Miracle-dz/UniFAR-FTUs huggingface dataset:
Blockade of Fatty Acid Synthase Induces Ubiquitination and Degradation of Phosphoinositide-3-Kinase Signaling Proteins in Ovarian Cancer

Aberrations within the phosphoinositide-3-kinase (PI3K) pathway occur in greater than 45% of ovarian carcinomas. The PI3K cascade transmits signals from ErbB receptors downstream to S6 and 4EBP1, which are involved in protein biosynthesis. Many ovarian carcinomas reveal hyperactivation of ErbB1 (epidermal growth factor receptor) or ErbB2 (HER2/neu). Unfortunately, the benefit of anti-ErbB drugs is yet rather limited in ovarian carcinomas. Thus, novel targeting strategies are needed for ovarian carcinomas. The lipogenic enzyme fatty acid synthase (FASN) is overexpressed in approximately 80% of ovarian carcinomas. It stimulates cell growth and signifies poor prognosis. FASN inhibition impedes (ErbB) membrane receptor signaling and sensitizes cells against anti-ErbB drugs. Here, we show that the FASN inhibitor C75 and FASN-targeting siRNAs abrogate growth, induce apoptosis, and downregulate phosphorylation/expression of the PI3K effectors AKT, mTOR, p70S6K, S6, and 4EBP1. In contrast, FASN inhibition impairs expression but only weakly affects phosphorylation of ERK1/2 mitogen-activated protein kinases in ovarian carcinoma cells. Cycloheximide-mediated blockade of protein translation reveals that C75- or FASN siRNA–induced shutdown of FASN accelerates decomposition of signaling proteins. This effect is caused by C75- or FASN siRNA–dependent stimulation of ubiquitination followed by lysosomal-autophagosomal proteolysis. In contrast, PI3K inhibitor LY294002 blocks phosphorylation but does not reduce expression/stability of PI3K effectors. Forced expression of hyperactive (HA) AKT1, unlike HA-MEK1, impairs the growth-inhibitory action of C75. We provide first evidence that the anticancer action of FASN inhibitors is at least partially mediated by drug-dependent proteolysis of PI3K effectors. FASN is a promising cancer target, whose inhibition not only abrogates lipogenesis, which is indispensable for cancer growth, but also downregulates oncogenic PI3K signaling. Mol Cancer Res; 9(12); 1767–79. ©2011 AACR.
The influence of instruction on verbatim and content text recall

This investigation focuses on text recall in eight‐ and nine‐year old children. The main focus was on whether two different sets of instructions had a differential influence: one set instructed students to focus on an orally presented text verbatim, and the other instructed students to focus on its content. A differential influence on verbatim and content recall might indicate separate storage of verbatim and gist information, and could provide evidence for two subprocesses of text processing – that is, for construction and integration. The instructions were administered either before or after hearing the text, and recall was tested again one week later. The results showed differential instruction effects on verbatim and content recall. These effects depended on the time of instruction. Verbatim instruction had an enhancing effect on verbatim recall, both when instructions were given before and when given after text presentation. Content instruction given after text presentation had a suppressing effect on verbatim recall, but involved no advantage for content recall. Content recall was not suppressed by verbatim instruction at any time of instruction. Thus, the processing of content seems to be less situated than the processing of verbatim information.
TOPOGRAPHY OF COTRANSDUCIBLE ARGININE MUTATIONS IN ESCHERICHIA COLI K-12.

HE sequence of enzymatic steps specific for arginine biosynthesis in Escherichia coli is outlined in Figure 1. In mutants of E. coli K-12, the synthesis of any one of the enzymes involved in this pathway, except acetylornithine transaminase (step D) , can be altered by single-step mutation ( GORINI, GUNDER-SEN and BURGER 1961; MAAS 1961; VOGEL 1961). Mutants blocked in step D are known among derivatives of the W strain only (VOGEL, BACON and BAICH 1963). The results of mapping experiments, performed by conjugation techniques with arginine (arg) mutants of E. coli K-12 (for abbreviations see Figure 2), have shown that the loci of the seven known structural genes are distributed among four regions of the bacterial chromosome (Figure 2) (LAVALLE, JACOB and MAAS, see MAAS 1961 j MAAS 1961 ; MAAS and MAAS 1962). Four of them (argB, C, E and H ) lie in the same region, together with two methionine markers and one locus which is most probably the structural gene of a phosphoenolpyruvate carboxylase (VANDERWINKEL, LIARD, RAMOS and WIAME 1963). These markers are cotransducible by the temperate bacteriophage 363 (LAVALLE et al.). An opportunity was thus provided to extend our information about the genetic control of arginine biosynthesis; knowledge of the spatial arrangement of the four arginine loci might throw some light on the mechanism of repression in this pathway. We shall describe the mapping by transduction of the B, C, E and H loci. The significance of the results for studies dealing with control mechanisms in arginine biosynthesis will be briefly discussed. for determinations of the enzyniatic defccts in the argB and C mutants. The strain P4XSB166 (argE) strongly feeds argB and C nutants, since it excretes the utilizablo precursx acrtyl-ornithine: this fact explains the growth on minim21 medium of an argB or C recombinant class in transductions involving as recipient en argE mutint. and as donor. phag, grown on argB or C strains. argH strains do not fax1 othx ai-g mutants; rrrgC strains d3 not fe-d the argB mutant. three-point we csllzction of d3ut)le mutants. In arg-) arg-) appropriate transductions. For from the transduction (recipient glu-2, argH-2) x (donor argB-I). we isolated a (glu-2, argB-l) recombinant; t! iis strain could be distinguished from the other recombinants by its ability to grow on succinate and ornithine (or arginine). (mstf, arg-) strains were transduction of (met-> arg-) organisms to methionine indzpendence with a met+ donor.
Governing the souls of young women: exploring the perspectives of mothers on parenting in the age of sexualisation

