Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

Purpose: Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is an effective treatment for patients with KRAS wild-type metastatic colorectal cancer (mCRC), its clinical use is limited by onset of resistance. Experimental Design: We characterized two colorectal cancer models to study the mechanisms of acquired resistance to cetuximab. Results: Following chronic treatment of nude mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival signals were constitutively active despite EGFR inhibition by cetuximab treatment. Whole gene expression profiling identified a series of genes involved in the hepatocyte growth factor (HGF)-MET–dependent pathways, which were upregulated in GEO-CR cells. Furthermore, activated, phosphorylated MET was detected in GEO-CR cells. A second colorectal cancer cell line with acquired resistance to cetuximab was obtained (SW48-CR). Inhibition of MET expression by siRNA restored cetuximab sensitivity in GEO-CR and SW48-CR cells, whereas exogenous activation of MET by HGF stimulation in cetuximab-sensitive GEO and SW48 cells induced resistance to cetuximab. Treatment of GEO-CR and SW48-CR cells with PHA665752, a selective MET inhibitor, inhibited cell growth, proliferation, and survival signals and impaired cancer cell migration. Overexpression of TGF-α, a specific EGFR ligand, was involved in the acquisition of cetuximab resistance in GEO-CR and SW48-CR cells. In fact, TGF-α overexpression induced the EGFR–MET interaction, with subsequent MET phosphorylation and activation of MET downstream effectors in GEO-CR and SW48-CR cells. Conclusions: These results suggest that overexpression of TGF-α through induction of EGFR–MET interaction contributes to cetuximab resistance in colorectal cancer cells. The combined inhibition of EGFR and MET receptor could represent a strategy for preventing and/or overcoming cetuximab resistance in patients with colorectal cancer. Clin Cancer Res; 19(24); 6751–65. ©2013 AACR.
Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new‐onset diabetes: A nationwide cohort study

The effect of diabetes on cirrhosis, its decompensation, and their time relationship in chronic hepatitis C (CHC) patients remains unclear. We conducted a nation‐wide cohort study by using the Taiwanese National Health Insurance Research Database, which is comprised of data from >99% of the entire population. Among having randomly sampled 1 million enrollees, 6,251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in CHC patients who were given the diagnosis in the years 1999‐2003, but not in 1997‐1998. The cohorts of CHC with new‐onset diabetes (n = 424) and nondiabetes (n = 1,708) were followed up from inception point in diabetes and from year 1999 in the nondiabetes cohort until development of cirrhosis or its decompensation, withdrawal from insurance, or December 2009. Kaplan‐Meier's survival analysis showed a significantly higher cumulative incidence of cirrhosis (relative risk [RR] = 1.53; 95% confidence interval [CI] = 1.11‐2.11; log‐rank test; P < 0.001) and decompensated cirrhosis (RR = 2.01; 95% CI = 1.07‐3.79; log‐rank test; P < 0.001) among patients with new‐onset diabetes, as compared to those without. After adjustment for age, gender, CHC treatment, diabetes treatment, hepatocellular carcinoma, comorbidity index, hypertension, hyperlipidemia, and obesity by Cox's proportional hazard model, diabetes was still an independent predictor for cirrhosis (hazard ratio [HR] = 2.505; 95% CI = 1.609‐3.897; P < 0.001) and its decompensation (HR = 3.560; 95% CI = 1.526‐8.307; P = 0.003). Conclusion: CHC patients who develop diabetes are at an increased risk of liver cirrhosis and its decompensation over time. (Hepatology 2014;60:807–814)
Topography of neovascularity in human prostate carcinoma

Background. All neoplasms require angiogenesis and resulting neovascularity for growth. The authors and others have confirmed the staging and prognostic significance of quantitative microvascularity density (MVD) in human prostate carcinoma (CAP). In the present investigation, the authors sought to identify the specific site of neovascularity within the neoplasm and adjacent benign tissue.
Eight Conflict Handling Styles: Validation of Model and Instrument

