Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy limits the cytotoxic effects of the AKT inhibitor AZ7328 in human bladder cancer cells

Background: Mutations that activate the PI3K/AKT/mTOR pathway are relatively common in urothelial (bladder) cancers, but how these pathway mutations affect AKT dependency is not known. We characterized the relationship between AKT pathway mutational status and sensitivity to the effects of the selective AKT kinase inhibitor AZ7328 using a panel of 12 well-characterized human bladder cancer cell lines. Methods: Sequenome DNA sequencing was performed to identify mutations in a panel of 12 urothelial cancer cell lines. Drug-induced proliferative inhibition and apoptosis were quantified using MTT assays and propidium iodide staining with FACS analyses. Protein activation via phosphorylation was measured by immunoblotting. Autophagy was measured by LC3 immunofluorescence and immunoblotting. Results: AZ7328 inhibited proliferation and AKT substrate phosphorylation in a concentration-dependent manner but had minimal effects on apoptosis. Proliferative inhibition correlated loosely with the presence of activating PIK3CA mutations and was strengthened in combination with the mTOR inhibitor rapamycin. AZ7328 induced autophagy in some of the lines, and in the cells exposed to a combination of AZ7328 and chemical autophagy inhibitors apoptosis was induced. Conclusions: The cytostatic effects of AZ7328 correlate with PIK3CA mutations and are greatly enhanced by dual pathway inhibition using an mTOR inhibitor. Furthermore, AZ7328 can interact with autophagy inhibitors to induce apoptosis in some cell lines. Overall, our results support the further evaluation of combinations of PI3K/AKT/mTOR pathway and autophagy inhibitors in pre-clinical in vivo models and ultimately in patients with PIK3CA mutant bladder cancers.
Controlling TCP Fairness in WLAN access networks

In this paper, we study the problem of maintaining fairness for TCP connections in wireless local area networks (WLANs) based upon the IEEE 802.11 standard. Current implementations of 802.11 use the so-called Distributed Coordination Function (DCF) which provides similar medium access priority to all stations. Although this mode of operation ensures fair access to the medium at the MAC level, it does not provide any provisions for ensuring fairness among the TCP connections. TCP unfairness may result in significant degradation of performance leading to users perceiving unsatisfactory quality of service. We propose and analyze two solutions that are capable of enabling TCP fairness with minimal additional complexity. The proposed solutions are based on utilizing a rate-control mechanism in two modes: static or adaptive. They do not require modifying existing standards at the MAC or network layers. Hence, they are fully compatible with existing devices. Our performance analysis results prove the efficaciousness of our proposed solutions in achieving TCP fairness compared to existing approaches.
Osmium isotope and highly siderophile element geochemistry of mantle xenoliths from NW Turkey: implications for melt depletion and metasomatic history of the sub-continental lithospheric mantle