The sexualisation of young women has emerged as a growing concern within contemporary western cultures. This has provoked adult anxieties that young women are growing up too fast by adopting inappropriate sexual practices and subjectivities. Psychological discourses have dominated, which position sexualisation as a corrupting force that infects the ‘true self’ of young women, so they develop in abnormal ways. This in turn allows psychological practices to govern how to parent against sexualisation within families. To explore this further, six mothers each with daughters aged between 8 and 12 took part in one to one semi-structured interviews designed to explore how they conceptualised and parented against the early sexualisation of young women. A Foucauldian inspired discourse analysis was employed, which suggested that the mother's talk was situated within a psychological discourse. This enabled sexualisation to be positioned as a corrupting force that disrupted the natural development of young women through deviant bodily practices (e.g. consuming sexualised goods), which prevented them from becoming their ‘true self’. Through the disciplinary gaze of psychology, class inequalities were reproduced where working class families were construed as ‘chavs’ who were bad parents and a site of contagion for sexualisation.
Convergence of a Sparse Representations Algorithm Applicable to Real or Complex Data

Sparse representations has become an important topic in years. It consists in representing, say, a signal (vector) as a linear combination of as few as possible components (vectors) from a redundant basis (of the vector space). This is usually performed, either iteratively (adding a component at a time), or globally (selecting simultaneously all the needed components). We consider a specific algorithm, that we obtain as a fixed point algorithm, but that can also be seen as an iteratively reweighted least-squares algorithm. We analyze it thoroughly and show that it converges to the global optimum. We detail the proof in the real case and indicate how to extend it to the complex case. We illustrate the result with some easily reproducible toy simulations, that further illustrate the potential tracking properties of the proposed algorithm.
Nitric oxide donors induce large‐scale deletion mutations in human lymphoblastoid cells: Implications for mutations in T‐lymphocytes from arthritis patients

Rheumatoid arthritis (RA) is an inflammatory disease in which high levels of reactive nitrogen oxygen species (RNOS) may be present in the affected joints. RNOS are known to produce small‐scale mutational events (transitions, transversions, small insertions, and small deletions) but the ability of these compounds to cause deletion of large segments of genomic DNA has not been previously determined. To address this question, a human lymphoblastoid cell line (WIL2‐NS) was exposed to nitric oxide (NO)–donating drugs and hypoxanthine phosphoribosyltransferase (hprt)–negative clones were selected and analyzed by multiplex‐PCR. Large‐scale deletions accounted for 60–80% of hprt mutations arising in drug‐treated cultures compared to 12% in untreated cultures (P‐values of 0.006 and 0.0001, respectively, in two experiments). Deletion mutations in untreated cultures affected exon 9, whereas 75% of drug‐induced deletion mutations affected exons 2, 3, and 9, and the remainder were very large, ranging from 26 to 1200 kbp. To compare this spectrum of NO‐induced mutations in a lymphoblastoid line to that arising in vivo in arthritis patients, T‐cells from RA patients, osteoarthritis (OA) patients, and controls were cloned and similarly analyzed. We previously showed that the overall frequency of Hprt mutant clones from patients is appreciably elevated compared to that of control subjects. Large‐scale hprt deletions (0.5 to >26 kb) were detected in mutant T‐cell clones from both RA and OA patients and also from control subjects. A total of 54 mutant clones from 16 RA patients and 19 mutant clones from 6 OA patients were studied. Of these, 6 clones (from 3 RA and 1 OA patient) had suffered large‐scale deletions. A total of 9 control subjects were studied and 62 mutant clones were obtained. Of these, 19 had suffered large‐scale deletions, arising in 7 of 9 control subjects. In conclusion, (1) RNOS are capable of inducing large‐scale deletion mutations in a human lymphoblastoid cell line and (2) large‐scale deletion mutations were found in 10–30% of T‐cell clones from RA and OA patients and controls, which we hypothesize may be induced by RNOS. Environ. Mol. Mutagen. 38:261–267, 2001. © 2001 Wiley‐Liss, Inc.
Residential proximity of nearest child and older adults’ receipts of informal support transfers in Barbados

