Miracle-dz/UniFAR-FTUs huggingface dataset:
A PTEN inhibitor displays preclinical activity against hepatocarcinoma cells

ABSTRACT Phosphatase and tensin homolog (PTEN) gene is considered a tumor suppressor gene. However, PTEN mutations rarely occur in hepatocellular carcinoma (HCC), whereas heterozygosity of PTEN, resulting in reduced PTEN expression, has been observed in 32–44% of HCC patients. In the present study, we investigated the effects of the small molecule PTEN inhibitor VO-OHpic in HCC cells. VO-OHpic inhibited cell viability, cell proliferation and colony formation, and induced senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells. VO-OHpic synergistically inhibited cell viability when combined with PI3K/mTOR and RAF/MEK/ERK pathway inhibitors, but only in Hep3B cells, and significantly inhibited tumor growth in nude mice bearing xenografts of Hep3B cells. Therefore, we demonstrated for the first time that VO-OHpic inhibited cell growth and induced senescence in HCC cells with low PTEN expression, and that the combination of VO-OHpic with PI3K/mTOR and RAF/MEK/ERK inhibitors resulted in a more effective tumor cell kill. Our findings, hence, provide proof-of-principle evidence that pharmacological inhibition of PTEN may represent a promising approach for HCC therapy in a subclass of patients with a low PTEN expression.
An XMM-Newton and Chandra Investigation of the Nuclear Accretion in the Sombrero Galaxy (NGC 4594)

We present an analysis of the XMM-Newton and Chandra ACIS-S observations of the LINER nucleus of the Sombrero galaxy, and we discuss possible explanations for its very sub-Eddington luminosity by complementing the X-ray results with high angular resolution observations in other bands. The X-ray investigation shows a hard (Γ = 1.89) and moderately absorbed (NH = 1.8 × 1021 cm-2) nuclear source of 1.5 × 1040 ergs s-1 in the 2-10 keV band, surrounded by hot gas at a temperature of ~0.6 keV. The bolometric nuclear luminosity is at least ~200 times lower than expected if mass accreted on the supermassive black hole, which Hubble Space T elescope shows to reside at the center of this galaxy, at the rate predicted by the spherical and adiabatic Bondi accretion theory and with the high radiative efficiency of a standard accretion disk. The low luminosity, coupled to the observed absence of Fe K emission in the nuclear spectrum, indicates that such a disk is not present. This nucleus also differs from bright unobscured active galactic nuclei in the lack of high flux variability and prominent broad Hα emission. However, it is also too faint for the predictions of simple radiatively inefficient accretion taking place at the Bondi rate; it could instead be too radio bright for radiatively inefficient accretion that includes strong mass outflows or convection. This discrepancy could be solved by the possible presence of nuclear radio jets. An alternative explanation of the low luminosity, in place of radiative inefficiency, could be unsteady accretion.
AUTHSCAN: Automatic Extraction of Web Authentication Protocols from Implementations

Ideally, security protocol implementations should be formally verified before they are deployed. However, this is not true in practice. Numerous high-profile vulnerabilities have been found in web authentication protocol implementations, especially in single-sign on (SSO) protocols implementations recently. Much of the prior work on authentication protocol verification has focused on theoretical foundations and building scalable verification tools for checking manually-crafted specifications [17, 18, 44]. In this paper, we address a complementary problem of automatically extracting specifications from implementations. We propose AUTHSCAN, an end-to-end platform to automatically recover authentication protocol specifications from their implementations. AUTHSCAN finds a total of 7 security vulnerabilities using off-the-shelf verification tools in specifications it recovers, which include SSO protocol implementations and custom web authentication logic of web sites with millions of users.
EWMA control charts for monitoring binary processes with applications to medical diagnosis data

To monitor a binary process, exponentially weighted moving average (EWMA) control charts in different variations are proposed. The average run length performance of the EWMA approach both with standard and with skewness‐corrected 3‐σ control limits is investigated and design recommendations are derived. The proposed EWMA control charts are applied to medical diagnosis data taken from the diagnostic expert system SONOCONSULT in order to provide a semi‐automatic component for monitoring the documentation behavior of different examiners. Copyright © 2010 John Wiley & Sons, Ltd.
On the Viability of Paris Metro Pricing for Communication and Service Networks

