFR resulted in detectable synergistic effects in some cell lines in vitro and in vivo. Our results provide the basis for a rational combination strategy against human EGFR WT gastric cancers, predicated on the understanding of cross-talk between the MEK and EGFR pathways. [Mol Cancer Ther 2009;8(9):2526–36]
Stable atrogin-1 (Fbxo32) and MuRF1 (Trim63) gene expression is involved in the protective mechanism in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus)

ABSTRACT Understanding the mechanisms that protect against or limit muscle atrophy in hibernators during prolonged inactivity has important implications for its treatment. We examined whether external factors influence the pathways regulating protein synthesis and degradation, leading to muscle atrophy prevention in Daurian ground squirrels (Spermophilus dauricus). We investigated the effects of 14-day hindlimb-unloading (HU) in different seasons and two-month hibernation on the soleus (SOL) muscle wet mass, muscle-to-body mass ratio, fiber cross sectional area (CSA), fiber distribution and muscle ultrastructure. We also measured changes in the protein expression and activation states of Akt, mTOR and FoxO1 and the mRNA expression of atrogin-1 and MuRF1. Compared with the control groups, autumn and winter HU significantly lowered SOL muscle wet mass and muscle-to-body mass ratio, decreased type I and II fiber CSA and induced ultrastructural anomalies. However, these measured indices were unchanged between Pre-hibernation and Hibernation groups. Furthermore, phosphorylation levels of Akt and mTOR significantly decreased, while the phosphorylation level of FoxO1 and mRNA expression of atrogin-1 and MuRF1 increased after HU. During hibernation, the phosphorylation levels of Akt and mTOR significantly decreased, but the phosphorylation level of FoxO1 and mRNA expression of atrogin-1 and MuRF1 remained unchanged. Overall, our findings suggest that disuse and seasonality may not be sufficient to initiate the innate protective mechanism that prevents SOL atrophy during prolonged periods of hibernation inactivity. The stable expression of atrogin-1 and MuRF1 may facilitate to prevent SOL atrophy via controlling ubiquitination of muscle proteins during hibernation. Summary: mRNA expression of atrogin-1 and MuRF1 remains unchanged during hibernation of Daurian ground squirrels, suggesting that stable expression of these genes may facilitate the prevention of SOL atrophy via controlling ubiquitylation of muscle proteins during hibernation.
Sparse arrays of signatures for online character recognition

In mathematics the signature of a path is a collection of iterated integrals, commonly used for solving dierential equations. We show that the path signature, used as a set of features for consumption by a convolutional neural network (CNN), improves the accuracy of online character recognition|that is the task of reading characters represented as a collection of paths. Using datasets of letters, numbers, Assamese and Chinese characters, we show that the rst, second, and even the third iterated integrals contain useful information for consumption by a CNN. On the CASIA-OLHWDB1.1 3755 Chinese character dataset, our approach gave a test error of 3.58%, compared with 5.61%[4] for a traditional CNN. A CNN trained on the CASIA-OLHWDB1.0-1.2 datasets won the ICDAR2013 Online Isolated Chinese Character recognition competition. Computationally, we have developed a sparse CNN implementation that make it practical to train CNNs with many layers of maxpooling. Extending the MNIST dataset by translations, our sparse CNN gets a test error of 0.31%.
The Role of Silicon in Higher Plants under Salinity and Drought Stress

Although deemed a “non-essential” mineral nutrient, silicon (Si) is clearly beneficial to plant growth and development, particularly under stress conditions, including salinity and drought. Here, we review recent research on the physiological, biochemical, and molecular mechanisms underlying Si-induced alleviation of osmotic and ionic stresses associated with salinity and drought. We distinguish between changes observed in the apoplast (i.e., suberization, lignification, and silicification of the extracellular matrix; transpirational bypass flow of solutes and water), and those of the symplast (i.e., transmembrane transport of solutes and water; gene expression; oxidative stress; metabolism), and discuss these features in the context of Si biogeochemistry and bioavailability in agricultural soils, evaluating the prospect of using Si fertilization to increase crop yield and stress tolerance under salinity and drought conditions.
Cytologic aspect of fibrolamellar hepatocellular carcinoma in fine‐needle aspirates