ABSTRACT This study assesses the probability that an older person in Bridgetown, Barbados receives financial, functional and/or material support from their adult children according to the proximity of their nearest child, adjusting for demographic and socio-economic factors. As in many countries of the developing world, older Barbadians receive much of their support from adult children. Population ageing, smaller family sizes and high rates of out-migration may be placing stress on systems of formal and informal support within the country. Yet, very little research has examined determinants of support within the Caribbean let alone Barbados, one of the most rapidly ageing countries in the region. Data (N = 1,248) come from the 2000 Pan American Health Organization Survey on Health, Well-being and Ageing in Latin America and the Caribbean (SABE). Multivariate logistic regression analyses highlight the overwhelming importance of co-residence in the receipt of informal support transfers. Although there is a lower probability of receiving support as distance to nearest child increases, several indicators of vulnerability, such as having a disability, increases support probabilities among those whose nearest children live outside the neighbourhood. The results have implications for current and future cohorts of older adults in the region given the combination of declining fertility, persistent migration and population ageing within a broader context of social protection systems across the region.
What Is a Good Job? A New Measure of Labor-Market Success

No currently available index allows investigators to estimate the overall desirabitlity of specific jobs. With data collected in the 1980 Survey of Job Charactersitics, an index of job desirability (IJD) can be constructed to fill this gap. The IJD incorporates 13 nonmonetary job characteristics along with measures of earnings and weights all job characteristics according to their effects on workers' judgments about how "good" their current jobs are compared with an average job. While earnings are the most important single determinant of a job's desirability, the 13 nonmonetary job characteristics together are twice as important as earnings. Unlike occupational status and earnings, the proposed index explains almost the entire effect of race, sex, educational attainment, and experience on job ratings. It also explains almost all the variation in job ratings provided by workers in different occupations. Furthermore, taking account of nonmonetary job characteristics more than doubles the estimated level of labor-market inequality. White skin, male gender, favorable social origins, high educational attainment, and extensive labor-market experience are also worth two to five times.
Mutation-Based Fault Localization for Real-World Multilingual Programs (T)

Programmers maintain and evolve their software in a variety of programming languages to take advantage of various control/data abstractions and legacy libraries. The programming language ecosystem has diversified over the last few decades, and non-trivial programs are likely to be written in more than a single language. Unfortunately, language interfaces such as Java Native Interface and Python/C are difficult to use correctly and the scope of fault localization goes beyond language boundaries, which makes debugging multilingual bugs challenging. To overcome the aforementioned limitations, we propose a mutation-based fault localization technique for real-world multilingual programs. To improve the accuracy of locating multilingual bugs, we have developed and applied new mutation operators as well as conventional mutation operators. The results of the empirical evaluation for six non-trivial real-world multilingual bugs are promising in that the proposed technique identifies the buggy statements as the most suspicious statements for all six bugs.
Algebraic Decoding of Cyclic Codes Without Error-Locator Polynomials

The algebraic decoding of a p-ary cyclic code consists of four steps: 1) computation of the known syndromes using the received word; 2) computation of the unknown syndromes from the known syndromes; 3) computation of the error positions by a use of the Berlekamp-Massey (BM) algorithm and Chien's search; and 4) computation of the error values by solving a linear system. This paper addresses two problems of determining the error positions and computing the unknown syndromes. To solve the first problem, a new matrix, together with Gaussian elimination instead of the BM algorithm and Chien's search, is proposed. In this new simplified decoder, finding an error-locator polynomial is completely avoided. A main advantage of the presented decoding method is when the Bose-Chaudhuri-Hocquenghem bound is unequal to the minimum distance of the code. Some cyclic codes, which do not have 2t consecutive known syndromes, can be decoded up to their actual minimum distance by using the presented matrix once. To solve the second problem, two algorithms for different square matrices reported recently by Lee et al. are also provided to calculate the value of an unknown syndrome. Finally, an algebraic decoding of the (47,23,15) ternary cyclic code is given.
Writing and the development of the self- heuristic inquiry: A unique way of exploring the power of the written word

