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Love is the most worn-out and debased word that humanity often utters. In modern times it is understood in the Freudian views as an instinct-dominated outlook whose function is instinctual gratification that is narcissistic and infantile. On the other hand, this type of love relation also reflects a utilitarian motive of using the \"other\" merely as a tool or means to an end and motivated by the maxim of quantifiable happiness or pleasure. This seemingly ?love for - the - other? dominates the passionate aspect characterized by mere pleasure or genital sexual primacy, a ?need-satisfying object?. In contrast, the true essence of love is grounded on responsibility ?for - the - other? as the good in itself as proposed by Emmanuel Levinas. The absorption of humanity towards this ?disintegrated love? lurks a certain danger, a danger as such. This paper argues that (1) ?love without lust? is possible as depicted in Levinas' discourse on ?Being - for - the - Other? and (2) this concept of ?love without lust? grounded on the ?otherness of the other? is possible through the act of motherhood (Rakhamim).

Although intratumor heterogeneity has been inferred in multiple myeloma (MM), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with MM, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 ( IRF4 ) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγ null xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.

The mechanisms involved in the progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia (PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole-genome sequencing on a series of MGUS ( n =4), high-risk (HR)SMM ( n =4), MM ( n =26) and PCL ( n =2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors that drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease, the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage.

This study aims to contribute to advancing the understanding of entrepreneurial ecosystems, Latin American development, and the evolution and future perspectives of the Middle East. It used a cross-sectional research design and quantitative data with 750 observations from the Global Entrepreneurship Monitor, specifically the National Experts Survey and the Adult Population Survey. The results were analyzed by the Partial Least Squares Technique (PLS-SEM) by grouping countries into two balanced samples of underexplored regions: the Middle East and Latin America. The two regions, Latin America and the Middle East, have diverse entrepreneurial ecosystems; each condition impacts entrepreneurial activities in different ways. In Latin America, the most significant variable is “Physical Infrastructure”, while in the Middle East, the most significant determinants are “Commercial and Professional Infrastructure” and “Entrepreneurship Culture”. This study shows that to support entrepreneurial activities, each region requires different settings for their entrepreneurial ecosystems. It contributes to the literature on regional entrepreneurial ecosystems and to less explored regions to advance our understanding, which will drive better policies and actions.

Understanding the impact of entrepreneurship education on the entrepreneurial cognition of university students is relevant to finding ways to foster entrepreneurship that boost the economy in developing countries. The objective of this study is to determine the influence of personal attitude, perceived behavioral control, and subjective norms on entrepreneurial intention, and to discover if there exists a moderation effect of entrepreneurship education on the abovementioned aspects. We collected 343 questionnaires of students of the Center for Administrative and Economic Sciences of a Mexican university. We used structural equations through the method of partial minimum squares, and, to test the hypothesis, we used the Smart-PLS 3.0 software. The results indicate that entrepreneurship education does not have a significant moderation effect on the relationship between personal attitude on entrepreneurial intention and perceived behavioral control on entrepreneurial intention. However, there exists a significant and positive influence of personal attitude on entrepreneurial intention and perceived behavioral control on entrepreneurial intention. We conclude that current entrepreneurship education has the opportunity to create impactful outcomes because the theory is easy, but entrepreneurship in reality is hard and requires more effort. We recommend including a wider view with external resources like lectures of experts from the entrepreneurial ecosystem and support from government and potential investors, among other approaches.

Five breast cancer subtypes have been described in s poradic b reast c ancer (SBC) using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B. These molecular subtypes show different g enomic a berration p atterns (GAPs). Recently, our group described these breast cancer subtypes in 50 non- BRCA1/2 familial tumors using immunohistochemistry assays. We extended this study to the other classes of f amilial b reast c ancer (FBC), including 62 tumors (18 BRCA1 , 16 BRCA2 and 28 non- BRCA1/2 ), with the same panel of 25 i mmuno h isto c hemical (IHC) markers and histological grade obtaining a similar classification. We combined these data with results generated by a 1 Mb BAC array-based CGH study to evaluate the genomic aberrations of each group. We found that BRCA1- related tumors are preferentially basal-like, whereas non- BRCA1/2 familial tumors are mainly luminal A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors had a greater number of gains/losses, while luminal B tumors had more high-level DNA amplifications. Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC.