This is a review of the cytologic and clinicopathological findings seen in a series of six fibrolamellar hepatocellular carcinomas (FL‐HCC) studied by means of fine‐needle aspiration (FNA). A comparison of several cellular measurements (cell, nuclear and nucleolar sizes, and N/C ratios) of FL‐HCC, ordinary hepatocellular carcinoma (O‐HCC), and normal hepatocytes was also carried out in order to find out if these figures could be of help in the cytologic diagnosis. Aspirates were made up of a rather monotonous population of large discohesive cells resembling the morphology of the oncocytes seen in thyroid aspirates; trabecular arrangement of tumor cells was not observed. Cytoplasmic pale bodies and hyaline cytoplasmic bodies were seen in variable quantities. Microbiopsies displaying the fibrolamellar pattern were observed in four cases. FL‐HCC individual tumor cells were larger than individual O‐HCC tumor cells (P < 0.001), as were nuclear (P < 0.007) and nucleolar sizes (P < 0.001), but N/C ratio of O‐HCC was higher than the N/C ratio of FL‐HCC (P < 0.005). Based on the findings, a single cell aspirated from an FL‐HCC is three times the size of a normal hepatocyte and 1.60 times the size of a single cell aspirated from a well‐differentiated O‐HCC. The cytologic findings of FL‐HCC are very characteristic and permit a correct diagnosis of this liver malignancy, provided the cytopathologist is aware of the clinical, demographic, CT‐image, biochemical, and pathological features of this neoplasm. Diagn. Cytopathol. 21:180–187, 1999. © 1999 Wiley‐Liss, Inc.
Echocardiographic parameters of left ventricular size and function as predictors of symptomatic heart failure in patients with a left ventricular ejection fraction of 50-59% treated with anthracyclines.

AIMS The aim of this study was to assess whether baseline echocardiographic measures of left ventricular (LV) size and function predict the development of symptomatic heart failure or cardiac death (major adverse cardiac events, MACE) in patients treated with anthracyclines who have a pre-chemotherapy left ventricular ejection fraction (LVEF) between 50 and 59%. METHODS AND RESULTS Patients with an LVEF between 50 and 59% before anthracyclines were selected. In these patients, LV volumes, LVEF, and peak longitudinal strain (GLS) were measured. Individuals were followed for MACE and all-cause mortality over a median of 659 days (range: 3-3704 days). Of 2234 patients undergoing echocardiography for pre-anthracycline assessment, 158 (7%) had a resting ejection fraction of 50-59%. Their average LV end-diastolic volume (LVEDV) was 101 ± 22 mL, LVEF was 54 ± 3%, and global longitudinal strain (GLS) was -17.7 ± 2.6%. Twelve patients experienced a MACE (congestive heart failure) at a median of 173 days (range: 15-530). Age, diabetes, previous coronary artery disease, LVEDV, indexed LVEDV, LVESV, indexed LVESV, and GLS were all predictive of MACE (P = 0.012, 0.039, 0.0029, 0.012, and 0.0065 for LVEDV, LVEDVI, LVESV, LVESVI, and GLS, respectively). Indexed LVEDV and GLS remained predictive of MACE when adjusted for age. Age and GLS were also predictive of overall mortality (P < 0.0001 and 0.0105, respectively). CONCLUSION In patients treated with anthracyclines with an LVEF of 50-59%, both baseline EDV and GLS predict the occurrence of MACE. These parameters may help target patients who could beneﬁt from closer cardiac surveillance and earlier initiation of cardioprotective medical therapy.
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas

Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review.
epth-Resolved Composition and Electronic Structure of Buried ayers and Interfaces in a LaNiO 3 / SrTiO 3 Superlattice from Soft-and ard-X-ray Standing-Wave Angle-Resolved Photoemission

