Miracle-dz/UniFAR-FTUs huggingface dataset:
Induced IGF-1 R activation contributes to gefitinib resistance following combined treatment with paclitaxel , cisplatin and gefitinib in A 549 lung cancer cells

Gefitinib demonstrates excellent performance in the treatment of lung adenocarcinoma patients; yet, there was no added benefit in combination with chemotherapy as reported in a phase III clinical trial. For exploring the mechanism of the failed combination therapy in lung cancer, in the present study, four therapy assessment groups, including a control group, a chemotherapy group [paclitaxel + cisplatin (TP)], a gefitinib monotherapy group (G) and a combination group [paclitaxel + cisplatin + gefitinib (TP+G)], were established in an A549 cell line and mouse xenotransplanted tumor models. By HPLC, we found that the gefitinib concentration was significantly higher in the combination group when compared to that in the G group in the non-small cell lung cancer cell line, A549 (p<0.05). Following the treatment time extension, an increased cell growth rate was observed in the combination group, while the cellular concentration of gefitinib was not decreased. The expression levels of P-IGF-1R, P-SRC and P-ERK in the fourth combination treatment group were significantly higher than levels in the fourth G treatment and control groups (p<0.05). Following downregulating of IGF-1R in the fourth combination treatment group, drug sensitivity was recovered in vitro. In the mouse model, compared with the gefitinib monotherapy group, the combination group exhibited a smaller tumor volume, lower body weight and reduced survival rate (p<0.05). Gefitinib concentrations in the serum and tumor tissues in the combination therapy group were also decreased when compared with these concentrations in the gefitinib alone group. The present study is the first to demonstrate that the decreased gefitinib concentration in serum and tumor tissues is one of the reasons resulting in the failed combination treatment (chemotherapy + gefitinib) in vivo study. Frequent use of the combination treatment in A549 lung cancer cells induced IGF-1R activation which contributed to gefitinib resistance and gave rise to the failure of the combination therapy.
CFD-Based Operational Thermal Efficiency Improvement of a Production Data Center

Effective cooling of data centers presents a dual challenge: increased cooling power to meet the ever increasing device heat loads, and the need for energy efficient cooling. Detailed analysis of the thermal and flow conditions within a data center are necessary for obtaining optimal design and operational parameters. This paper describes the application of a computational fluid dynamics (CFD) based model in a production data center for improving its operational efficiency. The model used in the present work is based on conjugate heat transfer and fluid flow at data center level. The effect of heat dissipation from racks, and thermal and flow conditions at perforated tiles are bought into the model through boundary conditions. The model is rigorously validated by comparing simulation results with actual measurements. Extensive parametric studies have been performed, and key issues, resulting in mixing and ineffective cooling, have been identified. Several design and operational changes have been recommended in terms of placement of blanking panels, operation of CRAC units, and operating set-points. These recommendations have been implemented at the data center, resulting in energy savings to the tune of 20%. Further, the model has been used extensively for obtaining guidelines for efficient ramping up of the data center.
Activation of Notch Signaling Is Required for Cholangiocarcinoma Progression and Is Enhanced by Inactivation of p53 In Vivo

Cholangiocacinoma (CC) is a cancer disease with rising incidence. Notch signaling has been shown to be deregulated in many cancers. However, the role of this signaling pathway in the carcinogenesis of CC is still not fully explored. In this study, we investigated the effects of Notch inhibition by γ-secretase inhibitor IX (GSI IX) in cultured human CC cell lines and we established a transgenic mouse model with liver specific expression of the intracellular domain of Notch (Notch-ICD) and inactivation of tumor suppressor p53. GSI IX treatment effectively impaired cell proliferation, migration, invasion, epithelial to mesenchymal transition and growth of softagar colonies. In vivo overexpression of Notch-ICD together with an inactivation of p53 significantly increased tumor burden and showed CC characteristics. Conclusion: Our study highlights the importance of Notch signaling in the tumorigenesis of CC and demonstrates that additional inactivation of p53 in vivo.
Public Attitudes toward Immigration in the United States, France, and Germany

