A novel cell culture model for studying differentiation and apoptosis in the mouse mammary gland.

BACKGROUND: This paper describes the derivation and characterization of a novel, conditionally immortal mammary epithelial cell line named KIM-2. These cells were derived from mid-pregnant mammary glands of a mouse harbouring one to two copies of a transgene comprised of the ovine beta-lactoglobulin milk protein gene promoter, driving expression of a temperature-sensitive variant of simian virus-40 (SV40) large T antigen (T-Ag). RESULTS: KIM-2 cells have a characteristic luminal epithelial cell morphology and a stable, nontransformed phenotype at the semipermissive temperature of 37 degrees C. In contrast, at the permissive temperature of 33 degrees C the cells have an elongated spindle-like morphology and become transformed after prolonged culture. Differentiation of KIM-2 cells at 37 degrees C, in response to lactogenic hormones, results in the formation of polarized dome-like structures with tight junctions. This is accompanied by expression of the milk protein genes that encode beta-casein and whey acidic protein (WAP), and activation of the prolactin signalling molecule, signal transducer and activator of transcription (STAT)5. Fully differentiated KIM-2 cultures at 37 degrees C become dependent on lactogenic hormones for survival and undergo extensive apoptosis upon hormone withdrawal, as indicated by nuclear morphology and flow cytometric analysis. KIM-2 cells can be genetically modified by stable transfection and clonal lines isolated that retain the characteristics of untransfected cells. CONCLUSION: KIM-2 cells are a valuable addition, therefore, to currently available lines of mammary epithelial cells. Their capacity for extensive differentiation in the absence of exogenously added basement membrane, and ability to undergo apoptosis in response to physiological signals will provide an invaluable model system for the study of signal transduction pathways and transcriptional regulatory mechanisms that control differentiation and involution in the mammary gland

Deleterious Effects of Intermittent Recombinant Parathyroid Hormone on Cartilage Formation in a Rabbit Microfracture Model: a Preliminary Study

Intermittent parathyroid hormone administration can enhance fracture healing in an animal model. Despite the success of exogenous parathyroid hormone on fracture healing and spine fusion, few studies have examined the role of parathyroid hormone on cartilage formation. We determined the effects of intermittent parathyroid hormone on cartilage formation in a rabbit microfracture model of cartilage regeneration. Twelve rabbits were divided into three equal groups: (1) microfracture alone, (2) microfracture + parathyroid hormone daily for 7 days, and (3) microfracture + parathyroid hormone for 28 days. Nonoperated contralateral knees were used as controls. The animals were sacrificed at 3 months and gross and histologic analysis was performed. The microfracture alone group demonstrated the most healing on gross and histologic analysis. Treatment with either 1 or 4 weeks of parathyroid hormone inhibited cartilage formation. Although discouraging from a cartilage repair point of view, this study suggests that the role parathyroid hormone administration has in clinical fracture healing must be examined carefully. Although parathyroid hormone is beneficial to promote healing in spine fusion and midshaft fractures, its deleterious effects on cartilage formation suggests that it may have adverse effects on the outcomes of periarticular fractures such as tibial plateau injuries that require cartilage healing for a successful clinical outcome

Associated production of neutral toppion with a pair of heavy quarks in γγ\gamma\gamma collisions

We have studied a neutral toppion production process $\gamma\gamma\to f\bar{f}\Pi_{t}^{0}(f=t,b)$ in the topcolor-assisted technicolor(TC2) model. We find that the cross section of $\gamma\gamma\to t\bar{t}\Pi_{t}^{0}$ is much larger than that of $\gamma\gamma\to b\bar{b}\Pi_{t}^{0}$. On the other hand, the cross section can be obviously enhanced with the increasing of c.m.energy. With $\sqrt{s}=1600$ GeV, the cross section of $t\bar{t}\Pi_t^0$ production can reach the level of a few fb. The results show that $\gamma\gamma\to t\bar{t}\Pi^0_t \to t\bar{t}(t\bar{c})$ is the most ideal channel to detect neutral toppion due to the clean SM background. With such sufficient signals and clean background, neutral toppion could be detected at TESLA with high c.m.energy.Comment: 11 pages, 5 figure