LaNiO3 (LNO) is an intriguing member of the rare-earth nickelates in exhibiting a metal-insulator transition for a critical film thickness of about 4 unit cells [Son et al., Appl. Phys. Lett. 96, 062114 (2010)]; however, such thin films also show a transition to a metallic state in superlattices with SrTiO3 (STO) [Son et al., Appl. Phys. Lett. 97, 202109 (2010)]. In order to better understand this transition, we have studied a strained LNO/STO superlattice with 10 repeats of [4 unit-cell LNO/3 unit-cell STO] grown on an (LaAlO3)0.3(Sr2AlTaO6)0.7 substrate using soft x-ray standing-wave-excited angle-resolved photoemission (SWARPES), together with softand hardx-ray photoemission measurements of core levels and densities-of-states valence spectra. The experimental results are compared with state-of-the-art density functional theory (DFT) calculations of band structures and densities of states. Using core-level rocking curves and x-ray optical modeling to assess the position of the standing wave, SWARPES measurements are carried out for various incidence angles and used to determine interface-specific changes in momentum-resolved electronic structure. We further show that the momentum-resolved behavior of the Ni 3d eg and t2g states near the Fermi level, as well as those at the bottom of the valence bands, is very similar to recently published SWARPES results for a related La0.7Sr0.3MnO3/SrTiO3 superlattice that was studied using the same technique (Gray et al., ∗ Corresponding author. Present address: Department of Physics, Uppsala University, Uppsala, SE-751 20 Sweden. E-mail addresses: gunnar.palsson@physics.uu.se, gunnar.karl@gmail.com (G.K. Pálsson). 1 Present address: Department of Physics, Temple University, Philadelphia, PA 19122, USA. 2 Present address: Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea. 3 Present address: Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695 USA. 4 Present address: Japan Atomic Energy Agency, Hyogo 679-5148, Japan. ttp://dx.doi. org/10.1016/j.elspec. 2016.04. 008 368-2048/© 2016 Elsevier B.V. All rights reserved. D. Eiteneer et al. / Journal of Electron Spectroscopy and Related Phenomena 211 (2016) 70–81 71 Europhysics Letters 104, 17004 (2013)), which further validates this experimental approach and our conclusions. Our conclusions are also supported in several ways by comparison to DFT calculations for the parent materials and the superlattice, including layer-resolved density-of-states results.
SpaceTag: an overlaid virtual system and its applications

SpaceTag is an object system on which each object called SpaceTag can be accessed only from limited locations and a limited time period. Its applications include entertainment systems, advertisement services, bulletin board systems, and personal communication systems. For one-way communication, they are broadcasted from the server; for two-way communication, users can cut and paste SpaceTags between their portable PCs and the real space. The SpaceTag system is a location-aware information system, as well as an augmented reality system because it attaches information to the real space. However, we categorize it as an overlaid virtual system, because it has no direct link to real objects. It can be realized as a public service without causing drastic change of this society, and without much cost.
The diversity-multiplexing tradeoff of the MIMO Z interference channel

The fundamental diversity-multiplexing tradeoff (DMT) of the quasi-static fading, MIMO Z interference channel (ZIC), with M1 and M2 antennas at the transmitters and N1 and N2 antennas at the corresponding receivers, respectively, is derived. Channel state information at the transmitters (CSIT) and a short-term average power constraint is assumed. The achievability of the DMT is proved by showing that a simple Gaussian superposition coding scheme can achieve a rate region which is within a constant (independent of signal-to-noise ratio (SNR)) number of bits from an upper bound to the capacity region of the ZIC. We also characterize an achievable DMT of the ZIC with No-CSIT and show that in a small region of multiplexing gains (MG), the full CSIT DMT of the ZIC can be achieved with no CSIT at all. The size of this MG region depends on the system parameters such as the number of antennas at the four nodes (referred to hereafter as “antenna configuration”), SNRs and interference-to-noise ratio (INR) of the direct and cross links. Interestingly, for some antenna configurations this MG region covers the entire MG region of the ZIC. Thus, under these circumstances, the optimal DMT of the MIMO ZIC with F-CSIT is same as that of a corresponding ZIC with No-CSIT and availability of CSIT can not further improve the DMT. Finally, we identify a class of ZICs with M1 = M2 = M ≤ N1 over 2, N1 ≤ N2 and SNR ≤ INR where the achievable DMT with No-CSIT coincides with the optimal DMT with F-CSIT.
I fenomeni di flash flood nell'area costiera di Pozzuoli (Napoli, Italia): risultati preliminari sull'analisi dell'evento del 6 novembre 2011

The coastal zone of the Campi Flegrei volcanic district is prone to a wide spectrum of natural hazards, including earthquakes, tsunamis, flash floods, ground deformation, landslides and coastal erosion. In this research we focus on flash flood phenomena occurred in the Pozzuoli catchment, by analyzing historical documents (e.g. newspapers, archive reports, web site news) and integrating the results with daily rain time series of the rain gauge station of Pozzuoli city. In order to understand the evolution of these phenomena, we analyze the 6 November 2011 event that hit the city of Pozzuoli. The study includes the description of meteorological conditions, rainfall properties, ground effects obtained by a web-based research and results obtained simulating flood propagation by means of FLO-2D code. Preliminary results of our research provide a contribution for the understanding of flash floods and flow processes in the study area as well as relevant information for hazard and risk assessment.
Risk factors for anogenital human papillomavirus infection in men.

BACKGROUND Human papillomavirus (HPV) is strongly associated with cervical and other anogenital cancers. Identification of risk factors for HPV infection in men may improve our understanding of HPV transmission and prevention. METHODS HPV testing for 37 types was conducted in 463 men 18-40 years old recruited from 2 US cities. The entire anogenital region and semen were sampled. A self-administered questionnaire was completed. Multivariate logistic regression aided the identification of independent risk factors for any HPV type, oncogenic HPV types, and nononcogenic HPV types. RESULTS Prevalence was 65.4% for any HPV, 29.2% for oncogenic HPV, and 36.3% for nononcogenic HPV. Factors significantly associated with any HPV were smoking > or =10 cigarettes per day (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0-5.3]) and lifetime number of female sex partners (FSPs) (OR for > or =21, 2.5 [95% CI, 1.3-4.6]), and factors significantly associated with oncogenic HPV were lifetime number of FSPs (OR for > or =21, 7.4 [95% CI, 3.4-16.3]) and condom use during the past 3 months (OR for more than half the time, 0.5 [95% CI, 0.3-0.8]). For nononcogenic HPV, a significant association was found for number of FSPs during the past 3 months (OR for > or =2, 2.9 [95% CI, 1.4-6.3]). CONCLUSIONS Lifetime and recent number of FSPs, condom use, and smoking were modifiable risk factors associated with HPV infection in men.
Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation.
A revisit of fault class hierarchies in general boolean specifications

Recently, Kapoor and Bowen [2007] have extended the works by Kuhn [1999], Tsuchiya and Kikuno [2002], and Lau and Yu [2005]. However, their proofs overlook the possibility that a mutant of the Boolean specifications under test may be equivalent. Hence, each of their fault relationships is either incorrect or has an incorrect proof. In this article, we give counterexamples to the incorrect fault relationships and provide new proofs for the valid fault relationships. Furthermore, a co-stronger fault relation is introduced to establish a new fault class hierarchy for general Boolean specifications.
Cost-Utility Analysis of Hepatitis A Prevention Among Health-Care Workers in Israel

This study was conducted to evaluate the efficiency of different strategies of preventing hepatitis A (HA) among physicians, nurses, and paramedical staff by means of cost-effectiveness analysis. The strategies compared were passive immunization during a hepatitis A outbreak, systematic mass vaccination of all workers, and screening for antibodies to HA virus followed by vaccination of nonimmune employees. To predict the prevented number of HA cases, an epidemiological model was incorporated based on our previous nationwide study on clinical HA cases, seroepidemiological survey, and other scientific medical literature. Under the model assumptions, the lowest cost per prevented HA case ($6240) was achieved by screening prior vaccination among 18- to 39-year-old physicians and paramedical workers, and highest ($61,858) by mass vaccination of nurses over age 39 years. Because the price per prevented case may show that mass vaccination is highly cost-effective, especially among 18- to 39-year-old physicians and paramedical workers ($6399 and $8196, respectively), the cost per gained quality-adjusted life-year seems less attractive ($56,532 and $61,350, respectively). This cost per saved quality-adjusted life-year is similar to many other medical interventions but is markedly higher than other primary prevention vaccines, which are mostly associated with a negative ratio. In view of the conducted study, and taking $60,000 as a limit cost per saved quality-adjusted life-year, we propose selective vaccination for physicians and for paramedical workers. Mass vaccination should be offered to all health care workers, aside from nurses 40+ years of age, once the active HA vaccine price is reduced to $23.