On the Statistical Distribution of Epidermal Papillomata in Mice

IN a previous investigation reported from this laboratory (Ball and McCarter, 1960) it was noted that tumours produced in the skin of the CFW mouse by treatment with 7,12-dimethylbenz(a)anthracene (DMBA) and croton oil, were not distributed among the mice in accordance with the expected Poisson's distribution. Animals bearing no tumours and those bearing many were much more numerous than expected. A quantitative analysis of induced primary adenomatous pulmonary tumours in mice was reported by Polissar and Shimkin (1954). They showed that the occurrence of such tumours was subject to Poisson's distribution and that deviations from this distribution could be attributed to heterogeneity of susceptibility in the animals. We have now analyzed the data obtained in our laboratory in three populations of mice undergoing epidermal carcinogenesis. MATERIALS AND METHODS Strain CFW.-These mice were females, purchased from Carworth Farms Inc., New City, New York. They were housed in groups of 10 in acrylic plastic boxes with stainless steel tops. The bedding was sawdust. Water and Purina Fox Chow Cubes were freely available. Strain CFW/D.-This strain originated when, through error, a male was included among the female CFW mice purchased from the supplier in 1958. Since that time, brother-sister mating has been carried out with a view to obtaining a single inbred line. Litters selected for brother-sister mating were chosen on the basis of health, number in the litter and even distribution of the sexes and not for sensitivity to carcinogenesis. The mice were in the thirteenth and fourteenth inbred generations when used. They were cared for as described above. Strain I.-This strain was obtained several years ago through the kindness of Dr. H. B. Andervont. The mice had been mated brother-to-sister for 71 to 72 generations when the experiment was begun. Chemicals. 7,1 2-dimethylbenz(a)anthracene and benzo((a)pyrene were obtained from Eastman Organic Chemicals. Croton oil was obtained from Bush and Co., Canada. Paraffin oil viscosity 125/135 NF was a product of Fisher Scientific Co., Montreal, Canada. Meprobamate (Miltown) was kindly supplied by Dr. F. M

Electronic density of states derived from thermodynamic critical field curves for underdoped La-Sr-Cu-O

Thermodynamic critical field curves have been measured for $La_{2-x}Sr_{x}CuO_{4+\delta}$ over the full range of carrier concentrations where superconductivity occurs in order to determine changes in the normal state density of states with carrier concentration. There is a substantial window in the $H-T$ plane where the measurements are possible because the samples are both thermodynamically reversible and the temperature is low enough that vortex fluctuations are not important. In this window, the data fit Hao-Clem rather well, so this model is used to determine $H_c$ and $\kappa_c$ for each temperature and carrier concentration. Using N(0) and the ratio of the energy gap to transition temperature, $\Delta (0)/k_BT_c$, as fitting parameters, the $H_c vs T$ curves give $\Delta (0)/k_BT_c \sim 2.0$ over the whole range of $x$. Values of N(0) remain rather constant in the optimum-doped and overdoped regime, but drops quickly toward zero in the underdoped regime.

Classical generalized constant coupling model for geometrically frustrated antiferromagnets

A generalized constant coupling approximation for classical geometrically frustrated antiferromagnets is presented. Starting from a frustrated unit we introduce the interactions with the surrounding units in terms of an internal effective field which is fixed by a self consistency condition. Results for the magnetic susceptibility and specific heat are compared with Monte Carlo data for the classical Heisenberg model for the pyrochlore and kagome lattices. The predictions for the susceptibility are found to be essentially exact, and the corresponding predictions for the specific heat are found to be in very good agreement with the Monte Carlo results.Comment: 4 pages, 3 figures, 2 columns. Discussion about the zero T value of the pyrochlore specific heat correcte

One-pot Synthesis of Lactams Using Domino Reactions: Combination of Schmidt Reaction with Sakuri and Aldol Reaction

A series of domino reactions in which the intramolecular Schmidt reaction is combined with either a Sakurai reaction, an aldol reaction, or both is reported. The Sakurai reaction of an allylsilane with an azido-containing enone under Lewis acidic conditions followed by protonation of the resulting titanium enolate species allowed for a subsequent intramolecular Schmidt reaction. Alternatively, the intermediate titanium enolate could undergo an aldol reaction, followed by the intramolecular Schmidt reaction to form lactam products with multiple stereogenic centers. The stereochemical features of the titanium enolate aldol reaction with several 3-azidoaldehyde substrates during this domino process is discussed

Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair

Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ. Thus, we aim to develop scaled down mini-chambers as simplified in vitro simulation systems, to bridge the gap between two-dimensional (2D) cell cultures on structured substrates and three-dimensional (3D) tissue culture. The mini-chambers were manipulated to systematically simulate and evaluate the influences of gravity, topography, fluid flow, and scaffold dimension on three exemplary cell models that play a role in CNS repair (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a tubular scaffold created by rolling up a microstructured membrane. Since we use CNS myelinating cultures, we can confirm that the scaffold does not affect neural cell differentiation. It was found that heterogeneous cell distribution within the tubular constructs was caused by a combination of gravity, fluid flow, topography, and scaffold configuration, while cell survival was influenced by scaffold length, porosity, and thickness. This research demonstrates that the mini-chambers represent a viable, novel, scale down approach for the evaluation of complex 3D scaffolds as well as providing a microbioprocessing strategy for tissue engineering and the potential repair of SCI

Gamma-ray and radio tests of the e+e- excess from DM annihilations

PAMELA and ATIC recently reported an excess in e+e- cosmic rays. We show that if it is due to Dark Matter annihilations, the associated gamma-ray flux and the synchrotron emission produced by e+e- in the galactic magnetic field violate HESS and radio observations of the galactic center and HESS observations of dwarf Spheroidals, unless the DM density profile is significantly less steep than the benchmark NFW and Einasto profiles.Comment: 16 pages, 4 figures; v2: normalizations fixed in Table 2 and typos corrected (no changes in the analysis nor the results), some references and comments added; v3: minor additions, matches published versio

Decaying Dark Matter in Supersymmetric Model and Cosmic-Ray Observations

We study cosmic-rays in decaying dark matter scenario, assuming that the dark matter is the lightest superparticle and it decays through a R-parity violating operator. We calculate the fluxes of cosmic-rays from the decay of the dark matter and those from the standard astrophysical phenomena in the same propagation model using the GALPROP package. We reevaluate the preferred parameters characterizing standard astrophysical cosmic-ray sources with taking account of the effects of dark matter decay. We show that, if energetic leptons are produced by the decay of the dark matter, the fluxes of cosmic-ray positron and electron can be in good agreements with both PAMELA and Fermi-LAT data in wide parameter region. It is also discussed that, in the case where sizable number of hadrons are also produced by the decay of the dark matter, the mass of the dark matter is constrained to be less than 200-300 GeV in order to avoid the overproduction of anti-proton. We also show that the cosmic gamma-ray flux can be consistent with the results of Fermi-LAT observation if the mass of the dark matter is smaller than nearly 4 TeV.Comment: 24 pages, 5 figure

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer

BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P=0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P=0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P=0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P=0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins