Inhibition of histone deacetylase as a treatment for cardiac hypertrophy

The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.Board of Regents, University of Texas Syste

Clicks or bricks? Online shopping adoption in Australia

Purpose: This research identifies and ranks the decision factors associated with online shopping adoption in Australia. Design/Methodology/Approach: Primary data for this study was collected with self-administered questionnaires and analysed using EFA and logit regression. Findings: The following factors, ranked in order of importance, influence online shopping behaviour in Australia: perceived risk, service quality, website factors, brand image, product variety and Australian product loyalty. The findings also show that demographic characteristics also influence the probability that Australian consumers will shop online. Originality/value: This is the first empirical study in which the decision factors influencing Australian consumers’ decisions to shop online are examined. The research contributes to the empirical literature on online shopping from a theoretical perspective as the modelling framework can be used to analyse online shopping behaviour in different cultural settings. Longitudinal studies based on the modelling framework can also be undertaken to identify emerging decision factors and to track the changes in importance of the current factors. The results will also enable retailers to make informed decisions on their existing or future shopping channels

Hybrid density functional theory description of N- and C-doping of NiO

The large intrinsic bandgap of NiO hinders its potential application as a photocatalyst under visible-light irradiation. In this study, we have performed first-principles screened exchange hybrid density functional theory with the HSE06 functional calculations of N- and C-doped NiO to investigate the effect of doping on the electronic structure of NiO. C-doping at an oxygen site induces gap states due to the dopant, the positions of which suggest that the top of the valence band is made up primarily of C 2p-derived states with some Ni 3d contributions, and the lowest-energy empty state is in the middle of the gap. This leads to an effective bandgap of 1.7 eV, which is of potential interest for photocatalytic applications. N-doping induces comparatively little dopant-Ni 3d interactions, but results in similar positions of dopant-induced states, i.e., the top of the valence band is made up of dopant 2p states and the lowest unoccupied state is the empty gap state derived from the dopant, leading to bandgap narrowing. With the hybrid density functional theory (DFT) results available, we discuss issues with the DFT corrected for on-site Coulomb description of these systems

Fitness-driven deactivation in network evolution

Individual nodes in evolving real-world networks typically experience growth and decay --- that is, the popularity and influence of individuals peaks and then fades. In this paper, we study this phenomenon via an intrinsic nodal fitness function and an intuitive aging mechanism. Each node of the network is endowed with a fitness which represents its activity. All the nodes have two discrete stages: active and inactive. The evolution of the network combines the addition of new active nodes randomly connected to existing active ones and the deactivation of old active nodes with possibility inversely proportional to their fitnesses. We obtain a structured exponential network when the fitness distribution of the individuals is homogeneous and a structured scale-free network with heterogeneous fitness distributions. Furthermore, we recover two universal scaling laws of the clustering coefficient for both cases, $C(k) \sim k^{-1}$ and $C \sim n^{-1}$, where $k$ and $n$ refer to the node degree and the number of active individuals, respectively. These results offer a new simple description of the growth and aging of networks where intrinsic features of individual nodes drive their popularity, and hence degree.Comment: IoP Styl

Modeling transcription factor binding events to DNA using a random walker/jumper representation on a 1D/2D lattice with different affinity sites

Surviving in a diverse environment requires corresponding organism responses. At the cellular level, such adjustment relies on the transcription factors (TFs) which must rapidly find their target sequences amidst a vast amount of non-relevant sequences on DNA molecules. Whether these transcription factors locate their target sites through a 1D or 3D pathway is still a matter of speculation. It has been suggested that the optimum search time is when the protein equally shares its search time between 1D and 3D diffusions. In this paper, we study the above problem using a Monte Carlo simulation by considering a very simple physical model. A 1D strip, representing a DNA, with a number of low affinity sites, corresponding to non-target sites, and high affinity sites, corresponding to target sites, is considered and later extended to a 2D strip. We study the 1D and 3D exploration pathways, and combinations of the two modes by considering three different types of molecules: a walker that randomly walks along the strip with no dissociation; a jumper that represents dissociation and then re-association of a TF with the strip at later time at a distant site; and a hopper that is similar to the jumper but it dissociates and then re-associates at a faster rate than the jumper. We analyze the final probability distribution of molecules for each case and find that TFs can locate their targets fast enough even if they spend 15% of their search time diffusing freely in the solution. This indeed agrees with recent experimental results obtained by Elf et al. 2007 and is in contrast with theoretical expectation.Comment: 24 pages, 9 figure

Magnetic Properties of Linear Chain Systems: Metamagnetism of Single Crystal Co(pyridine)₂CI₂

The metamagnetic behavior of the low temperature properties of single crystal Co(pyridine)2Cl2 is discussed. At 1.25 K oriented single crystals exhibit a two-step metamagnetic transition at applied fields ~0.8 and 1.6 kG along the b-axis, a single transition at ~0.7 kG for applied fields along the a* axis, and a single transition at ~4.2 kG for an applied field along the c axis. Just above the transition fields a moment of 2µB/Co atom is measured for B0 parallel to the a* axis or b axis, and 0.4µB/Co atom is measured for the B0 parallel to the c axis. A large field dependent moment is observed at high fields. Many features of this compound closely mirror the behavior of CoCl2-2H20. However, the Co(pyridine)2Cl 2 has a much smaller interchain exchange, so that many features can be examined at lower fields. The basic features are consistent with a six-sublattice model for the ordered antiferromagnetic system. Measurements of magnetic moment versus temperature show that Co(pyridine)2Cl 2 does not obey a Curie-Weiss law even at relatively high temperatures

Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group

Who is accessing community lateral flow device testing and why:Characteristics and motivations of individuals participating in COVID-19 community testing in two English local authority areas

BACKGROUND: Antigen testing using lateral flow devices (LFDs) plays an important role in the management of the novel coronavirus pandemic of 2019 (COVID-19) by rapidly identifying individuals who are asymptomatically carrying high levels of the virus. By January 2021, LFD community testing sites were set up across English local authority areas to support the management and containment of regional COVID-19 cases, initially targeting essential workers unable to work from home during the national lockdown. This study aimed to examine the characteristics and motivations of individuals accessing community LFD testing across two local authority areas (LAAs) in the South West of England. METHODS: Data were collected as part of a service evaluation from December 22(nd) 2020 until March 15(th) 2021 for two LAAs. Demographic and postcode data were collected from an online test appointment booking platform and the National Health Service testing service online system, with data accessed from Public Health England. An online survey was sent to individuals who made a testing appointment at an LAA1 site using the online booking platform, consisting of 12 questions to collect data on individual’s motivations for and experiences of testing. RESULTS: Data were available for individuals who completed 12,516 tests in LAA1 and 12,327 tests in LAA2. Most individuals who engaged with testing were female, working age, white, and worked as early years or education staff, health and social care staff, and supermarket or food production staff. 1249 individuals completed the survey with 60% of respondents reported getting tested for work-related reasons. Individuals first heard about LFD testing through various channels including work, media, and word of mouth, and decided to get tested based on the ease and convenience of testing, workplace communications, and to identify asymptomatic cases to help stop the spread. Most tests were completed by individuals living in less deprived areas based on national deciles of deprivation. CONCLUSIONS: While national and local COVID-19 testing strategies have evolved, community and personal LFD testing remains a crucial pillar of the testing strategy. Future studies should collect quantitative and qualitative data from residents to most effectively shape testing offers based on the needs and preferences of their population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12986-4