Factors Affecting the Induction of Porphyria in the Laboratory Rat. Biochemical and Photobiological Studies Using Diethyl 1,4-dihydro-2,4,6-trimethyl-pyridine-3,5-dicarboxylate (DDC) as a Porphyrogenic Agent*

Porphyria induced by the fluorochrome, diethyl 1,4-dihydro-2,4,6-trimethyl py-ridine-3,5-dicarboxylate (DDC) has been studied in laboratory rats and the factors determining the pattern of porphyrin excretion have been assessed. Definitive studies demonstrating specific photosensitivity of the skin in the porphyric rats have been carried out.It has been established that the magnitude of porphyrin excretion as well as the type of porphyric pattern is dosage dependent. Increased fecal protoporphyrin output can occur without other evidence of porphyria at a low dosage level. As the drug dosage is increased, fecal and urinary coproporphyrin and finally urinary uroporphyrin values are additionally increased. These changes in porphyrin output have been explained on the current theory that DDC inhibits the incorporation of protoporphyrin into heme and the production of heme compounds so that by a positive feedback mechanism ALA synthetase is activated and excess urinary copro and uroporphyrin excretion occurs.The collidine derivative was well tolerated by animals receiving a conventional rat diet ad libitum, but in animals on purified diets a state of chronic nutrient deprivation precipitated acute toxicity. Toxic symptoms, associated with DDC intake at a high dosage level, included constipation, icterus, oliguria and premature death.The primary hepatic lesion of DDC-induced porphyria consisted in biliary hyperplasia with a surrounding mononuclear infiltrate. Discrete aggregation of protoporphyrin within the bile ducts and in the periductal inflammatory cells was localized by polarization and fluorescence microscopy. At autopsy the animals exhibiting toxic symptoms showed massive hepatic necrosis and renal tubular damage

Vascular Endothelial Growth Factor-Related Pathways in Hemato-Lymphoid Malignancies

Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies

Primakoff effect in eta-photoproduction off protons

We analyse data on forward eta-meson photoproduction off a proton target and extract the eta to gamma gamma decay width utilizing the Primakoff effect. The hadronic amplitude that enters into our analysis is strongly constrained because it is fixed from a global fit to available gamma p to p eta data for differential cross sections and polarizations. We compare our results with present information on the two-photon eta-decay from the literature. We provide predictions for future PrimEx experiments at Jefferson Laboratory in order to motivate further studies.Comment: 5 pages, 6 figures, gamma-gamma*-eta form factor included, version to appear in Eur. Phys. J. A

Patterns of cell cycle checkpoint deregulation associated with intrinsic molecular subtypes of human breast cancer cells

Genomic instability is a hallmark of breast cancer, contributes to tumor heterogeneity, and influences chemotherapy resistance. Although Gap 2 and mitotic checkpoints are thought to prevent genomic instability, the role of these checkpoints in breast cancer is poorly understood. Here, we assess the Gap 2 and mitotic checkpoint functions of 24 breast cancer and immortalized mammary epithelial cell lines representing four of the six intrinsic molecular subtypes of breast cancer. We found that patterns of cell cycle checkpoint deregulation were associated with the intrinsic molecular subtype of breast cancer cell lines. Specifically, the luminal B and basal-like cell lines harbored two molecularly distinct Gap 2/mitosis checkpoint defects (impairment of the decatenation Gap 2 checkpoint and the spindle assembly checkpoint, respectively). All subtypes of breast cancer cell lines examined displayed aberrant DNA synthesis/Gap 2/mitosis progression and the basal-like and claudin-low cell lines exhibited increased percentages of chromatid cohesion defects. Furthermore, a decatenation Gap 2 checkpoint gene expression signature identified in the cell line panel correlated with clinical outcomes in breast cancer patients, suggesting that breast tumors may also harbor defects in decatenation Gap 2 checkpoint function. Taken together, these data imply that pharmacological targeting of signaling pathways driving these phenotypes may lead to the development of novel personalized treatment strategies for the latter two subtypes which currently lack targeted therapeutic options because of their triple negative breast cancer status

Decision by sampling

We present a theory of decision by sampling (DbS) in which, in contrast with traditional models, there are no underlying psychoeconomic scales. Instead, we assume that an attribute’s subjective value is constructed from a series of binary, ordinal comparisons to a sample of attribute values drawn from memory and is its rank within the sample. We assume that the sample reflects both the immediate distribution of attribute values from the current decision’s context and also the background, real-world distribution of attribute values. DbS accounts for concave utility functions; losses looming larger than gains; hyperbolic temporal discounting; and the overestimation of small probabilities and the underestimation of large probabilities

First Observation of Coherent π0\pi^0 Production in Neutrino Nucleus Interactions with Eν<E_{\nu}< 2 GeV

The MiniBooNE experiment at Fermilab has amassed the largest sample to date of $\pi^0$s produced in neutral current (NC) neutrino-nucleus interactions at low energy. This paper reports a measurement of the momentum distribution of $\pi^0$s produced in mineral oil (CH$_2$) and the first observation of coherent $\pi^0$ production below 2 GeV. In the forward direction, the yield of events observed above the expectation for resonant production is attributed primarily to coherent production off carbon, but may also include a small contribution from diffractive production on hydrogen. Integrated over the MiniBooNE neutrino flux, the sum of the NC coherent and diffractive modes is found to be (19.5 $\pm$1.1 (stat) $\pm$2.5 (sys))% of all exclusive NC $\pi^0$ production at MiniBooNE. These measurements are of immediate utility because they quantify an important background to MiniBooNE's search for $\nu_{\mu} \to \nu_e$ oscillations.Comment: Submitted to Phys. Lett.

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results