352 research outputs found
Synthesis of New Series of Pyrazoline, and Study their Kinetics and Reaction Mechanism
A new series of novel pyrazoline compounds were synthesized by addition of thiosemicarbazide to the 2,6-dibenzylidenecyclohexanone (Chalcone) and its para substituted derivatives. This study was conducted for four purposes. Firstly, a series of five membered ring pyrazoline compounds were synthesized and the structure of all new products obtained are supported by spectral data (1H-NMR, 13CNMR, IR and UV-Vis.), and the effect of substituents were studied. Secondly, the reaction kinetics of the new synthesized compounds were studied to investigate the reaction mechanism pathway and order of the reaction; it was found that, the reaction undergoes via Claisen route of mechanism with first-order reaction. Thirdly, the thermodynamics of the reaction were studied, the rate of the reaction, Arrhenius parameters (A), and thermodynamic parameters for activation includes (free energies (Ea), entropies (ΔS#), and Gibbs free energy (ΔG#) were estimated. Finally, the compensation effect was also studied, and found the same pathway for all of the synthesized pyrazoline compounds
Heating up the cold bounce
Self-dual string cosmological models provide an effective example of bouncing
solutions where a phase of accelerated contraction smoothly evolves into an
epoch of decelerated Friedmann--Robertson--Walker expansion dominated by the
dilaton. While the transition to the expanding regime occurs at sub-Planckian
curvature scales, the Universe emerging after the bounce is cold, with sharply
growing gauge coupling. However, since massless gauge bosons (as well as other
massless fields) are super-adiabatically amplified, the energy density of the
maximally amplified modes re-entering the horizon after the bounce can
efficiently heat the Universe. As a consequence the gauge coupling reaches a
constant value, which can still be perturbative.Comment: 28 pages, 13 figure
Patient preferences for topical treatment of actinic keratoses:a discrete-choice experiment
Funding: This study was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit programme (PB-PG-0110-21244), Department of Health, UK. The funder was not involved in the study design. Acknowledgments: The authors gratefully acknowledge support from the Cancer Research UK Clinical Trials Unit, the UK Dermatology Clinical Trials Network, the NIHR Clinical Studies Group, and support for investigators from the British Skin Foundation and Cancer Research UK. We would also like to thank Martin Jones, Daniel Rigby and Ariel Bergmann for constructive comments on the design of the DCE.Peer reviewedPostprin
High-throughput small molecule screen identifies inhibitors of aberrant chromatin accessibility
Transcriptional regulators lacking enzymatic activity or binding pockets with targetable molecular features have typically been considered “undruggable,” and a reductionist approach based on identification of their molecular targets has largely failed. We have demonstrated that the Ewing sarcoma chimeric transcription factor, EWSR1-FLI1, maintains accessible chromatin at disease-specific regions. We adapted formaldehyde-assisted isolation of regulatory elements (FAIRE), an assay for accessible chromatin, to screen an epigenetically targeted small molecule library for compounds that reverse the disease-associated signature. This approach can be applied broadly for discovery of chromatin-based developmental therapeutics and offers significant advantages because it does not require the selection of a single molecular target. Using this approach, we identified a specific class of compounds with therapeutic potential
Evaluation of the efficacy, safety and tolerability of Tacrolimus ointment in Indian patients of moderate to severe atopic dermatitis: A multicentric, open label, phase III study
AIM OF STUDY: Tacrolimus, a topical immunomodulator, has been
introduced as a new treatment for moderate to severe atopic dermatitis.
The present study was conducted to evaluate the efficacy, safety and
tolerability of Tacrolimus ointment in patients of atopic dermatitis in
an Indian setting. METHODS: The present study was a prospective, open,
multicentric, Phase III trial.The duration of study was 5 weeks,
including a 3-week active treatment period, preceded by a 1-week
washout phase and followed by a 1-week follow-up phase. Patients
diagnosed to be suffering from moderate to severe atopic dermatitis as
per the Rajka and Langeland criteria were treated with Tacrolimus
ointment 0.03% twice daily. Efficacy was assessed by modified Eczema
Area Sensitivity Index (mEASI) score, patient's and physician's global
assessment. Tolerability and safety was assessed by physical
examination, laboratory parameters and evaluation of adverse events.
RESULTS: There was a statistically significant decrease in the modified
Eczema Area Sensitivity Index (mEASI) score (P<0.05). Patient's and
Physician's global evaluation of treatment was complete resolution to
very good improvement in most of the patients. The laboratory values
were within normal limits. The drug was well tolerated. CONCLUSIONS:
This study confirms the efficacy and safety of Tacrolimus ointment
0.03% in Indian patients of moderate to severe atopic dermatitis
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The relationship between stimulus intensity and response amplitude for the photopic negative response of the flash electroretinogram
The aim of this study was to investigate the relationship between stimulus intensity and response amplitude for the photopic negative response (PhNR) of the flash ERG. Specific aims were (i) to determine whether a generalized Naka-Rushton function provided a good fit to the intensity-response data and (ii) to determine the variability of the parameters of the best-fitting Naka-Rushton models. Electroretinograms were recorded in 18 participants, on two occasions, using both DTL fibre and skin active electrodes, in response to Ganzfeld red stimuli (Lee filter "terry red") ranging in stimulus strength from -1.30 to 0.53 log cd.s.m(-2) (0.28-2.11 log phot td.s) presented over a steady blue background (Schott glass filter BG28; 3.9 log scot td). PhNR amplitude was measured from b-wave peak and from pre-stimulus baseline. The Naka-Rushton function was fitted to all intensity-response data, and parameters, 'n', 'Vmax' and 'K' were obtained. Coefficients of variation (CoV), and inter-ocular and inter-session limits of agreement (LoA) were calculated for both Naka-Rushton parameters. A generalized Naka-Rushton function was found to provide a good fit to the intensity-response data, except at the highest stimulus intensity, where a reduction in amplitude occurred in many individuals. The 'Vmax' parameter was less variable than 'K' for all intensity-response data. Variability was lower for DTL than skin electrodes, and for peak-to-trough PhNR measurements, compared to baseline-to-trough. This study has demonstrated for the first time that the Naka-Rushton model provides a useful means of quantifying the intensity-response relationship of the PhNR
Einstein's quantum theory of the monatomic ideal gas: non-statistical arguments for a new statistics
In this article, we analyze the third of three papers, in which Einstein
presented his quantum theory of the ideal gas of 1924-1925. Although it failed
to attract the attention of Einstein's contemporaries and although also today
very few commentators refer to it, we argue for its significance in the context
of Einstein's quantum researches. It contains an attempt to extend and exhaust
the characterization of the monatomic ideal gas without appealing to
combinatorics. Its ambiguities illustrate Einstein's confusion with his initial
success in extending Bose's results and in realizing the consequences of what
later became to be called Bose-Einstein statistics. We discuss Einstein's
motivation for writing a non-combinatorial paper, partly in response to
criticism by his friend Ehrenfest, and we paraphrase its content. Its arguments
are based on Einstein's belief in the complete analogy between the
thermodynamics of light quanta and of material particles and invoke
considerations of adiabatic transformations as well as of dimensional analysis.
These techniques were well-known to Einstein from earlier work on Wien's
displacement law, Planck's radiation theory, and the specific heat of solids.
We also investigate the possible role of Ehrenfest in the gestation of the
theory.Comment: 57 pp
A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis
The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF), a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity
Topical Polyethylene Glycol as a Novel Chemopreventive Agent for Oral Cancer via Targeting of Epidermal Growth Factor Response
Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG) has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide) rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall) post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat) without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells) and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis
Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design
Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions
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