Paris Metro Pricing (PMP) is a simple multi-class flat-rate pricing scheme already practiced by transport systems, specifically by the Paris Metro at one time. The name is coined after Andrew Odlyzko proposed it for the Internet as a simple way to provide differentiated services. Subsequently, there were several analytical studies of this promising idea. The central issue of these studies is whether PMP is viable, namely, whether it will produce more profit for the service provider, or whether it will achieve more social welfare. The previous studies considered similar models, but arrived at different conclusions. In this paper, we point out that the key is how the users react to the congestion externality of the underlying system. We derive sufficient conditions of congestion functions that can guarantee the viability of PMP, and provide the relevant physical meanings of these conditions.
Mechanistic links between cellular trade-offs, gene expression, and growth

Significance Cells have finite resources. Committing resources to one task therefore reduces the amount of resources available to others. These trade-offs are often overlooked but potentially modify all cellular processes. Building a mathematical cell model that respects such trade-offs and describes the mechanisms of protein synthesis and how cells extract resources from their environment, we quantitatively recover the typical behavior of an individual growing cell and of a population of cells. As trade-offs are experienced by all cells and because growth largely determines cellular fitness, a predictive understanding of how biochemical processes affect others and affect growth is important for diverse applications, such as the use of microbes for biotechnology, the inhibition of antibiotic resistance, and the growth of cancers. Intracellular processes rarely work in isolation but continually interact with the rest of the cell. In microbes, for example, we now know that gene expression across the whole genome typically changes with growth rate. The mechanisms driving such global regulation, however, are not well understood. Here we consider three trade-offs that, because of limitations in levels of cellular energy, free ribosomes, and proteins, are faced by all living cells and we construct a mechanistic model that comprises these trade-offs. Our model couples gene expression with growth rate and growth rate with a growing population of cells. We show that the model recovers Monod’s law for the growth of microbes and two other empirical relationships connecting growth rate to the mass fraction of ribosomes. Further, we can explain growth-related effects in dosage compensation by paralogs and predict host–circuit interactions in synthetic biology. Simulating competitions between strains, we find that the regulation of metabolic pathways may have evolved not to match expression of enzymes to levels of extracellular substrates in changing environments but rather to balance a trade-off between exploiting one type of nutrient over another. Although coarse-grained, the trade-offs that the model embodies are fundamental, and, as such, our modeling framework has potentially wide application, including in both biotechnology and medicine.
Measuring perceived benefits and perceived barriers for physical activity.

OBJECTIVES To evaluate the psychometric properties and relationship to physical activity levels of the Exercise Benefits/Barriers Scale (EBBS) among college students. METHODS A total of 398 college students completed the EBBS and a measure of self-efficacy, the Physical Exercise Self-Efficacy Scale. In addition, a subsample of 275 students also completed a semistructured interview on physical activity, the Seven-day Physical Activity Recall. RESULTS Psychometric properties were acceptable, but only benefits significantly accounted for variance in physical activity levels. CONCLUSIONS Surprisingly, the factorial structure differed from the test developers'.
The FLUKA code: present applications and future developments

The main features of the FLUKA Monte Carlo code, which can deal with transport and interaction of electromagnetic and hadronic particles, are summarised. The physical models embedded in FLUKA are mentioned, as well as examples of benchmarking against experimental data. A short history of the code is provided and the following examples of applications are discussed in detail: prediction of calorimetric performances, atmospheric neutrino flux calculations, dosimetry in atmosphere and radiobiology applications, including hadrontherapy and space radiation protection. Finally a few lines are dedicated to the FLUKA server, from which the code can be downloaded.
Synthesis and Properties of Al‐Ni‐La Bulk Metallic Glass

