Miracle-dz/UniFAR-FTUs huggingface dataset:
Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR‐mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFRT790M mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, combined with EGFR‐TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975‐harboring EGFRL858R+T790M and RPC‐9‐harboring EGFR19DEL+T790M, we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC‐9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31‐positive vascular endothelial cells and increased cleaved caspase‐3‐positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFRT790M mutations. Therefore, clinical trials of this combination therapy are warranted.
Cis‐regulator runaway and divergence in asexuals

With the advent of new sequencing technologies, the evolution of gene expression is becoming a subject of intensive genomic research, with sparking debates upon the role played by these kinds of changes in adaptive evolution and speciation. In this article, we model expression evolution in species differing by their reproductive systems. We consider different rates of sexual versus asexual reproduction and the different type of parthenogenesis (apomixis and the various modes of automixis). We show that competition for expression leads to two selective processes on cis‐regulatory regions that act independently to organism‐level adaptation. Coevolution within regulatory networks allows these processes to occur without strongly modifying expression levels. First, cis‐regulatory regions such as enhancers evolve in a runaway fashion because they automatically become associated to chromosomes purged from deleterious mutations (“Enhancer Runaway process”). Second, in clonal or nearly clonal species, homologous cis‐regulatory regions tend to diverge, which leads to haploidization of expression, when they are sufficiently isolated from one another (“Enhancer Divergence process”). We show how these two processes cooccur and vary depending on the level of outcrossing, gene conversion, mitotic recombination, or recombination in automictic species. This study offers thus a baseline to understand patterns of expression evolution across the diversity of eukaryotic species.
Surface modification of Ti6Al4 V implants by heat, H2O2 and alkali treatments

In the present research we have applied three types of surface modifications on Ti6Al4 V alloy including heat treatment, H2O2 treatment and alkali treatment. Scanning electron microscope and thin-film X-ray diffractometry (TF-XRD) were used to analyse the surface structure and the formed phases on the surface modified specimens. In vitro bioactivity evaluations were carried out and the cytocompatibility assay was performed using the evaluation of viability and attachment of L-929 fibroblast cells. The results revealed more bioactivity of the alkali-treated Ti6Al4 V alloy compared to other surface modifications. Better cellular response was also observed on the alkali-treated specimens. According to the results of our study, alkali treatment enhanced the in vitro bioactivity and cytocompatibility of Ti6Al4 V alloy more effectively than H2O2 treatment and heat treatment.
Social Environment Affects Acquisition and Color of Structural Nuptial Plumage in a Sexually Dimorphic Tropical Passerine

Structural colors result from the physical interaction of light with organic materials of differing refractive indexes organized at nanoscale dimensions to produce significant interference effects. Because color properties emerge from these finely organized nanostructures, the production of structural coloration could respond to environmental factors and be developmentally more plastic than expected, functioning as an indicator of individual quality. However, there are many unknown factors concerning the function and mechanisms regulating structural coloration, especially relative to social environment. We hypothesized that social environment, in the form of competitive settings, can influence the developmental pathways involving production of feather structural coloration. We experimentally assessed the impact of social environment upon body condition, molt and spectral properties of two types of structural color that compose the nuptial plumage in blue-black grassquits: black iridescent plumage and white underwing patches. We manipulated male social environment during nine months by keeping individuals in three treatments: (1) pairs; (2) all-male groups; and (3) male-female mixed groups. All morphological characters and spectral plumage measures varied significantly through time, but only acquisition of nuptial plumage coverage and nuptial plumage color were influenced by social environment. Compared with males in the paired treatment, those in treatments with multiple males molted into nuptial plumage faster and earlier, and their plumage was more UV-purple-shifted. Our results provide experimental evidence that social context strongly influences development and expression of structural plumage. These results emphasize the importance of long-term experimental studies to identify the phenotypic consequences of social dynamics relative to ornament expression.
Dissection of Regulatory Elements During Direct Conversion of Somatic Cells Into Neurons