Ultramafic xenoliths entrained in the late Miocene alkali basalts and basanites from NW Turkey include refractory spinel-harzburgites and dunites accompanied by subordinate spinel-lherzolites. Whole-rock major and trace element characteristics indicate that the xenoliths are mostly the solid residues of varying degrees of partial melting (∼4–∼15%), but some have geochemical signatures reflecting the processes of melt/rock interaction. Mantle-normalized trace element patterns for the peridotites vary from LREE-depleted to strongly LREE-enriched, reflecting multistage mantle processes from simple melt extraction to metasomatic enrichment. Rhenium and platinum group element (PGE) abundances and 187Os/188Os systematics of peridotites were examined in order to identify the nature of the mantle source and the processes effective during variable stages of melt extraction within the sub-continental lithospheric mantle (SCLM). The peridotites are characterized by chondritic Os/Ir and Pt/Ir ratios and slightly supra-chondritic Pd/Ir and Rh/Ir ratios, representing a mantle region similar in composition to the primitive mantle (PM). Moderate enrichment in PPGE (Pd–Pt–Rh)/IPGE (Ir–Os–Ru) ratios with respect to the PM composition in the metasomatized samples, however, reflects compositional modification by sulphide addition during possible post-melting processes. The 187Os/188Os ratios of the peridotites range from 0.11801 to 0.12657. Highly unradiogenic Os isotope compositions (γOs at 10 Ma from –7.0 to –3.2) in the chemically undisturbed mantle residues are accompanied by depletion in Re/Os ratios, suggesting long-term differentiation of SCLM by continuous melt extraction. For the metasomatized peridotites, however, systematic enrichments in PPGE and Re abundances, and the observed positive covariance between 187Re/188Os and γOs can most likely be explained by interaction of solid residues with basaltic melts produced by melting of relatively more radiogenic components in the mantle. Significantly, the wide range of 187Os/188Os ratios characterizing the entire xenolith suite seems to be consistent with multistage evolution of SCLM and suggests that parts of the lithospheric mantle contain materials that have experienced ancient melt removal (∼1.3 Ga) which created time-integrated depletion in Re/Os ratios; in contrast, some other parts display evidence indicative of recent perturbation in the Re–Os system by sulphide addition during interaction with metasomatizing melts.
A data-mining approach to biomarker identification from protein profiles using discrete stationary wavelet transform

ObjectiveTo develop a new bioinformatic tool based on a data-mining approach for extraction of the most informative proteins that could be used to find the potential biomarkers for the detection of cancer.MethodsTwo independent datasets from serum samples of 253 ovarian cancer and 167 breast cancer patients were used. The samples were examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The datasets were used to extract the informative proteins using a data-mining method in the discrete stationary wavelet transform domain. As a dimensionality reduction procedure, the hard thresholding method was applied to reduce the number of wavelet coefficients. Also, a distance measure was used to select the most discriminative coefficients. To find the potential biomarkers using the selected wavelet coefficients, we applied the inverse discrete stationary wavelet transform combined with a two-sided t-test.ResultsFrom the ovarian cancer dataset, a set of five proteins were detected as potential biomarkers that could be used to identify the cancer patients from the healthy cases with accuracy, sensitivity, and specificity of 100%. Also, from the breast cancer dataset, a set of eight proteins were found as the potential biomarkers that could separate the healthy cases from the cancer patients with accuracy of 98.26%, sensitivity of 100%, and specificity of 95.6%. ConclusionThe results have shown that the new bioinformatic tool can be used in combination with the high-throughput proteomic data such as SELDI-TOF MS to find the potential biomarkers with high discriminative power.
Fast Convergence Rates for Excess Regularized Risk with Application to SVM

where F (w) = Eθ [f(w; θ)] (2) is the expectation of a random function f(·; θ), and the optimization is based on a sample f(·; θ1), . , f(·; θn) of i.i. d. instantiations of f(·; θ). Instead of thinking of a “random function”, one can think of a fixed and known function f(w; θ), and a distribution over the parameter θ. A special case is the familiar prediction setting where θ = (x, y) is an instance-label pair and, e.g., f(w; x, y) = `(〈w,x〉, y) for some loss function `. However, we would like to emphasize that we do not assume any metric or other structure on the parameter θ. In this paper, we are given a random sample of functions (i.e. parameters θ) and can find the empirical minimizer
New change detection tracking method based on background model

Background constructing and updating are the two key problems for the background subtraction method used to the detection of the moving target. In the paper, confident exponent is proposed to construct the original background, and an adaptive strategy is applied to update the background in time. This method was applied on tracking the car in the exam of driver's license. The experiments showed that this method was very promising and could overcome the background change and target change.
SVR-PAIRWISE method to predict MHC-II binding peptides

Peptides binding to MHC molecules is of great importance in the process of triggering and initiating immune responses. There are two main kinds of MHC molecules, MHC class I and class II, and the prediction of MHC-II binding peptides is much more difficult due to their variable lengths, which makes it difficult to construct a preferable prediction model by using most of the existing methods. This paper presents a method, called as SVR-PAIRWISE, to combine Support Vector Regression (SVR) and pairwise alignment, to quantitatively predict the MHC-II binding peptides. The comparison results with some popular methods show its satisfying performances.
Insulin-Like Growth Factor-1 and Bone Morphogenetic Protein-2 Jointly Mediate Prostaglandin E2-Induced Adipogenic Differentiation of Rat Tendon Stem Cells