The two-parameter Weibull distribution is the predominant distribution in reliability and lifetime data analysis. The classical approach for estimating the scale ( α ) and shape ( β ) parameters employs the maximum likelihood estimation (MLE) method. However, most MLE based-methods resort to numerical or graphical techniques due to the lack of closed-form expressions for the Weibull β parameter. A Weibull β parameter estimator based on perturbation theory is proposed in this work. An explicit expression for β is obtained, making the estimation of both parameters straightforward. Several right-censored lifetime data sets with different sample sizes and censoring percentages were analyzed in order to assess the performance of the proposed estimator. Study case results show that our parameter estimator provides solutions of high accuracy, overpassing limitations of other parameter estimators.

Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of developing breast and other cancers; however, remarkable differences exist regarding disease manifestation in mutation carriers. It has been suggested that other genetic and/or environmental factors modify not only the appearance but also the age of onset and type of tumor in BRCA1/2‐associated cases. The aim of the present study was to investigate the role of two p53 polymorphisms (c.97‐147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we investigated the possible association between the two polymorphisms and disease status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or ovarian cancer families. Genotype and haplotype analyses revealed that the presence of a specific haplotype carrying the allele without the 16‐bp insertion and the variant allele for the Arg72Pro (No Ins‐72Pro haplotype) was associated with an earlier age of onset in BRCA2 mutation carriers. We found an increased risk of developing a first primary tumor (breast or ovarian) before 35 years of age for individuals who carried at least one No Ins‐72Pro haplotype (OR: 2.69; 95% CI: 1.15–6.29; P=0.022). We confirmed these data by a functional study in which we compared different p53 genotypes in relation to their apoptotic response after cell treatment with a cytotoxic drug (AraC). Our results revealed a decrease in p53 apoptotic rate associated with the No Ins‐72Pro haplotype. Hum Mutat 27(3), 242–248, 2006. © 2006 Wiley‐Liss, Inc.

Este artigo consiste em uma revisão de literatura temática com o objetivo de responder às seguintes questões de investigação: Como é o impacto empírico da educação empreendedora (EE) na intenção empreendedora (IE) no contexto dos estudantes universitários? Quais são as lacunas de investigação na literatura existente sobre o impacto da EE e da IE? Quais são as implicações teóricas e práticas das descobertas? As principais conclusões indicam que existem na literatura quatro tipos de impactos da EE na IE: 1) Efeito direto e positivo da EE na IE, 2) A EE não tem impacto na IE, 3) Efeito indireto da EE na IE através de variáveis mediadoras, 4) Efeito direto e positivo da EE sobre a IE, mas moderado por outras variáveis. Identificamos lacunas em quatro vertentes de pesquisa e fornecemos um exemplo de investigação prospectiva para colmatá-las com base na inclusão de estudantes com baixas intenções empreendedoras. Indicamos implicações práticas e teóricas.

The allohexaploid Aegilops species (2n = 6x = 42), Ae. neglecta 6x (UUX t X t NN), Ae. juvenalis (D c D c X c X c UU), and Ae. vavilovii (D c D c X c X c S s S s ) regularly form bivalents at metaphase I. However, in Ae. crassa 6x (D c D c X c X c DD) 0.27 quadrivalents per cell were observed probably as a consequence of the partial homology displayed by the D and D c genomes. Likewise, the synthetic amphiploid Ae. ventricosa-Secale cereale (DDNNRR) is fertile and displays a diploid-like behavior at metaphase I, despite its recent origin. The pattern of synapsis at late zygotene and pachytene in the natural and artificial allohexaploids was analyzed by whole-mount surface-spreading of synaptonemal complexes under an electron microscope. It revealed that chromosomes were mostly associated as bivalents in all cases, the mean of multivalents per nucleus ranging from 0.17 (Ae. neglecta 6x) to 1.03 (Ae. crassa 6x) in the natural species and 1.05 in the Ae. ventricosa-S. cereale amphiploid. It can be concluded that the mechanism controlling bivalent formation in these species and also in the synthetic amphiploid acts mainly at zygotene by restricting synapsis to homologous chromosomes, but also acts at pachytene by preventing chiasma formation in the homoeologous associations. These observations are discussed in relation to the origin and evolution of the mechanism of diploidization in the allopolyploid species of the Poaceae family.