1. Marginality, economic self-interest, and contact Part I. Historical Analysis: 2. History of attitudes toward immigration in the United States 3. History of attitudes toward immigration in France 4. History of attitudes toward immigration in Germany Part II. Quantitative Analysis: 5. Over-time opposition to immigration and support for nativist political movements 6. Recent attitudes toward immigration in the United States 7. Recent attitudes toward immigration in France 8. Recent attitudes toward immigration in Germany 9. Culture, nationality, and the future of nativism.
Alteration of the Repressor Activity of MarR, the Negative Regulator of the Escherichia coli marRAB Locus, by Multiple Chemicals In Vitro

ABSTRACT MarR negatively regulates expression of the multiple antibiotic resistance operon (marRAB) in Escherichia coli. In this study, it was demonstrated that sodium salicylate, plumbagin, 2,4-dinitrophenol, and menadione–inducers of the marRABoperon in whole cells–all interfered with the repressor activity of MarR in vitro. It is proposed that these compounds can interact directly with MarR to affect its repressor activity.
The Information Content of Forward and Futures Prices: Market Expectations and the Price of Risk

Forward and futures rates are frequently used as measures of market expectations. In this paper we apply standard forecast efficiency tests, and some newer exact sign and rank tests, to a wide range of forward and futures rates, and in this way test whether these are in fact rational expectations of future actual prices. The forward and futures rates that we study under a common methodology include foreign exchange forward rates, U.S. and foreign interest rate futures and forward rates, oil futures and natural gas futures. For most, but not all, of these instruments, we find that we can reject the hypothesis that the forward or futures rates are rational expectations of actual future prices. It is well known that foreign exchange forward rates give less accurate forecasts than a random walk, but we show that this is also true for some interest rate futures and forward rates. We conclude that forward and futures prices are not generally pure measures of market expectations: they are also heavily affected by the market price of risk.
How Patients Contribute to an Online Psychoeducation Forum for Bipolar Disorder: A Virtual Participant Observation Study

Background In a recent exploratory randomized controlled trial, an online psychoeducation intervention for bipolar disorder has been found to be feasible and acceptable to patients and may positively impact on their self-management behaviors and quality of life. Objective The objective of the study was to investigate how these patients contribute to an online forum for bipolar disorder and the issues relevant for them. Methods Participants in the intervention arm of the Bipolar Interactive PsychoEDucation (“BIPED”) trial were invited to contribute to the Beating Bipolar forum alongside receiving interactive online psychoeducation modules. Within this virtual participant observation study, forum posts were analyzed using thematic analysis, incorporating aspects of discourse analysis. Results The key themes which arose from the forum posts included: medication, employment, stigma, social support, coping strategies, insight and acceptance, the life chart, and negative experiences of health care. Participants frequently provided personal narratives relating to their history of bipolar disorder, life experiences, and backgrounds, which often contained emotive language and humor. They regularly sought and offered advice, and expressed encouragement and empathy. The forum would have benefitted from more users to offer a greater support network with more diverse views and experiences. Conclusions Online forums are inexpensive to provide and may offer peer support and the opportunity for patients to share their experiences and explore issues related to their illness anonymously. Future research should focus on how to enhance patient engagement with online health care forums. Trial Registration ISRCTN81375447; http://www.isrctn. com/ISRCTN81375447 (Archived by WebCite at http://www.webcitation.org/6YzWtHUqu).
Radio Continuum Surveys with Square Kilometre Array Pathfinders