Eight conflict handling styles emerged as statistically unidimensional in the development of this new model: avoiding/smoothing, obliging, integrating, compromising, dominating, coercing, deceiving, and ingratiating. Scales for these styles were tested for construct validity in dyadic conflict scenarios among peers. Preference for styles were found to vary according to (1) independent and interdependent self-construals, (2) ingroup or outgroup membership, and (3) benefit-issue. Independence correlated positively with integrating and compromising, and negatively with coercion and deception. Interdependence correlated positively with avoiding/smoothing, obliging, compromising, deception, and ingratiation. Subjects were more obliging, integrating, and compromising toward ingroup than outgroup members; and slightly more coercive and deceptive with outgroup than ingroup members. Subjects were more deceptive in other-benefiting issue situations than in self-benefiting ones.
An ADMM algorithm for solving a proximal bound-constrained quadratic program

We consider a proximal operator given by a quadratic function subject to bound constraints and give an optimization algorithm using the alternating direction method of multipliers (ADMM). The algorithm is particularly efficient to solve a collection of proximal operators that share the same quadratic form, or if the quadratic program is the relaxation of a binary quadratic problem.
Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells.
New Insights into the Diversity of Marine Picoeukaryotes

Over the last decade, culture-independent surveys of marine picoeukaryotic diversity based on 18S ribosomal DNA clone libraries have unveiled numerous sequences of novel high-rank taxa. This newfound diversity has significantly altered our understanding of marine microbial food webs and the evolution of eukaryotes. However, the current picture of marine eukaryotic biodiversity may be significantly skewed by PCR amplification biases, occurrence of rDNA genes in multiple copies within a single cell, and the capacity of DNA to persist as extracellular material. In this study we performed an analysis of the metagenomic dataset from the Global Ocean Survey (GOS) expedition, seeking eukaryotic ribosomal signatures. This PCR-free approach revealed similar phylogenetic patterns to clone library surveys, suggesting that PCR steps do not impose major biases in the exploration of environmental DNA. The different cell size fractions within the GOS dataset, however, displayed a distinct picture. High protistan diversity in the <0.8 µm size fraction, in particular sequences from radiolarians and ciliates (and their absence in the 0.8–3 µm fraction), suggest that most of the DNA in this fraction comes from extracellular material from larger cells. In addition, we compared the phylogenetic patterns from rDNA and reverse transcribed rRNA 18S clone libraries from the same sample harvested in the Mediterranean Sea. The libraries revealed major differences, with taxa such as pelagophytes or picobiliphytes only detected in the 18S rRNA library. MAST (Marine Stramenopiles) appeared as potentially prominent grazers and we observed a significant decrease in the contribution of alveolate and radiolarian sequences, which overwhelmingly dominated rDNA libraries. The rRNA approach appears to be less affected by taxon-specific rDNA copy number and likely better depicts the biogeochemical significance of marine protists.
A video forensic technique for detecting frame deletion and insertion

We propose a method for detecting insertion and deletion of whole frames in digital videos. We start by strengthening and extending a state of the art method for double encoding detection, and propose a system that is able to locate the point in time where frames have been deleted or inserted, discerning between the two cases. The proposed method is applicable even when different codecs are used for the first and second compression, and performs well even when the second encoding is as strong as the first one.
The susceptibility of milked and unmilked udder quarters to intra-mammary infection

Summary The teats of quarters which were milked, and those in which milking had ceased, of 16 cows were exposed to bacteria twice daily for 2 weeks by dipping them in a suspension of streptococci and staphylococci. Of 32 quarters in which milking had ceased 22 became infected in this period. Eighteen infections were with Streptococcus dysgalactiae, 2 with Streptococcus uberis, 1 with Staphylococcus aureus and 2 with organisms not used in the culture. Only 3 of 32 milked quarters became infected in the experimental period: 2 infections were with Str. aureus and 1 with an organism not used in the culture. Animals differed in their susceptibility to infection. Quarters which had been unmilked for 2 weeks were as susceptible to new infectionas those in which milking had just ceased. In this experiment, factors such as intramammary pressure, leakage of milk, concentration of bacterial inhibitors, composition of secretion and cell counts of the secretion did not appear to influence the rate of infection. Yield at drying-off, milking rates and teat patency were not related to the differences in susceptibility between animals. It is suggested that the main reason for the lower new infection rate in the milked quarters is that pathogens entering the streak canal or teat sinus are usually flushed out with the secretion during milking and do not cause infection.
An Organizational Impression Management Perspective on the Formation of Corporate Reputations

