Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase

DNA methyltransferase 1 (Dnmt1) has a central role in copying the pattern of DNA methylation after replication which is one manifestation of epigenetic inheritance. With oligonculeotide substrates we show that mouse Dnmt1 has a 30- to 40-fold preference for hemimethylated DNA that is almost lost after addition of fully methylated oligonucleotides. Using long hemimethylated DNA substrates that carry defined methylation patterns and bisulfite analysis of the methylation reaction products, we show a 15-fold preference for hemimethylated CG sites. Dnmt1 moves along the DNA in a random walk methylating hemimethylated substrates with high processivity (>50 sites are visited on average which corresponds to linear diffusion over 6000 bp). The frequency of skipping sites is very low (<0.3%) and there is no detectable flanking sequence preference. CGCTC sites tend to terminate the processive methylation of DNA by Dnmt1. Unmethylated DNA is modified non-processively with a preference for methylation at CCGG sites. We simulate the propagation of methylation patterns using a stochastic model with the specificity of Dnmt1 observed here and conclude that either methylation of several sites is required to propagate the methylation information over several cellular generations or additional epigenetic information must be used

Conduction Mechanism and Dielectric Properties in Polyaniline/Titanium Dioxide Composites

The conductivity and dielectric properties of polyaniline (PANI) and PANI/TiO2 composites have been studied over a temperature range (313-393 K) and frequency range (25 Hz- 50 MHz). The nature of temperature and frequency-dependent conductivity can be explained by Jonscher’s universal power law and used to find the related parameters such as frequency exponent (s), dc conductivity (σdc), and crossover frequency (ωH). Besides, the frequency exponent analysis through a distinct model suggests that the conduction occurred through small polaron tunnelling in all compositions and at different temperatures. On the other hand, the enthalpy of migration (Hm), dissociation enthalpy of cation from its indigenous location alongside a compensating center (Hf), and the activation energy were also calculated using the Arrhenius relation. The temperature-dependent dc conductivity was examined in the framework of the theoretical model; Mott’s variable range hopping model (VRH) and experimental results were in good agreement with the 3-dimensional VRH model. As a function of temperature, dielectric constants (ε’ and ε”) increase while decreasing with an increasing dopant. Being such a high dielectric constant value, these composites can be used as frequency converters, modulators, and dielectric amplifiers

Polyaniline Chromium Nitrate Composites: Influence of Chromium Nitrate on Conductivity and Thermal Stability of Polyaniline

Thermal stability and electrical conductivity are the key to the technological feasibility and sustainability of conductingpolymers (CPs) and their composites in real-time applications. Notably, the impact of filler loading on above mentionedparameters of CPs needs to be examined and addressed with facile and easily accessible techniques. In the present study,Polyaniline (PANI) /chromium nitrate composites have been prepared via in situ polymerization of aniline through thechemical oxidative polymerization route. After that, the conductivity and thermal stability of PANI have been investigated atdifferent weight percentage loadings of chromium nitrate viz 5, 10, 20, and 40 % in the composite materials.The morphological and structural analysis of the pristine and composite samples were executed with Scanning electronmicroscopy (SEM), Fourier transforms infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) techniques. Thermalanalysis of proposed composites is carried out using the thermogravimetric analysis (TGA) method to evaluate variouskinetic parameters. The TGA thermogram and different calculated parameters revealed that the composites were morethermally stable than pristine PANI and that the composite having 20 wt % of chromium nitrate is thermally the most stable.The DC electrical conductivity data shows that PANI loaded with 20% chromium nitrate has the highest conductivity. Thisincrement in conductivity and thermal stability of the composites opens the path for many applications, such as sensors andelectronics

Theoretical analysis of relativistic energy corrections, partition function and thermodynamic properties of spherically confined hydrogen atom

The relativistic energy corrections for the spherically confined hydrogen with penetrable wall are calculated for various orbitals as a function of pressure and confinement radius. The relativistic corrections at high pressures of the order of 108–109 atm are found to be more than thousand times higher than the corresponding values for the free atom. For calculating the energy eigenvalues, the efficient Numerov method is adopted. The partition function and other thermodynamic properties are also calculated for temperature range 104 K to 1010 K at low (0–10 atm) and high pressures (104–108 atm). We investigate the behaviour of partition function and thermodynamic parameters graphically with pressure and temperature. We discuss the effect of high temperature and reduction of confinement radius on these parameters. The present study will be useful in Industrial applications like development of hydrogen fuel and in various physics branches such as in fusion and astrophysical plasma, condensed matter, statistical mechanics and also in other research areas where we encounter atoms which are subjected to high pressures