Abstract In the lead-up to the Square Kilometre Array (SKA) project, several next-generation radio telescopes and upgrades are already being built around the world. These include APERTIF (The Netherlands), ASKAP (Australia), e-MERLIN (UK), VLA (USA), e-EVN (based in Europe), LOFAR (The Netherlands), MeerKAT (South Africa), and the Murchison Widefield Array. Each of these new instruments has different strengths, and coordination of surveys between them can help maximise the science from each of them. A radio continuum survey is being planned on each of them with the primary science objective of understanding the formation and evolution of galaxies over cosmic time, and the cosmological parameters and large-scale structures which drive it. In pursuit of this objective, the different teams are developing a variety of new techniques, and refining existing ones. To achieve these exciting scientific goals, many technical challenges must be addressed by the survey instruments. Given the limited resources of the global radio-astronomical community, it is essential that we pool our skills and knowledge. We do not have sufficient resources to enjoy the luxury of re-inventing wheels. We face significant challenges in calibration, imaging, source extraction and measurement, classification and cross-identification, redshift determination, stacking, and data-intensive research. As these instruments extend the observational parameters, we will face further unexpected challenges in calibration, imaging, and interpretation. If we are to realise the full scientific potential of these expensive instruments, it is essential that we devote enough resources and careful study to understanding the instrumental effects and how they will affect the data. We have established an SKA Radio Continuum Survey working group, whose prime role is to maximise science from these instruments by ensuring we share resources and expertise across the projects. Here we describe these projects, their science goals, and the technical challenges which are being addressed to maximise the science return.
Recent advances in least squares 3D surface matching

We present an algorithm for the least squares matching of overlapping 3D surfaces. It estimates the transformation parameters between two or more fully 3D surfaces, using the Generalized Gauss-Markoff model, minimizing the sum of squares of the Euclidean distances between the surfaces. This formulation gives the opportunity of matching arbitrarily oriented 3D surfaces simultaneously, without using explicit tie points. Besides the mathematical model of the procedure, we discuss the computational aspects. We give practical examples to demonstrate the method.
ffi cient and Tailored Resource Management for the P 2 P Web Caching

While web proxy caching is a widely deployed technique, the performance of a proxy cache is limited by the local storage. Some studies have addressed this limitation by using the residual resources of clients via a p2p method and have achieved a very high hit rate. However, these approaches treat web objects as homogeneous objects and there is no consideration of various web characteristics. Consequently, the byte hit rate of the system is limited, external bandwidth is wasted, and perceived user latency is increased. The present paper suggests an efficient p2p based web caching technique that manages objects with different policies so as to exploit the characteristics of web objects, such as size and temporal locality. Small objects are stored alone whereas large objects are stored by dividing them into numerous small blocks, which are distributed in clients. On a proxy cache, header blocks of large objects take the place of objects themselves and smaller objects are cached. This technique increases the hit rate. Unlike a web cache, which evicts large objects as soon as possible in the case where clients fulfill the role of backup storage, large objects are given higher priority than small objects in the proposed approach. This maximizes the effect of hits for large objects and thereby increases the byte hit rate. Furthermore, we construct simple latency models for various p2p based web caching systems and analyze the effects of the proposed policies on these systems. We then examine the performances of the efficient policies via a trace driven simulation. The results demonstrate that the proposed techniques effectively enhance web cache performance, including hit rate, byte hit rate, and response time. key words: peer-to-peer, Web caching, replacement algorithm
Hominoid-Specific De Novo Protein-Coding Genes Originating from Long Non-Coding RNAs