Researchers have only recently turned their attention to the study of corporate reputation.As is characteristic of many early areas of management inquiry, the field is decidedly multidisciplinary and disconnected. This article selectively reviews reputation research conducted mainly during the past decade. A framework is proposed that views reputation from the perspective of organizational impression management. Corporations are viewed as social actors, intent on enhancing their respectability and impressiveness in the eyes of constituents.
A Relative Privacy Model for Effective Privacy Preservation in Transactional Data

Transactional data such as shopping logs, web search queries and medical notes present enormous opportunities for knowledge discovery through data mining. When such data is published for knowledge discovery, privacy disclosure risks arise, making privacy preserving publication a fundamental requirement. However, existing publication mechanisms do not fully prevent an adversary from making an inference about the intended victim. While some solutions to this problem exist for the publication of relational data, they are not transferable to the publication of transactional data due to the difference in data models. This work aims to prevent inference attacks in the publication of transactional data by proposing a relative privacy metric that ensures that the knowledge gain of an adversary about any individual from the published data is bound to the general public knowledge. We then propose a publication mechanism Anony, which satisfies the proposed privacy metric without having to use excessively large cluster sizes. Finally, we evaluate our publication mechanism using two benchmark datasets and the results demonstrate that the proposed mechanism is effective and efficient.
Image resizing and rotation based on the consistent resampling theory

The recently proposed consistent resampling theory for non-bandlimited signals is applied to image resizing and rotation. Images with high frequency components can be resampled using this scheme to achieve high quality performance. Image resizing is treated as resampling using non-ideal interpolation functions. Both zoom in and zoom out by non-integer factors are considered. Image rotation is also formulated as a resampling process. We show that our approach outperforms other linear image processing techniques without increasing the computational cost.
Implementation of Health Information System-A Case Study of Magrabi Hospitals, KSA

Today's healthcare market has created its niche by adopting emerging technologies and ensuring minimal rate of failures. Embracing integrated Health Information System (HIS) is one such venture that not only helps the organization to excel in the market but also caters to the needs of the public. The present research paper is a case study of HIS implementation of Magrabi hospitals and centres, in Saudi Arabia. Though implementing HIS is a herculean task, with respect to the efforts as well as investment, Magrabi could achieve this task with at most care. The system could promote service efficacy across all the centres and hospitals of Magrabi. The paper analyses the procedures and strategies followed in order to prepare the entity ready for transformation. That is, the method of actualizing the health system implementation is also detailed in this study. Overall, the case research tried to know the extent of improvement took place in all the streams of operations in Magrabi group after automation. To gather this information, data is collected from all the in-charges of respective departments as well as users, who are in managerial cadre. This data is tabulated against various cycles (revenue and payroll). From the opinion of the stakeholders it can be easily understood that HIS has brought a sea change in the service flows of Magrabi group. Apart from the benefits of HIS implementation, the lacunae of the study along with the future research prospects in these lines are suggested for the possible improvements.
Plasmids survive despite their cost and male-specific phages due to heterogeneity of bacterial populations

Problem: Conjugative plasmids manipulate their bacterial hosts to express sex-pili – long, filamentous organelles whose genes are carried by the plasmids themselves. Sex-pili locate and attach to another bacterial cell for plasmid transfer. Bacteria differ in their ability to express sex-pili and hence to donate plasmids. Does this diversity in sex-pilus expression contribute to the survival of conjugative plasmids? Method: Simulations of a chemostat containing bacterial cells, some harbouring a conjugative plasmid. Certain viruses, called male-specific phages (MSPs), enter the chemostat. These viruses infect only donor cells. I monitor whether plasmids continue to survive in each simulation. Key assumption: A bacterium’s ability to donate is proportional to its susceptibility to MSPs. Conclusions: Bacterial diversity in sex-pilus expression strongly increases the size of the parameter space for plasmid survival. A host with low expression of sex-pili – and hence a low plasmid transfer rate – represents a sink habitat for the conjugative plasmid. However, hosts with high expression of sex-pili also constitute sink habitats – although they have a high plasmid transfer rate, they are the most susceptible to MSPs. A system consisting of both types of bacteria (two sink habitats) constitutes a source habitat for the conjugative plasmid. At the same time, this diversity helps to maintain the MSP itself because extinction of the conjugative plasmids would also doom the MSP.
Provision of Contraceptive Services to Homeless Women: Results of a Survey of Health Care for the Homeless Providers

