Representations of an integer by some quaternary and octonary quadratic forms

In this paper we consider certain quaternary quadratic forms and octonary quadratic forms and by using the theory of modular forms, we find formulae for the number of representations of a positive integer by these quadratic forms.Comment: 20 pages, 4 tables. arXiv admin note: text overlap with arXiv:1607.0380

Ultracold dense gas of deeply bound heteronuclear molecules

Recently, the quest for an ultracold and dense ensemble of polar molecules has attracted strong interest. Polar molecules have bright prospects for novel quantum gases with long-range and anisotropic interactions, for quantum information science, and for precision measurements. However, high-density clouds of ultracold polar molecules have so far not been produced. Here, we report a key step towards this goal. Starting from an ultracold dense gas of heteronuclear 40K-87Rb Feshbach molecules with typical binding energies of a few hundred kHz and a negligible dipole moment, we coherently transfer these molecules into a vibrational level of the ground-state molecular potential bound by >10 GHz. We thereby increase the binding energy and the expected dipole moment of the 40K-87Rb molecules by more than four orders of magnitude in a single transfer step. Starting with a single initial state prepared with Feshbach association, we achieve a transfer efficiency of 84%. While dipolar effects are not yet observable, the presented technique can be extended to access much more deeply bound vibrational levels and ultimately those exhibiting a significant dipole moment. The preparation of an ultracold quantum gas of polar molecules might therefore come within experimental reach.Comment: 5 pages, 5 figure

Activated Magnetospheres of Magnetars

Like the solar corona, the external magnetic field of magnetars is twisted by surface motions of the star. The twist energy is dissipated over time. We discuss the theory of this activity and its observational status. (1) Theory predicts that the magnetosphere tends to untwist in a peculiar way: a bundle of electric currents (the "j-bundle") is formed with a sharp boundary, which shrinks toward the magnetic dipole axis. Recent observations of shrinking hot spots on magnetars are consistent with this behavior. (2) Continual discharge fills the j-bundle with electron-positron plasma, maintaining a nonthermal corona around the neutron star. The corona outside a few stellar radii strongly interacts with the stellar radiation and forms a "radiatively locked" outflow with a high e+- multiplicity. The locked plasma annihilates near the apexes of the closed magnetic field lines. (3) New radiative-transfer simulations suggest a simple mechanism that shapes the observed X-ray spectrum from 0.1 keV to 1 MeV: part of the thermal X-rays emitted by the neutron star are reflected from the outer corona and then upscattered by the inner relativistic outflow in the j-bundle, producing a beam of hard X-rays.Comment: 23 pages, 7 figures; review chapter in the proceedings of ICREA Workshop on the High-Energy Emission from Pulsars and Their Systems, Sant Cugat, Spain, April 201

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Mapping Genetically Compensatory Pathways from Synthetic Lethal Interactions in Yeast

Background: Synthetic lethal genetic interaction analysis has been successfully applied to predicting the functions of genes and their pathway identities. In the context of synthetic lethal interaction data alone, the global similarity of synthetic lethal interaction patterns between two genes is used to predict gene function. With physical interaction data, such as proteinprotein interactions, the enrichment of physical interactions within subsets of genes and the enrichment of synthetic lethal interactions between those subsets of genes are used as an indication of compensatory pathways. Result: In this paper, we propose a method of mapping genetically compensatory pathways from synthetic lethal interactions. Our method is designed to discover pairs of gene-sets in which synthetic lethal interactions are depleted among the genes in an individual set and where such gene-set pairs are connected by many synthetic lethal interactions. By its nature, our method could select compensatory pathway pairs that buffer the deleterious effect of the failure of either one, without the need of physical interaction data. By focusing on compensatory pathway pairs where genes in each individual pathway have a highly homogenous cellular function, we show that many cellular functions have genetically compensatory properties. Conclusion: We conclude that synthetic lethal interaction data are a powerful source to map genetically compensatory pathways, especially in systems lacking physical interaction information, and that the cellular function network contain

The R337H mutation in TP53 and breast cancer in Brazil

<p>Abstract</p> <p>Background</p> <p>Germline mutations in p53 are associated with the Li-Fraumeni Syndrome which is characterized by childhood cancers, including pediatric adrenal cortical carcinomas and early onset breast cancer. The high incidence of adrenal cortical carcinomas in southern Brazil is mostly attributed to the <it>R337H </it>mutation in <it>TP53</it>. The relatively high population frequency of this mutation in southern Brazil, along with the clustering of early onset breast cancer in Li-Frameni families, suggests this mutation may also be a low-penetrance breast cancer susceptibility polymorphism.</p> <p>Methods</p> <p>We undertook this study to evaluate the frequency of the <it>R337H </it>mutation in breast cancer patients from Rio de Janeiro, Brazil. <it>R337H </it>mutation status was determined in 390 unselected breast cases and 324 controls identified from clinics in Rio de Janeiro, Brazil using a PCR-based assay.</p> <p>Results</p> <p>Two of the breast cancer cases (0.5%) and none of the controls carried the mutation. Both cases had an early age at diagnosis (< 40 years old) and a family history of breast and other cancers.</p> <p>Conclusions</p> <p>These data suggest genetic screening of young onset breast cancer patients should include testing for the <it>R337H </it>mutation.</p

Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria

<p>Abstract</p> <p>Background</p> <p>Several non-governmental organisations (NGOs) are promoting the use of <it>Artemisia annua </it>teas as a home-based treatment for malaria in situations where conventional treatments are not available. There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.</p> <p>Method</p> <p>A questionnaire about the cultivation of <it>A. annua</it>, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda. Some of the respondents were then selected purposively for more in-depth semi-structured interviews.</p> <p>Results</p> <p>Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought. Overall about 3,000 cases of presumed malaria had been treated with <it>A. annua </it>teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy. The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey. Two miscarriages were reported in pregnant patients. Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using <it>A. annua </it>tea to treat illnesses other than malaria.</p> <p>Conclusions</p> <p>Local cultivation and preparation of <it>A. annua </it>are feasible where growing conditions are appropriate. Few adverse events were reported even in children and pregnant women. Where ACT is in short supply, it would make sense to save it for young children, while using <it>A. annua </it>infusions to treat older patients who are at lower risk. An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.</p

Fluorescent Gold Nanoprobes for the Sensitive and Selective Detection for Hg2+

A simple, cost-effective yet rapid and sensitive sensor for on-site and real-time Hg2+ detection based on bovine serum albumin functionalized fluorescent gold nanoparticles as novel and environmentally friendly fluorescent probes was developed. Using this probe, aqueous Hg2+ can be detected at 0.1 nM in a facile way based on fluorescence quenching. This probe was also applied to determine the Hg2+ in the lake samples, and the results demonstrate low interference and high sensitivity