336 research outputs found
Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells
Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragmentâbased approach to create new flexible Gâquadruplex (G4) DNAâinteractive small molecules with good calculated oral drugâlike properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)âstop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a doseâ and DNA sequenceâdependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the Gâquartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4âČâ(4,4âČâ(1,3âphenylene)bis(1Hâ1,2,3âtriazoleâ4,1âdiyl))bis(1âmethylquinolinâ1âium) (1âd) showed the greater activity. Importantly, doseâresponse curves show that 1âd is cytotoxic in the human colon cancer HTâ29 cell line enriched in cancer stemâlike cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells
Pressure effects on the structural and superconducting transitions in LaâCoâSnââ
La3Co4Sn13 is a superconducting material with transition temperature at Tc = 2.70 K, which
presents a superlattice structural transition at T
â â 150 K, a common feature for this class of
compounds. However, for this material, it is not clear that at T
â
the lattice distortions arise from
a charge density wave (CDW) or from a distinct microscopic origin. Interestingly, it has been
suggested in isostructural non-magnetic intermetallic compounds that T
â
can be suppressed to zero
temperature, by combining chemical and external pressure, and a quantum critical point is argued
to be observed near these critical doping/pressure. Our study shows that application of pressure
on single-crystalline La3Co4Sn13 enhances Tc and decreases T
â
. We observe thermal hysteresis
loops for cooling/heating cycles around T
â
for P & 0.6 GPa, in electrical resistivity measurements,
which are not seen in x-ray diffraction data. The hysteresis in electrical measurements may be due
to the pinning of the CDW phase to impurities/defects, while the superlattice structural transition
maintains its ambient pressure second-order transition nature under pressure. From our experiments
we estimate that T
â
vanishes at around 5.5 GPa, though no quantum critical behavior is observed
up to 2.53 GPa
How did the latest increase in fees in England affect student enrolment and inequality?
This paper presents a first analysis of the increase of undergraduate tuition fees to ÂŁ9,000 (âŹ11.000) in English higher education in 2012. I use a semi-experimental research design to estimate the effect of the reforms, based on student enrolment data drawn from the Higher Education Statistics Agency (HESA). Taking into account possible anticipation effects of the fee increase, I find that enrolment declined by 15 % in the treated groups as a result of the tuition fee increase. This number is almost three times higher than what previous studies have found, and may represent a serious long term cost for the English economy. The decline in enrolments is particularly pronounced for students in older age groups and students from the service class and the middle class. No effect is visible for students from the working class, indicating that the reforms did not lead to a much-feared increase in class bias in higher education enrolment. The reforms also seem not to have exacerbated ethnic inequality in higher education, as all ethnic groups were negatively affected by the reforms. These results are consistent with earlier research in the United States and the United Kingdom, although they expand our understanding of student price responsiveness in other important ways. The paper argues that younger and older students face different costs and benefits. Older students may be less certain about their benefits, and therefore be more sensitive towards price increases. The strong decrease in mature learners may require a policy response, taking into account these differing incentives
Effects of adenosine A2A receptor activation and alanyl-glutamine in Clostridium difficile toxin-induced ileitis in rabbits and cecitis in mice
<p>Abstract</p> <p>Background</p> <p>Severe <it>Clostridium difficile </it>toxin-induced enteritis is characterized by exuberant intestinal tissue inflammation, epithelial disruption and diarrhea. Adenosine, through its action on the adenosine A<sub>2A </sub>receptor, prevents neutrophillic adhesion and oxidative burst and inhibits inflammatory cytokine production. Alanyl-glutamine enhances intestinal mucosal repair and decreases apoptosis of enterocytes. This study investigates the protection from enteritis by combination therapy with ATL 370, an adenosine A<sub>2A </sub>receptor agonist, and alanyl-glutamine in a rabbit and murine intestinal loop models of <it>C. difficile </it>toxin A-induced epithelial injury.</p> <p>Methods</p> <p>Toxin A with or without alanyl-glutamine was administered intraluminally to rabbit ileal or murine cecal loops. Animals were also given either PBS or ATL 370 parenterally. Ileal tissues were examined for secretion, histopathology, apoptosis, Cxcl1/KC and IL-10.