A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.

Seventy-five percent of breast cancers are estrogen receptor α positive (ER(+)). Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER(+) tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER(+) tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER(+) PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.

An evaluation of the Swiss staging model for hypothermia using case reports from the literature.

BACKGROUND: Core body temperature is used to stage and guide the management of hypothermic patients, however obtaining accurate measurements of core temperature is challenging, especially in the pre-hospital context. The Swiss staging model for hypothermia uses clinical indicators to stage hypothermia. The proposed temperature range for clinical stage 1 is <35-32 °C (95-90 °F), for stage 2, <32-28 °C (<90-82 °F) for stage 3, <28-24 °C (<82-75 °F), and for stage 4 below 24 °C (75 °F). However, the evidence relating these temperature ranges to the clinical stages needs to be strengthened. METHODS: Medline was used to retrieve data on as many cases of accidental hypothermia (core body temperature <35 °C (95 °F)) as possible. Cases of therapeutic or neonatal hypothermia and those with confounders or insufficient data were excluded. To evaluate the Swiss staging model for hypothermia, we estimated the percentage of those patients who were correctly classified and compared the theoretical with the observed ranges of temperatures for each clinical stage. The number of rescue collapses was also recorded. RESULTS: We analysed 183 cases; the median temperature for the sample was 25.2 °C (IQR 22-28). 95 of the 183 patients (51.9 %; 95 % CI = 44.7 %-59.2 %) were correctly classified, while the temperature was overestimated in 36 patients (19.7 %; 95 % CI = 13.9 %-25.4 %). We observed important overlaps among the four stage groups with respect to core temperature, the lowest observed temperature being 28.1 °C for Stage 1, 22 °C for Stage 2, 19.3 °C for Stage 3, and 13.7 °C for stage 4. CONCLUSION: Predicting core body temperature using clinical indicators is a difficult task. Despite the inherent limitations of our study, it increases the strength of the evidence linking the clinical hypothermia stage to core temperature. Decreasing the thresholds of temperatures distinguishing the different stages would allow a reduction in the number of cases where body temperature is overestimated, avoiding some potentially negative consequences for the management of hypothermic patients.

Spinal Cord T-Cell Infiltration in the Rat Spared Nerve Injury Model: A Time Course Study.

The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the spared nerve injury (SNI) model of neuropathic pain in Sprague Dawley adult male rats to assess proliferation, and/or protein/gene expression levels for microglia (Iba1), T-lymphocytes (CD2) and cytotoxic T-lymphocytes (CD8). In the dorsal horn ipsilateral to SNI, Iba1 and BrdU stainings revealed microglial reactivity and proliferation, respectively, with different durations. Iba1 expression peaked at D4 and D7 at the mRNA and protein level, respectively, and was long-lasting. Proliferation occurred almost exclusively in Iba1 positive cells and peaked at D2. Gene expression observation by RT-qPCR array suggested that T-lymphocytes attracting chemokines were upregulated after SNI in rat spinal cord but only a few CD2/CD8 positive cells were found. A pronounced infiltration of CD2/CD8 positive T-cells was seen in the spinal cord injury (SCI) model used as a positive control for lymphocyte infiltration. Under these experimental conditions, we show early and long-lasting microglia reactivity in the spinal cord after SNI, but no lymphocyte infiltration was found.

An integrated model of adoption and development of e-commerce in companies

Since the mid-1990s researchers have sought to understand why some firms embark on e-commerceoperations on the Internet while others prefer to wait and see how events unfold. We still have todetermine which variables contribute to explaining the extent to which firms use e-commerce, giventhat to date the literature has not yet offered conclusive evidence on this question. The current workaims to provide an integrated vision of the set of factors influencing the e-commerce adoptionprocess. We use a sample of 2,038 firms of all types that trade their products either with otherorganizations or with end-consumers.

Некоторые наблюдения по поводу построения компьютерного морфологического анализатора марийского языка. [Problems in writing a two-level model of Mari morphology]

The article describes some concrete problems that were encountered when writing a two-level model of Mari morphology. Mari is an agglutinative Finno-Ugric language spoken in Russia by about 600 000 people. The work was begun in the 1980s on the basis of K. Koskenniemi’s Two-Level Morphology (1983), but in the latest stage R. Beesley’s and L. Karttunen’s Finite State Morphology (2003) was used. Many of the problems described in the article concern the inexplicitness of the rules in Mari grammars and the lack of information about the exact distribution of some suffixes, e.g. enclitics. The Mari grammars usually give complete paradigms for a few unproblematic verb stems, whereas the difficult or unclear forms of certain verbs are only superficially discussed. Another example of phenomena that are poorly described in grammars is the way suffixes with an initial sibilant combine to stems ending in a sibilant. The help of informants and searches from electronic corpora were used to overcome such difficulties in the development of the two-level model of Mari. The variation of the order of plural markers, case suffixes and possessive suffixes is a typical feature of Mari. The morphotactic rules constructed for Mari declensional forms tend to be recursive and their productivity must be limited by some technical device, such as filters. In the present model, certain plural markers were treated like nouns. The positional and functional versatility of the possessive suffixes can be regarded as the most challenging phenomenon in attempts to formalize the Mari morphology. Cyrillic orthography, which was used in the model, also caused problems. For instance, a Cyrillic letter may represent a sequence of two sounds, the first being part of the word stem while the other belongs to a suffix. In some cases, letters for voiced consonants are also generalized to represent voiceless consonants. Such orthographical conventions distance a morphological model based on orthography from the actual (morpho)phonological processes in the language.