More attention has been paid to bulk metallic glasses (BMGs) in recent years due to their superior properties, and they have already been developed successfully in many systems such as Zr-, Fe-, Mg-, Cu-, Ti-, Ni- and La-based alloys. [1–6] In the meantime, Al-based metallic glass has also received particular interest because of its low density and potential aerospace applications. [7] However, an Al-based metallic glassy rod with a diameter of 1 mm has not yet been produced. Mechanical properties of these materials are usually measured by examining wires and ribbons. [8,9] Therefore, the research and application of Al-based metallic glasses are limited to a large extent due to the sample size. It is important and significant to develop Al-based BMGs. Different methods, such as alloying for example, which are popular and effective in other alloy systems, [10] have been employed to improve the glass-forming ability (GFA) of Al-based metallic glasses. They have little effect on the GFA of Al-based alloy systems. [11,12] The low GFA of Al-based alloys results from the existence of local-ordering clusters and high-melting-temperature phases in the alloy melt, which usually act as nucleation sites. This further promotes crystallization: the precipitation of fcc-Al, and intermetallics, which deteriorate the GFA. In this paper, the successful preparation of an Al-based BMG with a diameter of 1 mm in the Al85.5Ni9. 5La5 (in atomic percentage) alloy by a melt-treatment technique is described. The treatment is adapted to not only remove the pre-existing nuclei but also to realize a high cooling rate. The thermal and mechanical properties of the Al85.5Ni9. 5La5 BMG, along with its compressive-fracture behavior are explored for the first time. This work will greatly promote the development and application of Al-based BMGs. Figure 1a shows a photograph of an Al85.5Ni9. 5La5 BMG cylindrical rod with a diameter of 1 mm. The surface is smooth and lustrous, like other as-cast BMGs. Figure 1b shows X-ray diffraction (XRD) patterns of as-cast ribbons, sheets and rods. It can be seen that only one broad diffraction peak in the 2u range from 358 to 458, characteristic of an amorphous structure, is detected, without any crystalline peaks. Figure 2 shows differential scanning calorimetry (DSC) curves of the as-cast ribbons, sheets and rods. The three traces display similar glass-transition and crystallization behaviors and indicate similar amounts of exothermic heat, which is consistent with the XRD results. In comparison to the GFA of Al86Ni9La5 reported in ref. [13], we found that a larger size of amorphous alloy is obtained with our casting strategy than with the ordinary wedge-casting method. COMMUNICATION
Theory and Evidence on the Resolution of Financial Distress

We analyze a financially distressed owner-managed project. The main results of the model are: (1) borrower default is an endogenous response to the anticipated restructuring--foreclosure outcome; (2) the lender's restructuring--foreclosure decision depends critically on the interaction between project value and industry liquidity; and (3) the lender waits for the industry to recapitalize before selling assets obtained through foreclosure. Empirical analysis of a large sample of defaulted commercial real estate loans supports many of the model predictions, including restructuring--foreclosure outcomes that are consistent with endogenous borrower default and firesale discounts that vary depending on industry market conditions at the time of foreclosure. (JEL G33) Copyright 2006, Oxford University Press.
Generation of a mouse mutant by oligonucleotide-mediated gene modification in ES cells

Oligonucleotide-mediated gene targeting is emerging as a powerful tool for the introduction of subtle gene modifications in mouse embryonic stem (ES) cells and the generation of mutant mice. However, its efficacy is strongly suppressed by DNA mismatch repair (MMR). Here we report a simple and rapid procedure for the generation of mouse mutants using transient down regulation of the central MMR protein MSH2 by RNA interference. We demonstrate that under this condition, unmodified single-stranded DNA oligonucleotides can be used to substitute single or several nucleotides. In particular, simultaneous substitution of four adjacent nucleotides was highly efficient, providing the opportunity to substitute virtually any given codon. We have used this method to create a codon substitution (N750F) in the Rb gene of mouse ES cells and show that the oligonucleotide-modified Rb allele can be transmitted through the germ line of mice.
Influence of Combinations of Pesticides and Fertilizers on Aquatic Productivity

