The Oct3/4 gene, a POU family transcription factor, has been noted as being specifically expressed in embryonic stem cells and in tumor cells but not in cells of differentiated tissues. With the ability to isolate adult human stem cells it became possible to test for the expression of Oct3/4 gene in adult stem cells and to test the stem cell theory of carcinogenesis. Using antibodies and PCR primers we tested human breast, liver, pancreas, kidney, mesenchyme and gastric stem cells, the cancer cell lines HeLa and MCF-7 and human, dog and rat tumors for Oct4 expression. The results indicate that adult human stem cells, immortalized non-tumorigenic cells and tumor cells and cell lines, but not differentiated cells, express Oct4. Oct4 is expressed in a few cells found in the basal layer of human skin epidermis. The data demonstrate that adult stem cells maintain expression of Oct4, consistent with the stem cell hypothesis of carcinogenesis.

We calculate-for the first time in three-flavor lattice QCD-the hadronic matrix elements of all five local operators that contribute to neutral B 0 -and B s -meson mixing in and beyond the Standard Model. We present a complete error budget for each matrix element and also provide the full set of correlations among the matrix elements. We also present the corresponding bag parameters and their correlations, as well as specific combinations of the mixing matrix elements that enter the expression for the neutral B-meson width difference. We obtain the most precise determination to date of the SU(3)-breaking ratio ξ = 1.206(18)(6), where the second error stems from the omission of charm sea quarks, while the first encompasses all other uncertainties. The threefold reduction in total uncertainty, relative to the 2013 Flavor Lattice Averaging Group results, tightens the constraint from B mixing on the Cabibbo-Kobayashi-Maskawa (CKM) unitarity triangle. Our calculation employs gauge-field ensembles generated by the MILC Collaboration with four lattice spacings and pion masses close to the physical value. We use the asqtad-improved staggered action for the light valence quarks, and the Fermilab method for the bottom quark. We use heavy-light meson chiral perturbation theory modified to include lattice-spacing effects to extrapolate the five matrix elements to the physical point. We combine our results with experimental measurements of the neutral B-meson oscillation frequencies to determine the CKM matrix elements |V td | = 8.00(34)(8) × 10 −3 , |V ts | = 39.0(1.2)(0.4) × 10 −3 , and |V td /V ts | = 0.2052(31)(10), which differ from CKM-unitarity expectations by about 2σ. These results and others from flavor-changing-neutral currents point towards an emerging tension between weak processes that are mediated at the loop and tree levels.

The axial coupling of the nucleon, g, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of g makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome: contamination of g from excited states must be controlled in the calculations and statistical precision must be improved markedly. Here we use an unconventional method inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a g value of 1.271 ± 0.013, which has a precision of about one per cent.

The Feynman-Hellmann theorem can be derived from the long Euclidean-time limit of correlation functions determined with functional derivatives of the partition function. Using this insight, we fully develop an improved method for computing matrix elements of external currents utilizing only two-point correlation functions. Our method applies to matrix elements of any external bilinear current, including nonzero momentum transfer, flavor-changing, and two or more current insertion matrix elements. The ability to identify and control all the systematic uncertainties in the analysis of the correlation functions stems from the unique time dependence of the ground-state matrix elements and the fact that all excited states and contact terms are Euclidean-time dependent. We demonstrate the utility of our method with a calculation of the nucleon axial charge using gradient-flowed domain-wall valence quarks on the N f ¼ 2 þ 1 þ 1 MILC highly improved staggered quark ensemble with lattice spacing and pion mass of approximately 0.15 fm and 310 MeV respectively. We show full control over excited-state systematics with the new method and obtain a value of g A ¼ 1.213ð26Þ with a quark-mass-dependent renormalization coefficient.

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Two types of human breast epithelial cells (HBEC) have been characterized. In contrast to Type II HBEC, which express basal epithelial cell phenotypes, Type I HBEC are deficient in gap junctional intercellular communication and are capable of anchorage-independent growth and of expressing luminal epithelial cell markers, estrogen receptors, and stem cell characteristics (i.e. the ability to differentiate into other cell types and to form budding/ductal organoids on Matrigel). A comparative study of these two types of cells has revealed a high susceptibility of Type I HBEC to immortalization by SV40 large T antigen, although both types of cells are equally capable of acquiring an extended life span (bypassing senescence) after transfection with SV40. The immortalization was accompanied by elevation of a low level of telomerase activity in the parental cells after mid-passage ( approximately 60 cumulative population doubling levels). Thus HBEC do have a low level of telomerase activity, and Type I HBEC with stem cell characteristics are more susceptible to telomerase activation and immortalization, a mechanism which might qualify them as target cells for breast carcinogenesis. The immortalized Type I HBEC can be converted to highly tumorigenic cells by further treatment with X rays (2 Gy x 2) and transfection with a mutated ERBB2 (also known as NEU) oncogene, resulting in the expression of p185(ERBB2) which is tyrosine phosphorylated.