A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes, and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease. However, early successful experiments followed by major drawbacks such as low differentiation efficiency in producing neurons and detection of various undesirable types of cells in the culture. Therefore, there is not a single optimized common protocol for producing high quality neurons in vitro so far. This is partly due to the lack of our understanding about the precise cellular, genetic, and molecular mechanisms underlying neurogenesis via direct conversion. In the current work, we have employed meta‐analysis tools and extensive gene regulatory network analysis on the high throughput gene expression data obtained from previous reprogramming protocols to identify central gene regulatory components involved in direct conversion of fibroblasts into neurons. Our results identified miR‐9, miR‐30 as the most important miRNA and TP53, MYC, JUN, SP1, and SMAD2 considered to be the most important transcription factors. These findings would be useful for direct targeting these hub regulatory elements in order to increase the efficacy and specificity of the conversion protocols. J. Cell. Biochem. 118: 3158–3170, 2017. © 2017 Wiley Periodicals, Inc.
Intramolecular crosstalk between catalytic activities of receptor kinases

ABSTRACT Signal modulation is important for the growth and development of plants and this process is mediated by a number of factors including physiological growth regulators and their associated signal transduction pathways. Protein kinases play a central role in signaling, including those involving pathogen response mechanisms. We previously demonstrated an active guanylate cyclase (GC) catalytic center in the brassinosteroid insensitive receptor (AtBRI1) within an active intracellular kinase domain resulting in dual enzymatic activity. Here we propose a novel type of receptor architecture that is characterized by a functional GC catalytic center nested in the cytosolic kinase domain enabling intramolecular crosstalk. This may be through a cGMP-AtBRI1 complex forming that may induce a negative feedback mechanism leading to desensitisation of the receptor, regulated through the cGMP production pathway. We further argue that the comparatively low but highly localized cGMP generated by the GC in response to a ligand is sufficient to modulate the kinase activity. This type of receptor therefore provides a molecular switch that directly and/or indirectly affects ligand dependent phosphorylation of downstream signaling cascades and suggests that subsequent signal transduction and modulation works in conjunction with the kinase in downstream signaling.
Social Insect-based Sybil Attack Detection in Mobile Ad-hoc Networks

Due to the characteristics of mobile ad-hoc networks (MANETs) such as distributed self-organizing nature and multi-hops communication, bio-inspired approaches proposed to address challenges in these networks. Like in all communication networks, one of the major challenges in MANETs is security provision in these environments. As the traditional approaches such as Public Key Infrastructure (PKI) which are based on central authority are not suitable for dynamic, distributed and cooperative ad-hoc networks, one of the fundamental security threats in MANETs is Identity-based attack. In this work we propose a scheme inspired of the social life of ants, to discriminant the sever Sybil attacker and their related shadow/hidden identities in a self-organized authentication mechanism. For this aim, we adapt the idea of discrimination between mate and non-mate members, in real ants' life, based on aggression concept. We also present our simulation results and discuss some open research issues.
eview he cancer-immunity cycle as rational design for synthetic cancer rugs : Novel DC vaccines and CAR T-cells

Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas. Although encouraging, CAR T-cells have not yet proven clinically effective for solid tumors. This is mainly due to the lack of specific and homogenously expressed targets to direct the T-cells against and a hostile immunosuppressive tumor microenvironment in solid tumors. Cancer
Detection of Polymorphism of Growth Hormone Gene for the Analysis of Relationship between Allele Type and Growth Traits in Karan Fries Cattle

The present study was conducted to detect polymorphism at growth hormone gene in Karan Fries bulls. A 428 bp fragment of growth hormone gene spanning over 4 th exon, 4 th intron and 5 th exon was amplified and digested with AluI restriction enzyme to identify polymorphism at this locus. Karan Fries bulls were found to be polymorphic at this locus. Two genotypes LL and LV were identified in Karan Fries with higher allelic frequency for L allele. In Karan Fries males, the average birth weight, 3 months body weight and daily body weight gains of LL homozygotes were significantly higher than that of LV heterozygotes. Genetic distances of KF bulls with respect to genotype along with 3 months body weight and average daily body weight gain forms a single cluster of bulls with LL genotype, while individuals with LV genotype forms three distinct clusters indicating more influence of L allele on growth traits. (Asian-Aust. J. Anim. Sci. 2004. Vol 17, No. 10 : 1334-1337)
Cryptosporidium, Giardia, Cryptococcus, Pneumocystis Genetic Variability: Cryptic Biological Species or Clonal Near-Clades?