Special issue on evolving the e-marketing mindset towards the social web model - Editorial Part 2

In the previous issue of IJEMR, we introduced the general framework and the main ideas justifying this special editorial project. To avoid repetition of the background themes to the current issue, the reader should consult the previous edition. Here, we present the second part of contributions selected for publication.

Special issue on evolving the e-marketing mindset towards the social web model - Editorial Part 1

Con este proyecto editorial nuestro objetivo es promover un campo de investigación clave en la comercialización de hoy, es decir, la evolución de la mentalidad e-marketing hacia el nuevo modelo de web social.

Analysis of the structural and electronic properties of 1-(5-Hydroxymethyl - 4 -[ 5 - (5-oxo-5-piperidin-1-yl-penta-1,3dienyl)-benzo[1,3]dioxol-2-yl] -tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4dione molecule

The structural and electronic properties of 1-(5-Hydroxymethyl - 4 -[ 5 - (5-oxo-5-piperidin- 1 -yl-penta- 1,3 -dienyl)-benzo [1,3] dioxol- 2 -yl]-tetrahydro -furan-2 -yl)-5-methy l-1Hpyrimidine-2,4dione (AHE) molecule have been investigated theoretically by performing density functional theory (DFT), and semi empirical molecular orbital calculations. The geometry of the molecule is optimized at the level of Austin Model 1 (AM1), and the electronic properties and relative energies of the molecules have been calculated by density functional theory in the ground state. The resultant dipole moment of the AHE molecule is about 2.6 and 2.3 Debyes by AM1 and DFT methods respectively, This property of AHE makes it an active molecule with its environment, that is AHE molecule may interacts with its environment strongly in solution.

Value creation through sponsorship in electronic sports

The objective of this thesis was to study value creation through sponsor-ship in a new emerging electronic sports environment. Sub-questions were formulated which helped in finding answers to the main research question. Theory of traditional sports and practice of electronic sports were compared with each other in order to find out how theories of tradi-tional sports fare in the new environment. B2B-relationship model of Actors, resources and activities is used in this thesis to help in clarifying the different variables used in electronic sports sponsorship environment. The empirical research was conducted via interviews with the managers working in electronic sports environment. One of the main conclusions is that relationship management is really important.. Actors in electronic sports need to find and create win-win-win situations. This means that they need to benefit the actors in sponsoring relationship and also the community.

An improved experimental model for peripheral neuropathy in rats

A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.

Implementing the OPTIMAL model : the impact on students' motivation in an elementary school games environment

Optimal challenge occurs when an individual perceives the challenge of the task to be equaled or matched by his or her own skill level (Csikszentmihalyi, 1990). The purpose of this study was to test the impact of the OPTIMAL model on physical education students' motivation and perceptions of optimal challenge across four games categories (i. e. target, batting/fielding, net/wall, invasion). Enjoyment, competence, student goal orientation and activity level were examined in relation to the OPTIMAL model. A total of 22 (17 M; 5 F) students and their parents provided informed consent to take part in the study and were taught four OPTIMAL lessons and four non-OPTIMAL lessons ranging across the four different games categories by their own teacher. All students completed the Task and Ego in Sport Questionnaire (TEOSQ; Duda & Whitehead, 1998), the Intrinsic Motivation Inventory (IMI; McAuley, Duncan, & Tanmien, 1987) and the Children's Perception of Optimal Challenge Instrument (CPOCI; Mandigo, 2001). Sixteen students (two each lesson) were observed by using the System for Observing Fitness Instruction Time tool (SOFTT; McKenzie, 2002). As well, they participated in a structured interview which took place after each lesson was completed. Quantitative results concluded that no overall significant difference was found in motivational outcomes when comparing OPTIMAL and non-OPTIMAL lessons. However, when the lessons were broken down into games categories, significant differences emerged. Levels of perceived competence were found to be higher in non-OPTIMAL batting/fielding lessons compared to OPTIMAL lessons, whereas levels of enjoyment and perceived competence were found to be higher in OPTIMAL invasion lessons in comparison to non-OPTIMAL invasion lessons. Qualitative results revealed significance in feehngs of skill/challenge balance, enjoyment and competence in the OPTIMAL lessons. Moreover, a significance of practically twice the active movement time percentage was found in OPTIMAL lessons in comparison to non-OPTIMAL lessons.