Tendinopathy is characterized histopathologically by lipid accumulation and tissue calcification. Adipogenic and osteogenic differentiation of tendon stem cells (TSCs) are believed to play key roles in these processes. The major inflammatory mediator prostaglandin E2 (PGE2) has been shown to induce osteogenic differentiation of TSCs via bone morphogenetic protein-2 (BMP-2), and BMP-2 has also been implicated in adipogenic differentiation of stem cells. We therefore examined the mechanisms responsible for PGE2-induced adipogenesis in rat TSCs in vitro. Insulin-like growth factor-1 (IGF-1) mRNA and protein were significantly up-regulated in PGE2-stimulated TSCs, measured by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Incubation with specific inhibitors of cAMP, cAMP-dependent protein kinase A (PKA), and CCAAT/enhancer binding protein-δ (CEBPδ) demonstrated that IGF-1 up-regulation occurred via a cAMP/PKA/CEBPδ pathway. Furthermore, neither IGF-1 nor BMP-2 alone was able to mediate adipogenic differentiation of TSCs, but IGF-1 together with BMP-2 significantly increased adipogenesis, indicated by Oil Red O staining. Moreover, knock-down of endogenous IGF-1 and BMP2 abolished PGE2-induced adipogenic differentiation. Phosphorylation of CREB and Smad by IGF-1 and BMP-2, respectively, were required for induction of the adipogenesis-related peroxisome proliferator-activated receptor γ2 (PPARγ2) gene and for adipogenic differentiation. In conclusion, IGF-1 and BMP-2 together mediate PGE2-induced adipogenic differentiation of TSCs in vitro via a CREB- and Smad-dependent mechanism. This improved understanding of the mechanisms responsible for tendinopathies may help the development of more effective therapies.
Origin and thermal evolution of Mars.

The thermal evolution of Mars is governed by subsolidus mantle convection beneath a thick lithosphere. Models of the interior evolution are developed by parameterizing mantle convective heat transport in terms of mantle viscosity, the superadiabatic temperature rise across the mantle, and mantle heat production. Geological, geophysical, and geochemical observations of the compositon and structure of the interior and of the timing of major events in Martian evolution are used to constrain the model computations. Such evolutionary events include global differentiation, atmospheric outgassing, and the formation of the hemispherical dichotomy and Tharsis. Numerical calculations of fully three-dimensional, spherical convection in a shell the size of the Martian mantle are performed to explore plausible patterns of Martian mantel convection and to relate convective features, such as plumes, to surface features, such as Tharsis. The results from the model calculations are presented.
A system for LEASE: location estimation assisted by stationary emitters for indoor RF wireless networks

We present LEASE, a new system and framework for location estimation assisted by stationary emitters for indoor RF wireless networks. Unlike previous studies, we emphasize the deployment aspect of location estimation engines. Motivated thus, we present an adaptable infrastructure-based system that uses a small number of stationary emitters (SEs) and sniffers employed in a novel way to locate standard wireless clients in an enterprise. We present the components of the system and its architecture, and new non-parametric techniques for location estimation that work with a small number of SEs. Our techniques for location estimation can also be used in a client-based deployment. We present experimental results of using our techniques at two sites demonstrating the ability to perform location estimation with good accuracy in our new adaptable framework.
Enhancing instream flow benefits in an era of water marketing