An abundant literature dealing with the population genetics and taxonomy of Giardia duodenalis, Cryptosporidium spp. , Pneumocystis spp. , and Cryptococcus spp. , pathogens of high medical and veterinary relevance, has been produced in recent years. We have analyzed these data in the light of new population genetic concepts dealing with predominant clonal evolution (PCE) recently proposed by us. In spite of the considerable phylogenetic diversity that exists among these pathogens, we have found striking similarities among them. The two main PCE features described by us, namely highly significant linkage disequilibrium and near-clading (stable phylogenetic clustering clouded by occasional recombination), are clearly observed in Cryptococcus and Giardia, and more limited indication of them is also present in Cryptosporidium and Pneumocystis. Moreover, in several cases, these features still obtain when the near-clades that subdivide the species are analyzed separately (“Russian doll pattern”). Lastly, several sets of data undermine the notion that certain microbes form clonal lineages simply owing to a lack of opportunity to outcross due to low transmission rates leading to lack of multiclonal infections (“starving sex hypothesis”). We propose that the divergent taxonomic and population genetic inferences advanced by various authors about these pathogens may not correspond to true evolutionary differences and could be, rather, the reflection of idiosyncratic practices among compartmentalized scientific communities. The PCE model provides an opportunity to revise the taxonomy and applied research dealing with these pathogens and others, such as viruses, bacteria, parasitic protozoa, and fungi.
Analysing the operation of the basic pass transistor structure

Pass transistor logic has become important for the design of low‐power high‐performance digital circuits due to the smaller node capacitances and reduced transistors count it offers. However, the acceptance and application of this logic depends on the availability of supporting automation tools, e.g. timing simulators, that can accurately analyse the performance of large circuits at a speed, significantly faster than that of SPICE based tools. In this paper, a simple and robust modelling technique for the basic pass transistor structure is presented, which offers the possibility of fast timing analysis for circuits that employ pass transistors as controlled switches. The proposed methodology takes advantage of the physical mechanisms in the pass transistor operation. The obtained accuracy compared to SPICE simulation results is sufficient for a wide range of input and circuit parameters. Copyright © 2006 John Wiley & Sons, Ltd.
Broadcasting with Degraded Message Sets : A Deterministic Approach

In this paper we study the nested (degraded) message set problem, where user i ∈ {1, . , K} requires messages W1, . , Wi. We study this for a MIMO linear deterministic broadcast channel model, which is motivated by some recent successes in using such models to obtain insights into approximate characterizations for the Gaussian relay and interference channels. We establish the complete solution for the K = 3 user nested message problem for the MIMO linear deterministic broadcast channel. We also establish some extremal points for the general K-user case, where there are only two messages of interest.
High density nonmagnetic cobalt in thin films

Recently high density (HD) nonmagnetic cobalt has been discovered in a nanoscale cobalt thin film, grown on Si(111) single crystal. This form of cobalt is not only nonmagnetic but also superconducting. These promising results have encouraged further investigations of the growth of the nonmagnetic (NM) phase of cobalt. In the original investigation, the cobalt film had a natural cobalt oxide at the top. We have investigated whether the growth of HD NM cobalt layers in the thin film depends on (i) a capping layer on the cobalt film, (ii) the thickness of the cobalt film and (iii) the nature of the substrate on which the cobalt film is grown. The results of such investigations indicate that for cobalt films capped with a thin gold layer, and for various film thicknesses, HD NM cobalt layers are formed. However, instead of a Si substrate, when the cobalt films are grown on oxide substrates, such as silicon oxide or cobalt oxide, HD NM cobalt layers are not formed. The difference is attributed to the nature—crystalline or amorphous—of the substrate.
Dentin Erosion: Method Validation and Efficacy of Fluoride Protection

The aging population experiences more gingival recession and root exposure which increases the opportunity for dentin erosion. This study tested the use of transverse microradiography (TMR) methods to assess dentin erosion and the interaction between fluoride and citric acid on the amount of erosion in the dentin samples. In a 4 × 3 interaction experimental design, four fluoride concentrations (0.00, 25.0, 50.0, and 100.0 mg/L) and three citric acid concentrations (0.0, 0.25, and 1.00%) were combined to form 12 experimental solutions. Forty-eight dentin samples were placed in the experimental solutions for 1 and 4 h and the amount of surface lost was determined by TMR methods. The resolution of the TMR method was 0.9 μm per pixel with a 0.1% and a 5% confidence interval of ±4.2 μm. Dentin erosion increased with the concentration of citric acid and time, the erosion decreased when concentration of fluoride was increased. Effects due to fluoride and citric acid concentrations individually, and their interaction on the amount of erosion observed was statistically significant (p < 0.0001). This study found that TMR methods are appropriate and that 25.0 mg/L was the optimal fluoride concentration to protect dentin from a 1.00% citric acid challenge.
Design of a decoupled MRI-compatible force sensor using fiber bragg grating sensors for robot-assisted prostate interventions