Tinkering with pre-existing genes has long been known as a major way to create new genes. Recently, however, motherless protein-coding genes have been found to have emerged de novo from ancestral non-coding DNAs. How these genes originated is not well addressed to date. Here we identified 24 hominoid-specific de novo protein-coding genes with precise origination timing in vertebrate phylogeny. Strand-specific RNA–Seq analyses were performed in five rhesus macaque tissues (liver, prefrontal cortex, skeletal muscle, adipose, and testis), which were then integrated with public transcriptome data from human, chimpanzee, and rhesus macaque. On the basis of comparing the RNA expression profiles in the three species, we found that most of the hominoid-specific de novo protein-coding genes encoded polyadenylated non-coding RNAs in rhesus macaque or chimpanzee with a similar transcript structure and correlated tissue expression profile. According to the rule of parsimony, the majority of these hominoid-specific de novo protein-coding genes appear to have acquired a regulated transcript structure and expression profile before acquiring coding potential. Interestingly, although the expression profile was largely correlated, the coding genes in human often showed higher transcriptional abundance than their non-coding counterparts in rhesus macaque. The major findings we report in this manuscript are robust and insensitive to the parameters used in the identification and analysis of de novo genes. Our results suggest that at least a portion of long non-coding RNAs, especially those with active and regulated transcription, may serve as a birth pool for protein-coding genes, which are then further optimized at the transcriptional level.
Malarial Pigment Hemozoin and the Innate Inflammatory Response

Malaria is a deadly infectious disease caused by the intraerythrocytic protozoan parasite Plasmodium. The four species of Plasmodium known to affect humans all produce an inorganic crystal called hemozoin (HZ) during the heme detoxification process. HZ is released from the food vacuole into circulation during erythrocyte lysis, while the released parasites further infect additional naive red blood cells. Once in circulation, HZ is rapidly taken up by circulating monocytes and tissue macrophages, inducing the production of pro-inflammatory mediators, such as interleukin-1β (IL-1β). Over the last few years, it has been reported that HZ, similar to uric acid crystals, asbestos, and silica, is able to trigger IL-1β production via the activation of the NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome complex. Additionally, recent findings have shown that host factors, such as fibrinogen, have the ability to adhere to free HZ and modify its capacity to activate host immune cells. Although much has been discovered regarding NLRP3 inflammasome induction, the mechanism through which this intracellular multimolecular complex is activated remains unclear. In the present review, the most recent discoveries regarding the capacity of HZ to trigger this innate immune complex as well as the impact of HZ on several other inflammatory signaling pathways will be discussed.
UNSUPERVISED ANOMALY DETECTION IN LARGE DATABASES USING BAYESIAN NETWORKS

Today, there has been a massive proliferation of huge databases storing valuable information. The opportunities of an effective use of these new data sources are enormous; however, the huge size and dimensionality of current large databases calls for new ideas to scale up current statistical and computational approaches. This article presents an application of artificial intelligence technology to the problem of automatic detection of candidate anomalous records in a large database. We build our approach with three main goals in mind: 1) an effective detection of the records that are potentially anomalous; 2) a suitable selection of the subset of attributes that explains what makes a record anomalous; and 3) an efficient implementation that allows us to scale the approach to large databases. Our algorithm, called Bayesian network anomaly detector (BNAD), uses the joint probability density function (pdf) provided by a Bayesian network (BN) to achieve these goals. By using appropriate data structures, advanced caching techniques, the flexibility of Gaussian mixture models, and the efficiency of BNs to model joint pdfs, BNAD manages to efficiently learn a suitable BN from a large dataset. We test BNAD using synthetic and real databases, the latter from the fields of manufacturing and astronomy, obtaining encouraging results.
Constitutive Curve and Velocity Profile in Entangled Polymers during Start-Up of Steady Shear Flow

Time-dependent shear stress versus shear rate, constitutive curve, and velocity profile measurements are reported in entangled polymer solutions during start-up of steady shear flow. By combining confocal microscopy and particle image velocimetry (PIV), we determine the time-dependent velocity profile in polybutadiene and polystyrene solutions seeded with fluorescent 150 nm silica and 7.5 μm melamine particles. By comparing these profiles with time-dependent constitutive curves obtained from experiment and theory, we explore the connection between transient nonmonotonic regions in the constitutive curve for an entangled polymer and its susceptibility to unstable flow by shear banding (Adams et al. Phys. Rev. Lett. 2009, 102, 067801-4). Surprisingly, we find that even polymer systems which exhibit transient, nonmonotonic shear stress-shear rate relationships in bulk rheology experiments manifest time-dependent velocity profiles that are decidedly linear and show no evidence of unstable flow. We also report that interfacial slip plays an important role in the steady shear flow behavior of entangled polymers at shear rates above the reciprocal terminal relaxation time but has little, if any, effect on the shape of the velocity profile.
CEP Discussion Paper No 1085 November 2011 Heterogeneous Firm-Level Responses to Trade Liberalisation : A Test Using Stock Price Reactions