Calculation of the magnetic field penetration depth for high-Tc cuprate superconductors based on the Interlayer Pair Tunneling model /

In this work, the magnetic field penetration depth for high-Tc cuprate superconductors is calculated using a recent Interlayer Pair Tunneling (ILPT) model proposed by Chakravarty, Sudb0, Anderson, and Strong [1] to explain high temperature superconductivity. This model involves a "hopping" of Cooper pairs between layers of the unit cell which acts to amplify the pairing mechanism within the planes themselves. Recent work has shown that this model can account reasonably well for the isotope effect and the dependence of Tc on nonmagnetic in-plane impurities [2] , as well as the Knight shift curves [3] and the presence of a magnetic peak in the neutron scattering intensity [4]. In the latter case, Yin et al. emphasize that the pair tunneling must be the dominant pairing mechanism in the high-Tc cuprates in order to capture the features found in experiments. The goal of this work is to determine whether or not the ILPT model can account for the experimental observations of the magnetic field penetration depth in YBa2Cu307_a7. Calculations are performed in the weak and strong coupling limits, and the efi"ects of both small and large strengths of interlayer pair tunneling are investigated. Furthermore, as a follow up to the penetration depth calculations, both the neutron scattering intensity and the Knight shift are calculated within the ILPT formalism. The aim is to determine if the ILPT model can yield results consistent with experiments performed for these properties. The results for all three thermodynamic properties considered are not consistent with the notion that the interlayer pair tunneling must be the dominate pairing mechanism in these high-Tc cuprate superconductors. Instead, it is found that reasonable agreement with experiments is obtained for small strengths of pair tunneling, and that large pair tunneling yields results which do not resemble those of the experiments.

Motivational model of problem drinking for men and women /

This thesis tested a path model of the relationships of reasons for drinking and reasons for limiting drinking with consumption of alcohol and drinking problems. It was hypothesized that reasons for drinking would be composed of positively and negatively reinforcing reasons, and that reasons for limiting drinking would be composed of personal and social reasons. Problem drinking was operationalized as consisting of two factors, consumption and drinking problems, with a positive relationship between the two. It was predicted that positively and negatively reinforcing reasons for drinking would be associated with heavier consumption and, in turn, more drinking problems, through level of consumption. Negatively reinforcing reasons were also predicted to be associated with drinking problems directly, independent of level of consumption. It was hypothesized that reasons for limiting drinking would be associated with lower levels of consumption and would be related to fewer drinking problems, through level of consumption. Finally, among women, reasons for limiting drinking were expected to be associated with drinking problems directly, independent of level of consumption. The sample, was taken from the second phase of the Niagara Young Aduh Health Study, a community sample of young adult men and women. Measurement models of reasons for drinking, reasons for limiting drinking, and problem drinking were tested using Confirmatory Factor Analysis. After adequate fit of each measurement model was obtained, the complete structural model, with all hypothesized paths, was tested for goodness of fit. Cross-group equality constraints were imposed on all models to test for gender differences. The results provided evidence supporting the hypothesized structure of reasons for drinking and problem drinking. A single factor model of reasons for limiting drinking was used in the analyses because a two-factor model was inadequate. Support was obtained for the structural model. For example, the resuhs revealed independent influences of Positively Reinforcing Reasons for Drinking, Negatively Reinforcing Reasons for Drinking, and Reasons for Limiting Drinking on consumption. In addition. Negatively Reinforcing Reasons helped to account for Drinking Problems independent of the amount of alcohol consumed. Although an additional path from Reasons for Limiting Drinking to Drinking Problems was hypothesized for women, it was of marginal significance and did not improve the model's fit. As a result, no sex differences in the model were found. This may be a result of the convergence of drinking patterns for men and women. Furthermore, it is suggested that gender differences may only be found in clinical samples of problem drinkers, where the relative level of consumption for women and men is similar.

Aspergillus flavus infections in Galleria mellonella : a pathogen-host model system for the study of emerging diseases

To study emerging diseases, I employed a model pathogen-host system involving infections of insect larvae with the opportunistic fungus Aspergillus flavus, providing insight into three mechanisms ofpathogen evolution namely de novo mutation, genome decay, and virulence factoracquisition In Chapter 2 as a foundational experiment, A. flavus was serially propagated through insects to study the evolution of an opportunistic pathogen during repeated exposure to a single host. While A. flavus displayed de novo phenotypic alterations, namely decreased saprobic capacity, analysis of genotypic variation in Chapter 3 signified a host-imposed bottleneck on the pathogen population, emphasizing the host's role in shaping pathogen population structure. Described in Chapter 4, the serial passage scheme enabled the isolation of an A. flavus cysteine/methionine auxotroph with characteristics reminiscent of an obligate insect pathogen, suggesting that lost biosynthetic capacity may restrict host range based on nutrient availability and provide selection pressure for further evolution. As outlined in Chapter 6, cysteine/methionine auxotrophy had the pleiotrophic effect of increasing virulence factor production, affording the slow-growing auxotroph with a modified pathogenic strategy such that virulence was not reduced. Moreover in Chapter 7, transformation with a virulence factor from a facultative insect pathogen failed to increase virulence, demonstrating the necessity of an appropriate genetic background for virulence factor acquisition to instigate pathogen evolution.