“Stop the ticking before it blows:” treatment modalities of peri-implantitis

The serendipitous discovery of osseointegration and the subsequent development of dental implants have irrefutably marked an epoch-making point of inflection in not only the basic approach of the clinicians toward treating edentulism but also in the attitudes and preferences of the patients in getting their oral rehabilitation issues resolved. This decisive shift also triggered explosive research targeting improvement in various aspects of dental implants. However, initial success in osseointegration does not necessarily translate into success in long-term function. A successfully osseointegrated implant may be afflicted with early or late complications in due course of service. Of these, peri-implantitis (PI) is considered one of the most common causes of implant failure. For the treatment of peri-implant diseases (mucositis and PI), various conservative and surgical approaches are available. Mucositis and moderate forms of PI can be contained effectively using conservative methods. These include the administration of systemic and local antibiotics alone or in conjunction with other treatment modalities such as nonsurgical therapy which consists of mechanical debridement of the affected areas, irrigation with antiseptics (such as chlorhexidine, saline, and 10% hydrogen peroxide) with or without surface decontamination, laser-supported therapy, photodynamic therapy as well as light-activated disinfection also known as photodynamic antimicrobial chemotherapy along with maintaining adequate plaque control. In cases with advanced PI, surgical therapies are more effective than conservative approaches. Open flap debridement can be done, and depending on the configuration of the defect, regenerative therapies such as guided tissue regenerative and the use of bone graft materials may be applicable for defect filling whereas resective surgery can be considered for the elimination of peri-implant lesions

A study on cervical screening by PAP smear and correlation with microbiological and clinical finding

Introduction: Cervical cancer is one of the most common cause in India with over 75% of incidence and mortality. The objective of cervical cancer screening, therefore, is the detection of these lesions before developing into invasive cervical cancer.Methods: This prospective study was carried out over 2 year at the Department of Obstetrics and Gynaecology in National Institute of Ayurveda, Jaipur. Pap smears were collected from 400 sexually active women who were more than 21 years of age.Result: Most common findings were Inflammatory lesion (46.5%), followed by NILM(30%). Atrophic smear was seen in 16 cases (4%), rest had abnormal cellular changes in the form of ASCUS (1.25 %), LSIL (2 %) and Carcinoma (1%).Conclusion : Inflammatory smear is most common cytological finding in premenopausal age group . Epithelial cell abnormality is most common finding in premenopausal and postmenopausal age groups. Pap smear examination can be coupled with culture and sensitivity of vaginal swab to provide adequate treatment

Polyaniline Chromium Nitrate Composites: Influence of Chromium Nitrate on Conductivity and Thermal Stability of Polyaniline

198-205Thermal stability and electrical conductivity are the key to the technological feasibility and sustainability of conducting polymers (CPs) and their composites in real-time applications. Notably, the impact of filler loading on above mentioned parameters of CPs needs to be examined and addressed with facile and easily accessible techniques. In the present study, Polyaniline (PANI) /chromium nitrate composites have been prepared via in situ polymerization of aniline through the chemical oxidative polymerization route. After that, the conductivity and thermal stability of PANI have been investigated at different weight percentage loadings of chromium nitrate viz 5, 10, 20, and 40 % in the composite materials. The morphological and structural analysis of the pristine and composite samples were executed with Scanning electron microscopy (SEM), Fourier transforms infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) techniques. Thermal analysis of proposed composites is carried out using the thermogravimetric analysis (TGA) method to evaluate various kinetic parameters. The TGA thermogram and different calculated parameters revealed that the composites were more thermally stable than pristine PANI and that the composite having 20 wt % of chromium nitrate is thermally the most stable. The DC electrical conductivity data shows that PANI loaded with 20% chromium nitrate has the highest conductivity. This increment in conductivity and thermal stability of the composites opens the path for many applications, such as sensors and electronics

Infigratinib in patients with advanced cholangiocarcinoma with gene fusions/translocations: the PROOF 301 trial.

Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain alterations. Infigratinib is an oral FGFR 1-3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic -altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 (ClincalTrials.gov)