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

The economics of Theocracy

This paper models theocracy as a regime where the clergy in power retains knowledge of the cost of political production but which is potentially incompetent or corrupt. This is contrasted with a secular regime where government is contracted out to a secular ruler, and hence the church loses the possibility to observe costs and creates for itself a hidden-information agency problem. The church is free to choose between regimes – a make-or-buy choice – and we look for the range of environmental parameters that are most conducive to the superiority of theocracy and therefore to its occurrence and persistence, despite its disabilities. Numerical solution of the model indicates that the optimal environment for a theocracy is likely to be one in which the “bad” (high-cost) state is disastrously bad but the probability of its occurrence is not very high. A broad review of the historical evidence yields some suggestive support to the predictions of the model. Finally, the model is shown to be applicable to the make-or-buy-government choices of other groups, such as organized labor and the military

Bayesian Based Comment Spam Defending Tool

Spam messes up user's inbox, consumes network resources and spread worms and viruses. Spam is flooding of unsolicited, unwanted e mail. Spam in blogs is called blog spam or comment spam.It is done by posting comments or flooding spams to the services such as blogs, forums,news,email archives and guestbooks. Blog spams generally appears on guestbooks or comment pages where spammers fill a comment box with spam words. In addition to wasting user's time with unwanted comments, spam also consumes a lot of bandwidth. In this paper, we propose a software tool to prevent such blog spams by using Bayesian Algorithm based technique. It is derived from Bayes' Theorem. It gives an output which has a probability that any comment is spam, given that it has certain words in it. With using our past entries and a comment entry, this value is obtained and compared with a threshold value to find if it exceeds the threshold value or not. By using this concept, we developed a software tool to block comment spam. The experimental results show that the Bayesian based tool is working well. This paper has the major findings and their significance of blog spam filter.Comment: 14 Pages,4 Figures, International Journal of Network Security & Its Applications (IJNSA), Vol.2, No.4, October 201

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant inheritance of germline mutations in the bone morphogenetic protein receptor type 2 (<it>BMPR2</it>) gene are a major risk factor for pulmonary arterial hypertension (PAH). While previous studies demonstrated a difference in severity between <it>BMPR2 </it>mutation carriers and noncarriers, it is likely disease severity is not equal among <it>BMPR2 </it>mutations. We hypothesized that patients with missense <it>BMPR2 </it>mutations have more severe disease than those with truncating mutations.</p> <p>Methods</p> <p>Testing for <it>BMPR2 </it>mutations was performed in 169 patients with PAH (125 with a family history of PAH and 44 with sporadic disease). Of the 106 patients with a detectable <it>BMPR2 </it>mutation, lymphocytes were available in 96 to functionally assess the nonsense-mediated decay pathway of RNA surveillance. Phenotypic characteristics were compared between <it>BMPR2 </it>mutation carriers and noncarriers, as well as between those carriers with a missense versus truncating mutation.</p> <p>Results</p> <p>While there was a statistically significant difference in age at diagnosis between carriers and noncarriers, subgroup analysis revealed this to be the case only for females. Among carriers, there was no difference in age at diagnosis, death, or survival according to exonic location of the <it>BMPR2 </it>mutation. However, patients with missense mutations had statistically significant younger ages at diagnosis and death, as well as shorter survival from diagnosis to death or lung transplantation than those with truncating mutations. Consistent with this data, the majority of missense mutations were penetrant prior to age 36 years, while the majority of truncating mutations were penetrant after age 36 years.</p> <p>Conclusion</p> <p>In this cohort, <it>BMPR2 </it>mutation carriers have more severe PAH disease than noncarriers, but this is only the case for females. Among carriers, patients with missense mutations that escape nonsense-mediated decay have more severe disease than those with truncating mutations. These findings suggest that treatment and prevention strategies directed specifically at <it>BMPR2 </it>pathway defects may need to vary according to the type of mutation.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012