This paper presents novel empirical evidence on key predictions of heterogeneous firm models by examining stock market reactions to the Canada-United States Free Trade Agreement of 1989 (CUSFTA). Using the uncertainty surrounding the agreement’s ratification, I show that the pattern of abnormal returns of Canadian manufacturing . firms was broadly consistent with the predictions of a class of models based on Melitz (2003). Increases in the likelihood of ratification led to stock market gains of exporting firms relative to non-exporters. Moreover, gains were higher in sectors with larger cuts in U.S. import tariffs. Decreases in the likelihood of ratification led to opposite stock market reactions. Results for the impact of Canadian tariff reductions are less conclusive but most specifications suggest that exporters also gained relative to non-exporters in response to such reductions. Translating stock market gains into implied profit changes, I find that CUSFTA increased expected per-period profits of exporters by around 6-7% relative to non-exporters.
The Impact of Losses and Cash Flows on Dividends: Empirical Evidence for Japan

The article's purpose is to examine the impact of cash flows, earnings, and losses in setting dividend policy in Japan. More specifically, i) earnings, cash flows and annual losses are posited to be associated with dividend changes in firms with established earnings and dividend records; and ii) dividend reductions, current operating earnings and cash flows have information content in predicting future earnings. The results here support these hypotheses. Moreover, annual losses are shown to be a necessary but not a sufficient condition for dividend reductions in firms with established earnings and dividend records. About 80% of the 191 Japanese firms that reported losses during the period 1990-94 reduced or omitted dividends. In contrast, only 16% of the 338 firms that did not report losses during the same period reduced dividends.
Association and release of the amyloid protein precursor of Alzheimer's disease from chick brain extracellular matrix

The amyloid protein precursor (APP) of Alzheimer's disease was found to bind saturably (Kd = 60 nM) to embryonic chick brain extracellular matrix (ECM). The binding of APP to ECM was not inhibited by 10 micrograms/ml heparin or heparan sulfate. However, pretreatment of cells with 1 mM 4-methylumbelliferyl-beta-D-xyloside, an inhibitor of proteoglycan biosynthesis, reduced the number of APP binding sites on the ECM by 80%. The binding of APP to ECM was also inhibited by pretreatment with chlorate, an inhibitor of glycan sulfation, and heparitinase, which digests the carbohydrate component of heparan sulfate proteoglycans. These results suggest that APP binds with high affinity to one or more heparan sulfate proteoglycans. Acidic and basic fibroblasts growth factor (FGF) also bound to chick ECM. When ECM was incubated with a protease associated with the enzyme AChE (AChE-AP), APP and acidic FGF were released intact from the matrix. The AChE-AP was at least 100-fold more potent in releasing APP from ECM than other trypsin-like proteases (trypsin, plasmin, thrombin). The action of the AChE-AP was inhibited by glia-derived nexin (protease nexin I) and by human brain APP at low nanomolar concentrations. These results suggest that in vivo an AChE-AP may cleave ECM proteins to regulate the availability of soluble APP or other factors bound to the ECM.
The influence of group membership on the neural correlates involved in empathy

Empathy involves affective, cognitive, and emotion regulative components. The affective component relies on the sharing of emotional states with others and is discussed here in relation to the human Mirror System. On the other hand, the cognitive component is related to understanding the mental states of others and draws upon literature surrounding Theory of Mind (ToM). The final component, emotion regulation, depends on executive function and is responsible for managing the degree to which explicit empathic responses are made. This mini-review provides information on how each of the three components is individually affected by group membership and how this leads to in-group bias.