</p> <p>Results</p> <p>ATL 370 decreased ileal secretion and histopathologic changes in loops treated with Toxin A. These effects were reversed by the A<sub>2A </sub>receptor antagonist, SCH 58261, in a dose-dependent manner. The combination of ATL 370 and alanyl-glutamine significantly further decreased ileal secretion, mucosal injury and apoptosis more than loops treated with either drug alone. ATL 370 and alanyl-glutamine also decreased intestinal tissue KC and IL-10.</p> <p>Conclusions</p> <p>Combination therapy with an adenosine A<sub>2A </sub>receptor agonist and alanyl-glutamine is effective in reversing <it>C. difficile </it>toxin A-induced epithelial injury, inflammation, secretion and apoptosis in animals and has therapeutic potential for the management of <it>C. difficile </it>infection.</p
TOLKIN â Tree of Life Knowledge and Information Network: Filling a Gap for Collaborative Research in Biological Systematics
The development of biological informatics infrastructure capable of supporting growing data management and analysis environments is an increasing need within the systematics biology community. Although significant progress has been made in recent years on developing new algorithms and tools for analyzing and visualizing large phylogenetic data and trees, implementation of these resources is often carried out by bioinformatics experts, using one-off scripts. Therefore, a gap exists in providing data management support for a large set of non-technical users. The TOLKIN project (Tree of Life Knowledge and Information Network) addresses this need by supporting capabilities to manage, integrate, and provide public access to molecular, morphological, and biocollections data and research outcomes through a collaborative, web application. This data management framework allows aggregation and import of sequences, underlying documentation about their source, including vouchers, tissues, and DNA extraction. It combines features of LIMS and workflow environments by supporting management at the level of individual observations, sequences, and specimens, as well as assembly and versioning of data sets used in phylogenetic inference. As a web application, the system provides multi-user support that obviates current practices of sharing data sets as files or spreadsheets via email
The holographic principle
There is strong evidence that the area of any surface limits the information
content of adjacent spacetime regions, at 10^(69) bits per square meter. We
review the developments that have led to the recognition of this entropy bound,
placing special emphasis on the quantum properties of black holes. The
construction of light-sheets, which associate relevant spacetime regions to any
given surface, is discussed in detail. We explain how the bound is tested and
demonstrate its validity in a wide range of examples.
A universal relation between geometry and information is thus uncovered. It
has yet to be explained. The holographic principle asserts that its origin must
lie in the number of fundamental degrees of freedom involved in a unified
description of spacetime and matter. It must be manifest in an underlying
quantum theory of gravity. We survey some successes and challenges in
implementing the holographic principle.Comment: 52 pages, 10 figures, invited review for Rev. Mod. Phys; v2:
reference adde
An update of malaria infection and anaemia in adults in Buea, Cameroon
<p>Abstract</p> <p>Background</p> <p>Anaemia is caused by many factors in developing countries including malaria. We compared anaemia rates in patients with malaria parasitaemia to that of patients without malaria parasitaemia.</p> <p>Findings</p> <p>A cross-sectional study was carried out from November 2007 to July 2008 in health units in Buea, Cameroon. Adult patients with fever or history of fever were included in the study. Information on socio-demographic variables and other variables was collected using a questionnaire. Malaria parasitaemia status was determined by microscopy using Giemsa stained thick blood smears. Haemoglobin levels were determined by the microhaematocrit technique.</p> <p>The study population consisted of 250 adult patients with a mean age of 29.31 years (SD = 10.63) and 59.44% were females. 25.60% of the patients had malaria parasitaemia while 14.80% had anaemia (haemoglobin < 11 g/dl). Logistic regression revealed that those with malaria parasitaemia had more anaemia compared to those without malaria parasitaemia(OR = 4.33, 95%CI = 1.21-15.43, p = 0.02) after adjusting for age, sex, rural residence, socioeconomic status, use of antimalarials, use of insecticide treated nets(ITN) and white blood cell count.</p> <p>Conclusions</p> <p>In adult patients with fever in this setting, malaria parasitaemia contributes to anaemia and is of public health impact. Our results also provide a baseline prevalence for malaria parasitaemia in febrile adults in health units in this setting.</p
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