Growing populations in the western United States demand water not only for residential use and to support urban development but also for recreation, water quality enhancement, improvement of fish and wildlife habitat and to preserve the aesthetics of riparian areas. Instream flows contribute substantial economic benefits, and emerging pressure to reserve water instream comes at a time when markets are evolving to reallocate water among offstream uses such as agriculture, industry and municipal expansion. This article examines current instream flow policies in the western states and outlines the economic values generated by stream flows. The author argues that instream values are high enough to compete in the market for water rights with offstream uses when important recreation sites and wildlife species are involved. The paper suggests how western state policies might be altered to accommodate instream flow protection within the context of water marketing, with the objective of improving the efficiency of water allocation among instream and consumptive uses.
Math learning materials combining print materials and web based training

This paper presents a new type of math learning materials which combines print materials and web materials. By reading a two-dimensional bar code on the print material with a mobile phone camera, students are able to access the web materials easily. The print materials are used to avert the problems of inputting equations into computer and to promote the writing of equation in the process of answering. The web materials are used to ensure the efficient learning through the reference to the linked pages one after another.
Additional file 4: Figure S3. of Selective proliferative response of microglia to alternative polarization signals

Cellular localization of Ki67 immunostaining in brain astrocytes. Brain sections were analyzed by immunohistochemistry for the expression of Ki67 using antibodies against Ki67 (green labeling) and GFAP (red staining) following the icv administration of 250Â ng IL-4. Ki67-positive cells co-localize with GFAP-positive cells (white arrows). Scale bar, 10Â Iźm. (PDF 105 kb)
Popularity Meter: An Influence- and Aesthetics-aware Social Media Popularity Predictor

Social media websites have become an important channel for content sharing and communication between users on social networks. The shared images on the websites, even the ones from the same user, tend to receive a quite diverse distribution of views. This raises the problem of image popularity prediction on social media. To address this important research topic, we explore three essential components that have considerable impact of the image popularity, which are user profile, post metadata, and photo aesthetics. Moreover, we make use of state-of-the-art predictive modeling approaches to demonstrate the effectiveness of our proposed features in predicting image popularity. We then evaluate the proposed method through a large number of real image posts from Flickr. The experimental results show significant statistical evidence that incorporating the proposed features with ensemble learning method that combines predictions from support vector regression (SVR) and classification and regression tree (CART) models offers a satisfactory popularity prediction. By understanding the social behavior and the underlying structure of content popularity, our research results can also contribute to designing better algorithms for important applications like content recommendation and advertisement placement.
Polyphenols as dietary supplements: A double-edged sword

Increased consumption of fruits and vegetables is associated with a lower risk of chronic disease such as cardiovascular disease, some forms of cancer, and neurodegeneration. Pro-oxidant-induced oxidative stress contributes to the pathogenesis of numerous chronic diseases and, as such, dietary antioxidants can quench and/or retard such processes. Dietary polyphenols, ie, phenolic acids and flavonoids, are a primary source of antioxidants for humans and are derived from plants including fruits, vegetables, spices, and herbs. Based on compelling evidence regarding the health effects of polyphenol-rich foods, new dietary supplements and polyphenol-rich foods are being developed for public use. Consumption of such products can increase dietary polyphenol intake and subsequently plasma concentrations beyond expected levels associated with dietary consumption and potentially confer additional health benefits. Furthermore, bioavailability can be modified to further increase absorption and ultimately plasma concentrations of polyphenols. However, the upper limit for plasma concentrations of polyphenols before the elaboration of adverse effects is unknown for many polyphenols. Moreover, a considerable amount of evidence is accumulating which supports the hypothesis that high-dose polyphenols can mechanistically cause adverse effects through pro-oxidative action. Thus, polyphenol-rich dietary supplements can potentially confer additional benefits but high-doses may elicit toxicity thereby establishing a double-edge sword in supplement use.
The Tetanus Neurotoxin‐Sensitive and Insensitive Routes to and from the Plasma Membrane: Fast and Slow Pathways?