Homeless women have both a higher rate of pregnancy and a higher proportion of unintended pregnancies than other American women. The authors sought to learn about contraception services offered by providers of health care to homeless women and barriers to provision of long-acting, reversible contraception in these settings. A survey of the 31 member organizations in the national Health Care for the Homeless Practice-Based Research Network was conducted, inquiring about services provided and barriers to service provision. Among the 20 responding organizations (65% response rate), 17 directly provided contraceptive services; two referred patients elsewhere, and one provided no contraceptive services. All 17 that provided such services provided condoms; 15 provided oral contraceptives; 14 provided injectable contraception; 6 provided intrauterine devices, and 2 provided contraceptive implants. Barriers to providing the last two methods included lack of provider training, lack of resources for placement, costs, and concerns about complications. The present survey results suggested very limited access for homeless women across the country to the two most effective means of long-acting, reversible contraception. Modest investments of resources could reduce a number of barriers to providing these services.
Role of monokine induced by interferon‐γ in liver injury induced by hepatitis B virus in mice

Summary. The chemokine monokine induced by interferon‐γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)‐κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome‐containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad‐HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF‐κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3‐kinase/Akt, extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo‐jetPEI‐Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF‐κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3‐kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.
FINDING SONGS THAT SOUND THE SAME

A crucial dimension of Content-based music management systems is their ability to compute automatically similarities be tween music titles. We propose a technique that allows users to find mu sic titles that sound similar to songs they like. The technique relies on a modelling of the timbral characteristics of a music s ignal by distributions of Cepstrum coefficients. The resulting model s are then compared to yield a similarity measure. The paper desc ribes the algorithm, and proposes an evaluation of the quality of t he extracted similarity measure. Additionally, we illustra te the use of this measure in two Electronic Music Distribution applica tions developed in the context of the European project Cuidado.
Microarray Analysis of Defective Cartilage in Hoxc8- and Hoxd4-Transgenic Mice

Objective: Homeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxc8 and Hoxd4 during cartilage development, the authors observed severe defects, namely, physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, the authors performed gene expression profiling using the Affymetrix microarray platform. Results: Primary chondrocytes were isolated from Hoxc8- and Hoxd4-transgenic mouse embryo rib cartilage at 18.5 days of gestation. In both cases, differentially expressed genes were identified that have a role in cell proliferation and cell cycle regulation. A comparison between the controls for both experimental groups did not reveal significant differences, as expected. However, the repertoires of differentially expressed genes were found not to overlap between Hoxc8- and Hoxd4-transgenic cartilage. This included different Wnt genes, cell cycle, and apoptosis regulators. Conclusion: Overexpression of Hoxc8 and Hoxd4 transcription factors alters transcriptional profiles in chondrocytes at E18.5. The differences in repertoires of altered gene expression between the 2 transgenic conditions suggest that the molecular mechanisms underlying the cartilage defects may be different in both transgenic paradigms, despite apparently similar phenotypes.
Genetic variation among lambs in peripheral IgE activity against the larval stages of Teladorsagia circumcincta

SUMMARY IgA and IgE activity against Teladorsagia circumcincta was investigated in a flock of Texel lambs following natural, mixed nematode infection among lambs. The distribution of IgA activity was similar to a gamma distribution whereas IgE activity was different. Box-Cox analysis demonstrated that X0·25 was a suitable transformation to normalise IgE responses. The transformed IgE activity was under moderate to strong genetic control. Nine different allergens were identified by proteomic analysis. Tropomyosin was selected for further analysis. IgE activity against tropomyosin was moderately heritable and associated with decreased egg counts and with reduced body weight at the time of sampling.