We have examined the effects of environmentally realistic concentrations of widely used pesticides and fertilizers for rice paddy in Western Ghats regions of India on chlorophyll and zooplankton production using a laboratory mesocosm. Malathion (100 μg·L-1), Cypermethrin (25 μg·L-1), Nitrate-nitrogen (8 mg·L-1) and Phosphate-phosphorus (8 mg·L-1) in different combinations such as pesticide-pesticide and pesticide-fertilizer were tested in fully factorial manner for a period of 42 days. Study revealed that, chlorophyll production was supported by addition of fertilizers, while combinations of fertilizers with either one or two pesticides reduce the zooplankton density and diversity rendering chlorophyll concentration more than control groups. This could indicate the reason for eutrophication of ponds located in agro-ecosystems. Single application of combinations of pesticides (in spite of presence of fertilizers) even at low concentrations can produce severe negative effects on several taxonomic groups zooplankton living in small shallow water.
Insertional mutagenesis of Listeria monocytogenes with a novel Tn917 derivative that allows direct cloning of DNA flanking transposon insertions

To carry out efficient insertional mutagenesis in Listeria monocytogenes and to facilitate the characterization of disrupted genes, two novel derivatives of Tn917 were constructed, Tn917-LTV1 and Tn917-LTV3. The derivatives (i) transpose at a significantly elevated frequency, (ii) generate transcriptional lacZ fusions when inserted into a chromosomal gene in the appropriate orientation, and (iii) allow the rapid cloning in Escherichia coli of chromosomal DNA flanking transposon insertions. The rapid cloning of DNA flanking insertions is possible because the transposon derivatives carry ColE1 replication functions, a cluster of polylinker cloning sites, and antibiotic resistance genes selectable in E. coli (bla in the case of Tn917-LTV1; neo and ble in the case of Tn917-LTV3). The enhanced transposition frequency of Tn917-LTV1 and Tn917-LTV3 (about 100-fold in Bacillus subtilis) is believed to be due to the fortuitous placement of vector-derived promoters upstream from the Tn917 transposase gene. In L. monocytogenes, Tn917-LTV3 transposed at a frequency of 8 x 10(-4) when introduced on a pE194Ts-derived vector and generated at least eight different auxotrophic mutations. Two nonhemolytic insertion mutants of L. monocytogenes were isolated, and DNA flanking the transposon insertions was cloned directly into E. coli, making use of the ColE1 rep functions and neo gene carried by Tn917-LTV3. Both insertions were shown to be within hlyA, the L. monocytogenes hemolysin structural gene. Although Tn917-LTV1 and Tn917-LTV3 were constructed specifically for genetic analysis of L. monocytogenes, their enhanced transposition frequency and convenience for cloning of DNA adjacent to sites of insertions make them the transposon derivatives of choice for insertional mutagenesis in any gram-positive bacteria that support replication of pE194Ts.
Compatibility-Aware Cloud Service Composition under Fuzzy Preferences of Users

When a single Cloud service (i.e., a software image and a virtual machine), on its own, cannot satisfy all the user requirements, a composition of Cloud services is required. Cloud service composition, which includes several tasks such as discovery, compatibility checking, selection, and deployment, is a complex process and users find it difficult to select the best one among the hundreds, if not thousands, of possible compositions available. Service composition in Cloud raises even new challenges caused by diversity of users with different expertise requiring their applications to be deployed across difference geographical locations with distinct legal constraints. The main difficulty lies in selecting a combination of virtual appliances (software images) and infrastructure services that are compatible and satisfy a user with vague preferences. Therefore, we present a framework and algorithms which simplify Cloud service composition for unskilled users. We develop an ontology-based approach to analyze Cloud service compatibility by applying reasoning on the expert knowledge. In addition, to minimize effort of users in expressing their preferences, we apply combination of evolutionary algorithms and fuzzy logic for composition optimization. This lets users express their needs in linguistics terms which brings a great comfort to them compared to systems that force users to assign exact weights for all preferences.
Analytical Characterization of Shear Localization in Thermoviscoplastic Materials

