1,833 research outputs found

    Role of HOX Genes in Stem Cell Differentiation and Cancer.

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    HOX genes encode an evolutionarily conserved set of transcription factors that control how the phenotype of an organism becomes organized during development based on its genetic makeup. For example, in bilaterian-type animals, HOX genes are organized in gene clusters that encode anatomic segment identity, that is, whether the embryo will form with bilateral symmetry with a head (anterior), tail (posterior), back (dorsal), and belly (ventral). Although HOX genes are known to regulate stem cell (SC) differentiation and HOX genes are dysregulated in cancer, the mechanisms by which dysregulation of HOX genes in SCs causes cancer development is not fully understood. Therefore, the purpose of this manuscript was (i) to review the role of HOX genes in SC differentiation, particularly in embryonic, adult tissue-specific, and induced pluripotent SC, and (ii) to investigate how dysregulated HOX genes in SCs are responsible for the development of colorectal cancer (CRC) and acute myeloid leukemia (AML). We analyzed HOX gene expression in CRC and AML using information from The Cancer Genome Atlas study. Finally, we reviewed the literature on HOX genes and related therapeutics that might help us understand ways to develop SC-specific therapies that target aberrant HOX gene expression that contributes to cancer development

    The Effect of Ordering Method on Consumer Return Intentions

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    With the rise of Covid-19, mobile ordering has become one of the most popular ways to get food. At its height, Covid-19 caused restaurants to shut down and forced businesses to move to a more mobile and delivery-friendly plan. Now, venues for concerts, large events, and sports have started to offer the option of mobile ordering food to be delivered directly to your seat. Mobile ordering has made the food service industry even more accessible; however, it has also brought to light the issue of tipping. Traditionally, tipping was only done at full-service restaurants. Now, businesses like Starbucks, Mcdonald\u27s, and DoorDash ask you to tip before you have received the food when you mobile order. This paper examines the relationship between the platform consumers use to order and consumer return intentions. It also examines whether tip amount and tip likelihood have moderating effects

    Heat pipes for wing leading edges of hypersonic vehicles

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    Wing leading edge heat pipes were conceptually designed for three types of vehicle: an entry research vehicle, aero-space plane, and advanced shuttle. A full scale, internally instrumented sodium/Hastelloy X heat pipe was successfully designed and fabricated for the advanced shuttle application. The 69.4 inch long heat pipe reduces peak leading edge temperatures from 3500 F to 1800 F. It is internally instrumented with thermocouples and pressure transducers to measure sodium vapor qualities. Large thermal gradients and consequently large thermal stresses, which have the potential of limiting heat pipe life, were predicted to occur during startup. A test stand and test plan were developed for subsequent testing of this heat pipe. Heat pipe manufacturing technology was advanced during this program, including the development of an innovative technique for wick installation

    An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development.

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    APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes

    Catastrophic Risk Evaluation

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    A body of empirical evidence has shown that many managers would welcome new ways of highlighting catastrophic consequences, as well as means to evaluating decision situations involving high risks. When events occur frequently and their consequences are not severe, it is relatively simple to calculate the risk exposure of an organisation, as well as a reasonable premium when an insurance transaction is made. The usual methods rely on variations of the principle of maximising the expected utility (PMEU). When, on the other hand, the frequency of damages is low, the situation is considerably more difficult, especially if catastrophic events occur. When the quality of estimates is poor, e.g., when evaluating low-probability/high-consequence risks, the customary use of quantitative rules together with overprecise data could be harmful as well as misleading. This work extends the risk evaluation process by the integration of procedures for handling vague and numerically imprecise probabilities and utilities. The shortcomings of PMEU, and of utility theory in general, can in part be compensated for by the introduction of risk constraints. We point out some problematic features of the evaluations performed using utility theory. We also criticise the demand for precise data in situations where none is available. As an alternative to traditional models, we suggest a method for the evaluation of risks when the information at hand is numerically imprecise. The method includes procedures that allow for interval statements and comparisons, and thereby it does not require the use of numerically precise statements of probability, cost, or utility in a general sense. In order to attain a reasonable level of security, and because it has been shown that managers tend to focus on large negative losses, it is argued that a risk constraint should be imposed on the analysis. The strategies are evaluated relative to a set of such constraints considering how risky the strategies are

    Comment on ``Density-matrix renormalization-group method for excited states''

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    In a Physical Review B paper Chandross and Hicks claim that an analysis of the density-density correlation function in the dimerised Hubbard model of polyacetylene indicates that the optical exciton is bound, and that a previous study by Boman and Bursill that concluded otherwise was incorrect due to numerical innacuracy. We show that the method used in our original paper was numerically sound and well established in the literature. We also show that, when the scaling with lattice size is analysed, the interpretation of the density-density correlation function adopted by Chandross and Hicks in fact implies that the optical exciton is unbound.Comment: RevTeX, 10 pages, 4 eps figures fixed and included now in tex

    The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells

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    Background: Tumorigenesis is driven by stem cell (SC) overpopulation. BecauseALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA)signaling, we studied RA signaling in normal and malignant colonic SCs.Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonicSCs dysregulation of RA signaling contributes to SC overpopulation and colorectalcancer (CRC) development.Methods: We analyzed normal and malignant colonic tissues and CRC cell linesto see if retinoid receptors (RXR &RAR) are exclusively expressed in ALDH+ SCs,and if RA signaling changes during CRC development. We determined whether RAsignaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation,and population size.Results: RXR &RAR were expressed in ALDH+ colonic SCs, but not in MCM2+proliferative cells. Western blotting/immunostaining of CRCs revealed that RAsignaling components become overexpressed in parallel with ALDH overexpression,which coincides with the known overpopulation of ALDH+ SCs that occurs during,and drives, CRC development. Treatment of SCs with all-trans retinoic acid (ATRA)decreased proliferation, sphere formation and ALDH+ SC population size, and induceddifferentiation along the neuroendocrine cell (NEC) lineage.Conclusions: Retinoid signaling, by regulating ALDH+ colonic CSCs, decreases SCproliferation, sphere formation, and population size, and increases SC differentiation toNECs. Dysregulation of RA signaling in colonic SCs likely contributes to overpopulationof ALDH+ SCs and CRC growth.Implications: That retinoid receptors RXR and RAR are selectively expressed inALDH+ SCs indicates RA signaling mainly occurs via ALDH+ SCs, which provides amechanism to selectively target CSCs. © 2018 Impact Journals LLC. All rights reserved

    The Age of Armor

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    The project group created a twelve-minute videodocumentary about the evolution of armor from Ancient Greece through the Medieval period to the Renaissance with respect to society, technology and warfare. The videodocumentary is based on historical research, compiled by the group in a substantial report. The documentary, to be displayed at the Higgins Armory Museum in Worcester, MA, incorporates images of the museum\u27s artifacts, historical and modern artwork, footage of armored re-enactors, and an original script and musical score

    Electron-lattice relaxation, and soliton structures and their interactions in polyenes

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    Density matrix renormalisation group calculations of a suitably parametrised model of long polyenes (polyacetylene oligomers), which incorporates both long range Coulomb interactions and adiabatic lattice relaxation, are presented. The triplet and 2Ag states are found to have a 2-soliton and 4-soliton form, respectively, both with large relaxation energies. The 1Bu state forms an exciton-polaron and has a very small relaxation energy. The relaxed energy of the 2Ag state lies below that of the 1Bu state. The soliton/anti-soliton pairs are bound.Comment: RevTeX, 5 pages, 4 eps figures included using epsf. To appear in Physical Review Letters. Fig. 1 fixed u
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