Observation of neutrinoless double beta decay, a lepton number violating process that has been proposed to clarify the nature of neutrino masses, has spawned an enormous world-wide experimental effort. Relating nuclear decay rates to high-energy, beyond the Standard Model (BSM) physics requires detailed knowledge of non-perturbative QCD effects. Using lattice QCD, we compute the necessary matrix elements of short-range operators, which arise due to heavy BSM mediators, that contribute to this decay via the leading order π − → π + exchange diagrams. Utilizing our result and taking advantage of effective field theory methods will allow for model-independent calculations of the relevant two-nucleon decay, which may then be used as input for nuclear many-body calculations of the relevant experimental decays. Contributions from short-range operators may prove to be equally important to, or even more important than, those from long-range Majorana neutrino exchange.Introduction.-Neutrinoless double beta decay (0νββ) is a process that, if observed, would reveal violations of symmetries fundamental to the Standard Model, and would guarantee that neutrinos have nonzero Majorana mass [1, 2]. Such decays can probe physics beyond the electroweak scale and expose a source of leptonnumber (L) violation which may explain the observed matter-antimatter asymmetry in the universe [3,4]. Existing and planned experiments will constrain this novel nuclear decay [5][6][7][8][9][10][11][12][13][14][15][16], but the interpretation of the resulting decay rates or limits as constraints on new physics poses a tremendous theoretical challenge.The most widely discussed mechanism for 0νββ is that of a light Majorana neutrino, which can propagate a long distance within a nucleus. However, if the mechanism involves a heavy scale, Λ ββ , the resulting L-violating process can be short-ranged. While naïvely short-range operators are suppressed compared to long-range interactions due to the heavy mediator propagator, in the case of 0νββ, the long-range interaction requires a helicity flip and is proportional to the mass of the light neutrino. In a standard seesaw scenario [17][18][19][20][21], this light neutrino mass is similarly suppressed by the same large mass scale, so the relative importance of long-versus short-range contributions is dependent upon the particle physics model under consideration and in general cannot be determined until the nuclear matrix elements for both types of processes are computed.Both long-and short-range mechanisms present substantial theoretical challenges if we hope to connect high energy physics with experimentally observed decay rates. The former case is difficult because one must understand long-distance nuclear correlations. In the latter case the short-distance physics is masked by QCD effects, requiring non-perturbative methods to match few-nucleon matrix elements to Standard Model operators.Effective field theory (EFT) arguments show that at leading order (LO) in the Standard Model, there are nine local four-...

Hanahan and Weinberg (2000, Cell 100: 57-70) listed "hallmarks" of cancer that must be considered in order to understand the underlying determinants of carcinogenesis: (a) self-sufficiency in growth signals; (b) insensitivity to growth-inhibitory (antigrowth) signals; (c) evasion of programmed cell death (apoptosis); (d) limitedless replicative potential; (e) sustained angiogenesis; and (f) tissue invasion and metastasis. While these are important phenotypic markers, important concepts--the role of pluripotent stem cells and gap junctional intercellular communication (GJIC)--must be brought into this analysis of carcinogenesis. Carcinogenesis is a multistage, multimechanism process consisting of a single cell that has been irreversibly blocked from terminal differentiation (the initiation stage). The promotion phase is a potentially reversible or interruptible clonal expansion of the initiated cell by a combination of growth stimulation and inhibition of apoptosis. When the expanded initiated cells accrue sufficient mutations and epigenetic alterations to become growth stimulus independent and resistant to growth inhibitors and apoptosis, to have unlimited replicative potential and invasive and metastatic phenotypes, then the progression phase has been achieved. The hypothesis that integrates these hallmarks is that the stem cell and its early progenitor cell are the target cells for the initiation event. These cells are naturally immortal and become mortal only when they are induced to terminally differentiate and lose their telomerase activity. These two types of initiated cells are suppressed by either secreted negative growth regulators (the stem cells) or GJIC (the early initiated progenitor cells). Promoters inhibit either the secreted growth inhibitor to initiated stem cells or GJIC between the initiated progenitor cells and the normal progenitor cells. When a stable resistance to the secreted negative growth regulator or permanent downregulation of GJIC has occurred, the cell has entered the progression phase. These two new concepts contradict the current paradigm that the first phase of carcinogenesis is the immortalization of a normal cell followed by its neoplastic transformation. Our hypothesis is that the first stage of carcinogenesis must prevent the "mortalization" or terminal differentiation of a naturally immortal cell. Chemoprevention and chemotherapeutic implications suggest that one must induce connexin genes in initiated stem cells and restore GJIC in initiated early progenitor cells.