Abstract : Critical conditions for shear localization in thermoviscoplastic materials are obtained in closed form for idealized models of simple shearing deformations. The idealizations, which include the neglect of heat conduction, inertia, and elasticity, are viewed as quite acceptable for many applications in which shear bands occur. Explicit results obtained for the idealized, but fully nonlinear problem show the roles of strain rate sensitivity, strain hardening, and initial imperfection on the localization behavior. Numerical solutions for two steels are shown to exhibit the principal features reported for torsional Kolsky bar experiments on these steels. Mathematically exact critical conditions obtained for the fully nonlinear problem are compared with critical conditions obtained by means of linear perturbation analysis gives better agreement with the predictions fo the fully nonlinear analysis.
Maximum reward collection problem: a cooperative receding horizon approach for dynamic clustering

In this paper, the Maximum Reward Collection Problem (MRCP) in uncertain environments is investigated where multiple agents cooperate to maximize the total reward collected from a set of moving targets in the mission space with unknown arrival times, trajectories and dynamics. The reward with respect to each of the targets has a time discounting value and can be collected only if a cluster of agents with proper number of elements visits the targets. Meanwhile, in each cluster, it is assumed that agents are able to extract a larger fraction of reward when their configuration in the cluster is close to specific configuration around the respective target. The inherited uncertainty in the environment and the dynamic clustering factor render the one-shot optimization in MRCP rather impractical. Therefore, a Cooperative Receding Horizon (CRH) controller is utilized toward maximizing the collected reward and based on the prediction of the future positions of targets with the given limited information. Some analytical aspects of problem is discussed and the effectiveness and advantages of the proposed algorithm is demonstrated via numerical simulations.
Methodological studies on single meal food intake characteristics in normal weight and obese men and women.

METHOD The eating behaviour of 19 normal weight males, 19 obese males, 19 normal weight females and 19 obese females was measured by means of VIKTOR, our version of the universal eating monitor. The total food intake, the duration of consumption, the rate of consumption, the relative rate of consumption and the subjective motivation to eat were measured during five homogenous lunch meals to analyse how these variables were related to body weight or to sex. Furthermore, the stability of the eating characteristics over the five eating occasions were tested with pre-defined criteria of stability. The predictive validity of the variables measuring subjective motivation to eat and forthcoming food intake was also tested. RESULTS Men ate more food than women; normal weight men by eating for a longer time and obese men by eating faster. Females did not slow down the eating rate towards the end of the meals as much as males did. The obese subjects described themselves as having less motivation to eat prior to meals than normal weight subjects. CONCLUSIONS Total stability, i.e. both relative and absolute stability, for all subjects was present for the eating variables intake of food and eating rate. Of the variables measuring subjective motivation to eat (desire to eat, hunger, fullness and prospective consumption) on visual analogue scales, only the variables desire to eat and prospective consumption predicted forthcoming food intake.
Molecular Pathology in Epidemiologic Studies: A Primer on Key Considerations

The development of molecular pathologic components in epidemiologic studies offers opportunities to relate etiologic factors to specific tumor types, which in turn may allow the development of better overall risk prediction and provide clues about mechanisms that mediate risk factors. In addition, this research may help identify or validate tissue biomarkers related to prognosis and prediction of treatment responses. In this mini review, we highlight specific considerations related to the incorporation of pathology in epidemiologic studies, using breast cancer research as a model. Issues related to ensuring the representativeness of cases for which research tissue is available and understanding limitations resulting from variable procedures for tissue collection, fixation, and processing are discussed. The growing importance of molecular pathology in clinical medicine has led to increased emphasis on optimized tissue preparation, which should enhance this type of research. In addition, the availability of new technologies including tissue microarrays, image scanning, and automated analysis to achieve high-throughput standardized assessment of immunohistochemical markers, and potentially other assays, is enabling consistent scoring of a growing list of markers in large studies. Concurrently, methodologic research to extend the range of assays that can be done on fixed tissues is expanding possibilities for molecular pathologic studies in epidemiologic research. Cancer Epidemiol Biomarkers Prev; 19(4); 966–72. ©2010 AACR.