During prostate needle insertion, the gland rotates and displaces resulting in needle placement inaccuracy. To compensate for this error, we proposed master-slave needle steering under real-time MRI in a previous study. For MRI-compatibility and accurate motion control, the master (and the slave) robot uses piezo actuators. These actuators however, are non-backdrivable. To cope with this issue, force sensor is required. Force sensor is also required at the slave side to reflect the insertion force to clinician’s hand through the master robot. Currently, there is no MRI-compatible force sensor commercially available. In order to generate a combination of linear and rotary motions for needle steering, this study is seeking to develop a MRI-compatible 2 Degrees of Freedom (DOF) force/torque sensor. Fiber Brag Grating (FBG) strain measuring sensors which are proven to be MRI-compatible are used. The active element is made of phosphor-bronze and other parts are made of brass. The force and torque measurements are designed to be entirely decoupled. The sensor measures -20 to 20 N axial force with 0.1 N resolution, and -200 to 200 Nmm axial torque with 1 Nmm resolution. Analytical and Finite Element (FE) analyses are performed to ensure the strains are within the measurable range of the FBG sensors. The sensor is designed to be compact (diameter =15 mm, height =20 mm) and easy to handle and install. The proposed sensor is fabricated and calibrated using a commercial force/torque sensor.
On link availability probability of routing protocols for urban scenario in VANETs

This paper presents the link availability probability. We evaluate and compare the link availability probability for routing protocols; Ad hoc On-demand Distance vector (AODV), Dynamic Source Routing (DSR) and Fisheye State Routing (FSR) for different number of connections and node density. A novel contribution of this work is enhancement in existing parameters of routing protocols; AODV, DSR and FSR as MOD-AODV, MOD-DSR and MOD-FSR. From the results, we observe that MOD-DSR and DSR outperform MOD-AODV, AODV, MOD-OLSR and OLSR in terms of Packet Delivery Ratio (PDR), Average End-to End Delay (AE2ED), link availability probability at the cost of high value of Normalized Routing Overhead (NRO).
Specific Regulation of T Helper Cell 1–mediated Murine Colitis by CEACAM1

Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell surface molecule that has been proposed to negatively regulate T cell function. We have shown that CEACAM1 is associated with specific regulation of T helper cell (Th)1 pathways, T-bet–mediated Th1 cytokine signaling, and Th1-mediated immunopathology in vivo. Mice treated with anti–mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited a reduced severity of trinitrobenzene sulfonic acid colitis in association with decreased interferon (IFN)-γ production. Although oxazolone colitis has been reported as Th2 mediated, mice treated with the CC1 mAb or a CEACAM1-Fc chimeric protein exhibited a reduced severity of colitis in association with a significant reduction of IFN-γ and T-bet activation, whereas signal transducer and activator of antigen 4 activation was unaffected. Both interleukin-4 and IFN-γ gene–deficient mice exhibited less severe colitis induction by oxazolone. Direct ligation of T cells in vitro with the murine hepatitis virus spike protein, a natural ligand for the N-domain of CEACAM1, inhibited the differentiation of naive cells into Th1 but not Th2 cells and activation of Th1 but not Th2 cytokine production. These results indicate that CEACAM1 isoforms are a novel class of activation-induced cell surface molecules on T cells that function in the specific regulation of Th1-mediated inflammation such as that associated with inflammatory bowel disease.
Feature Selection and Model Comparison on Microsoft Learning-to-Rank Data Sets

With the rapid advance of the Internet, search engines (e.g., Google, Bing, Yahoo! ) are used by billions of users for each day. The main function of a search engine is to locate the most relevant webpages corresponding to what the user requests. This report focuses on the core problem of information retrieval: how to learn the relevance between a document (very often webpage) and a query given by user. Our analysis consists of two parts: 1) we use standard statistical methods to select important features among 137 candidates given by information retrieval researchers from Microsoft. We find that not all the features are useful, and give interpretations on the top-selected features; 2) we give baselines on prediction over the real-world dataset MSLR-WEB by using various learning algorithms. We find that models of boosting trees, random forest in general achieve the best performance of prediction. This agrees with the mainstream opinion in information retrieval community that tree-based algorithms outperform the other candidates for this problem.