A Dense Packing of Regular Tetrahedra

We construct a dense packing of regular tetrahedra, with packing density $D > >.7786157$.Comment: full color versio

A review of the Dividend Discount Model: from deterministic to stochastic models

This chapter presents a review of the dividend discount models starting from the basic models (Williams 1938, Gordon and Shapiro 1956) to more recent and complex models (Ghezzi and Piccardi 2003, Barbu et al. 2017, D'Amico and De Blasis 2018) with a focus on the modelling of the dividend process rather than the discounting factor, that is assumed constant in most of the models. The Chapter starts with an introduction of the basic valuation model with some general aspects to consider when performing the computation. Then, Section 1.3 presents the Gordon growth model (Gordon 1962) with some of its extensions (Malkiel 1963, Fuller and Hsia 1984, Molodovsky et al. 1965, Brooks and Helms 1990, Barsky and De Long 1993), and reports some empirical evidence. Extended reviews of the Gordon stock valuation model and its extensions can be found in Kamstra (2003) and Damodaran (2012). In Section 1.4, the focus is directed to more recent advancements which make us of the Markov chain to model the dividend process (Hurley and Johnson 1994, Yao 1997, Hurley and Johnson 1998, Ghezzi and Piccardi 2003, Barbu et al. 2017, D'Amico and De Blasis 2018). The advantage of these models is the possibility to obtain a different valuation that depends on the state of the dividend series, allowing the model to be closer to reality. In addition, these models permit to obtain a measure of the risk of the single stock or a portfolio of stocks

The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C

Opioids are some of the most efficacious analgesics used in humans. Prolonged administration of opioids, however, often causes the development of drug tolerance, thus limiting their effectiveness. To explore the molecular basis of those mechanisms that may contribute to opioid tolerance, we have isolated a cDNA for the human mu opioid receptor, the target of such opioid narcotics as morphine, codeine, methadone, and fentanyl. The receptor encoded by this cDNA is 400 amino acids long with 94% sequence similarity to the rat mu opioid receptor. Transient expression of this cDNA in COS-7 cells produced high-affinity binding sites to mu-selective agonists and antagonists. This receptor displays functional coupling to a recently cloned G-protein-activated K+ channel. When both proteins were expressed in Xenopus oocytes, functional desensitization developed upon repeated stimulation of the mu opioid receptor, as observed by a reduction in K+ current induced by the second mu receptor activation relative to that induced by the first. The extent of desensitization was potentiated by both the multifunctional calcium/calmodulin-dependent protein kinase and protein kinase C. These results demonstrate that kinase modulation is a molecular mechanism by which the desensitization of mu receptor signaling may be regulated at the cellular level, suggesting that this cellular mechanism may contribute to opioid tolerance in humans

WD + MS systems as the progenitor of SNe Ia

We show the initial and final parameter space for SNe Ia in a ($\log P^{\rm i}, M_{\rm 2}^{\rm i}$) plane and find that the positions of some famous recurrent novae, as well as a supersoft X-ray source (SSS), RX J0513.9-6951, are well explained by our model. The model can also explain the space velocity and mass of Tycho G, which is now suggested to be the companion star of Tycho's supernova. Our study indicates that the SSS, V Sge, might be the potential progenitor of supernovae like SN 2002ic if the delayed dynamical-instability model due to Han & Podsiadlowski (2006) is appropriate. Following the work of Meng, Chen & Han (2009), we found that the SD model (WD + MS) with an optically thick wind can explain the birth rate of supernovae like SN 2006X and reproduce the distribution of the color excess of SNe Ia. The model also predicts that at least 75% of all SNe Ia may show a polarization signal in their spectra.Comment: 6 pages, 2 figures, accepted for publication in Astrophysics & Space Science (Proceeding of the 4th Meeting on Hot Subdwarf Stars and Related Objects, edited by Zhanwen Han, Simon Jeffery & Philipp Podsiadlowski

A pilgrimage to gravity on GPUs

In this short review we present the developments over the last 5 decades that have led to the use of Graphics Processing Units (GPUs) for astrophysical simulations. Since the introduction of NVIDIA's Compute Unified Device Architecture (CUDA) in 2007 the GPU has become a valuable tool for N-body simulations and is so popular these days that almost all papers about high precision N-body simulations use methods that are accelerated by GPUs. With the GPU hardware becoming more advanced and being used for more advanced algorithms like gravitational tree-codes we see a bright future for GPU like hardware in computational astrophysics.Comment: To appear in: European Physical Journal "Special Topics" : "Computer Simulations on Graphics Processing Units" . 18 pages, 8 figure

FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates

The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the "Claw" for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation

Nanoliter high throughput quantitative PCR

Understanding biological complexity arising from patterns of gene expression requires accurate and precise measurement of RNA levels across large numbers of genes simultaneously. Real time PCR (RT-PCR) in a microtiter plate is the preferred method for quantitative transcriptional analysis but scaling RT-PCR to higher throughputs in this fluidic format is intrinsically limited by cost and logistic considerations. Hybridization microarrays measure the transcription of many thousands of genes simultaneously yet are limited by low sensitivity, dynamic range, accuracy and sample throughput. The hybrid approach described here combines the superior accuracy, precision and dynamic range of RT-PCR with the parallelism of a microarray in an array of 3072 real time, 33 nl polymerase chain reactions (RT-PCRs) the size of a microscope slide. RT-PCR is demonstrated with an accuracy and precision equivalent to the same assay in a 384-well microplate but in a 64-fold smaller reaction volume, a 24-fold higher analytical throughput and a workflow compatible with standard microplate protocols

Neuroprotective activity of ursodeoxycholic acid in CHMP2B Intron5 models of frontotemporal dementia

Frontotemporal dementia (FTD) is one of the most prevalent forms of early-onset dementia. It represents part of the FTD-Amyotrophic Lateral Sclerosis (ALS) spectrum, a continuum of genetically and pathologically overlapping disorders. FTD-causing mutations in CHMP2B, a gene encoding a core component of the heteromeric ESCRT-III Complex, lead to perturbed endosomal-lysosomal and autophagic trafficking with impaired proteostasis. While CHMP2B mutations are rare, dysfunctional endosomal-lysosomal signalling is common across the FTD-ALS spectrum. Using our established Drosophila and mammalian models of CHMP2BIntron5 induced FTD we demonstrate that the FDA-approved compound Ursodeoxycholic Acid (UDCA) conveys neuroprotection, downstream of endosomal-lysosomal dysfunction in both Drosophila and primary mammalian neurons. UDCA exhibited a dose dependent rescue of neuronal structure and function in Drosophila pan-neuronally expressing CHMP2BIntron5. Rescue of CHMP2BIntron5 dependent dendritic collapse and apoptosis with UDCA in rat primary neurons was also observed. UDCA failed to ameliorate aberrant accumulation of endosomal and autophagic organelles or ubiquitinated neuronal inclusions in both models. We demonstrate the neuroprotective activity of UDCA downstream of endosomal-lysosomal and autophagic dysfunction, delineating the molecular mode of action of UDCA and highlighting its potential as a therapeutic for the treatment of FTD-ALS spectrum disorders