Intracellular membrane trafficking in eukaryotes involves the budding of vesicles from a donor compartment, their translocation, and subsequent fusion with a target membrane. This last step has been shown to involve SNARE proteins, classified into two categories, vesicular (v)‐SNAREs and target (t)‐SNAREs. It is the pairing of v‐ and t‐SNAREs that is responsible for bringing the lipid bilayers together for membrane fusion. Key to the discovery of SNAREs is the sensitivity of their neuronal synaptic prototypes, which mediate the release of neurotransmitters, to clostridial neurotoxins. In this review, we focus on tetanus neurotoxin‐sensitive and tetanus neurotoxin‐insensitive v‐SNAREs, in particular synaptobrevin and cellubrevin, both tetanus neurotoxin‐sensitive and Tetanus neurotoxin‐ Insensitive Vesicle‐Associated Membrane Protein (TI‐VAMP, also called VAMP7). The brevins are characterized by an RD sequence in the middle of their SNARE motif whereas TI‐VAMP has an RG sequence. These two categories of exocytic v‐SNAREs define two important routes to and from the plasma membrane: one sensitive, the other insensitive to tetanus neurotoxin. We also discuss the central role of the endosomal system that could be considered, as already suggested for Rab proteins, as a mosaic of v‐SNAREs, thus raising the question of whether or not these two routes can merge, and if so, how and where.
Urea and creatinine concentration, the urea:creatinine ratio

The main focus of the first article [1] was physiological topics, such as urea production and renal processing of urea. The causes of increased and reduced plasma/ serum urea concentration were also discussed. The main focus of this second article is the clinical value of simultaneous measurement of urea and creatinine and calculation of the urea: creatinine ratio. The causes of increased and decreased ratio will be outlined and clinical application of the ratio will be discussed. The article begins with a short discussion of the comparative merits of urea and creatinine measurement for assessment of renal function; this discussion is helpful for an understanding of the potential clinical value of calculating the ratio.
Neutralization Assay for Human Group C Rotaviruses Using a Reverse Passive Hemagglutination Test for Endpoint Determination

ABSTRACT A novel neutralization assay for human group C rotavirus (CHRV) was developed by using a reverse passive hemagglutination (RPHA) test for endpoint determination. In this assay, the neutralization (N)-RPHA test, serial twofold dilutions of sera were mixed with a solution of CHRV that yielded an RPHA test titer of 8 at 3 days after infection. The mixtures were incubated at 37°C for 1 h and were inoculated onto CaCo-2 cell monolayers in a 96-well microplate. Maintenance medium containing 100 μg of pancreatin per ml was placed in each well. The plate was sealed with sticky plastic film and was incubated at 37°C for 3 days under continuous rotation. Then, the RPHA test titer of each well was determined. The neutralization titer was expressed as the reciprocal of the maximum dilution of the serum that exhibited a fourfold (75%) or greater reduction in the RPHA test titer (8 to 2 or less). Seroconversion of neutralizing antibody was demonstrated by this method in four sets of paired serum specimens from patients with diarrheal disease caused by CHRV. The seroprevalence of CHRV in the general population in Okayama Prefecture was 26.8% by immunofluorescence and 25.5% by the N-RPHA test. The N-RPHA test described here is the first system used to assay for a neutralization antibody against CHRV and is applicable in both clinical and epidemiological settings.
Neurones in cat parastriate cortex sensitive to the direction of motion in three‐dimensional space

1. On psychophysical grounds, Beverley & Regan suggested that in man different neural mechanisms mediate the binocular perception of movement in depth and the binocular perception of positional (static) depth. They proposed that the human visual pathway contains several neural mechanisms, each sensitive to a different direction of motion in space. These mechanisms compute the direction of motion from the relative speeds and directions of movement of the left and right retinal images.
Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition

Recently, two novel concepts have emerged in cancer biology: the role of so-called “cancer stem cells” in tumor initiation, and the involvement of an epithelial-mesenchymal transition (EMT) in the metastatic dissemination of epithelial cancer cells. Using a mammary tumor progression model, we show that cells possessing both stem and tumorigenic characteristics of “cancer stem cells” can be derived from human mammary epithelial cells following the activation of the Ras-MAPK pathway. The acquisition of these stem and tumorigenic characters is driven by EMT induction.