This article presents a heuristic research project designed to explore the role of personal writing in the development of the self. True to the heuristic process as outlined by Moustakas, the author analyzed over 30 years of personal poetry and journal writing through her mother's mental illness and brother's traumatic brain injury and epilepsy. Phase two of the project included nine participants (co-researchers) who were lifetime writers. Results indicated themes related to the (i) interpersonal and personal nature of writing, (ii) the spiritually transcendent nature of writing, (iii) the fact that writing facilitates perspective taking, (iv) the importance of challenge in personal growth, (v) the dynamic nature of writing, and (vi) the power of writing to influence personal identity. The paper presents the process, stories of the author and three participants, synthesized results, the power of the heuristic process, and potential application to the creative arts.
College students' stereotypes of gender and political activism

Previous research has investigated gender stereotypes and attitudes toward feminists. Little attention has been paid, however, to assessing public sentiment toward supporters of the emerging Men's Movement. In this study, 120 male and female undergraduates were presented with a description of a political activist. The experimental design consisted of varying the gender (i.e., male vs. female) and political orientation (i.e., advocacy of individualistic rights vs. profeminist advocacy of gender equality) of the target person. Subjects evaluated the stimulus description using a set of semantic differential trait rating scales and a series of life outcome measures. Results suggested that female activists, regardless of political orientation, were perceived as being. more extraverted and were judged to be more likely to meet individual career goals than their male counterparts. In contrast, male activists were judged to be more successful in attaining family goals than female activists. Analyses of variance revealed polarized evaluations of male and female feminist activists. Male feminists were rated higher on interpersonal warmth than female feminists, and female feminists were seen as being the least likely to achieve their family goals. Implications for female and male gender-role activists are discussed
Ghrelin and Insulin Secretion in Humans: Not a Tale of Two Hormones?

Failure of pancreatic β-cells to secrete adequate amounts of insulin is a fundamental defect in type 1 and type 2 diabetes, and the search for innovative strategies to improve β-cell mass and function is a major priority in diabetes research. Ghrelin, a 28-amino acid peptide hormone predominantly secreted by the stomach, was identified as ligand of the growth hormone secretagogue receptor type-1a (GHSR-1a) (1). The Ser3-octanoylated ghrelin form (acylated ghrelin [AG]) also was soon recognized to act as a hypothalamic orexigenic signal (2) and to modulate tissue pathways and functions as a potential contributor to metabolic adaptation to low nutrient availability. Experimental AG administration commonly causes weight gain and hyperglycemia by enhancing food intake, fat deposition, and hepatic gluconeogenesis (3–5). A more comprehensive understanding of the metabolic impact of ghrelin has been recently allowed by the increasing appreciation of the independent, and generally more favorable, effects of its unacylated form (UAG), which does not increase food intake or circulating glucose in vivo (3,4,6). Although no specific UAG receptor has been yet identified, UAG coadministration may counteract the glucogenic effects of AG as well as AG-induced hyperglycemia (3,4,7), and positive or negative associations have been respectively reported in humans between AG or UAG and markers of whole-body insulin resistance (8). Modulating the AG–UAG balance by inhibiting the acylating enzyme ghrelin O-acyltransferase (9) or by …
Organizational violence and aggression: Development of the three-factor Violence Climate Survey

Abstract Violence climate, a concept derived from the safety climate literature, may affect violence and aggression at work. This paper builds upon the unidimensional instrument tested by Spector, Coulter, Stockwell, and Matz (2007). The present instrument, the Violence Climate Survey is a new three-dimensional construct of violence climate consisting of Policies and Procedures, Practices, and Pressure for Unsafe Practices. Using a heterogeneous sample of 216 employees from a variety of organizations in the USA, it was shown that violence climate is significantly related to exposure to physical violence and verbal aggression, physical strains, and psychological strains including job dissatisfaction and negative emotion at work. Exposure to both violence and aggression was associated with all strains. Multiple regression analyses suggested that it was primarily Policies and Pressure that was associated with verbal aggression, whereas mainly Practices was related to physical violence. It is suggested that the construct of violence climate may be a useful subject for further research. In practice, policies may be useful in reducing verbal aggression, but physical violence requires more direct management action and practice.
Anti–Melanoma Differentiation–Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti–melanoma differentiation–associated gene 5 (anti–MDA‐5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti–MDA‐5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM.
The Impact of the Internet on Cancer Outcomes

Each day, more than 12.5 million health‐related computer searches are conducted on the World Wide Web. Based on a meta‐analysis of 24 published surveys, the author estimates that in the developed world, about 39% of persons with cancer are using the Internet, and approximately 2.3 million persons living with cancer worldwide are online. In addition, 15% to 20% of persons with cancer use the Internet “indirectly” through family and friends. Based on a comprehensive review of the literature, the available evidence on how persons with cancer are using the Internet and the effect of Internet use on persons with cancer is summarized. The author distinguishes four areas of Internet use: communication (electronic mail), community (virtual support groups), content (health information on the World Wide Web), and e‐commerce. A conceptual framework summarizing the factors involved in a possible link between Internet use and cancer outcomes is presented, and future areas for research are highlighted.