Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters.

Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle

Multipartite minimum uncertainty products

In our previous work we have found a lower bound for the multipartite uncertainty product of the position and momentum observables over all separable states. In this work we are trying to minimize this uncertainty product over a broader class of states to find the fundamental limits imposed by nature on the observable quantites. We show that it is necessary to consider pure states only and find the infimum of the uncertainty product over a special class of pure states (states with spherically symmetric wave functions). It is shown that this infimum is not attained. We also explicitly construct a parametrized family of states that approaches the infimum by varying the parameter. Since the constructed states beat the lower bound for separable states, they are entangled. We thus show that there is a gap that separates the values of a simple measurable quantity for separable states from entangled ones and we also try to find the size of this gap.Comment: 18 pages, 5 figure

Učinkovitost i kvaliteta indukcijskog zagrijavanja i kaljenja osovina startera dizel motora

Presented work discusses a complex process of inductive heating and quenching of carbon steel planetary shafts for diesel engine starters. On the measurements base of temperature fields on the surface of the planetary shafts by thermographic camera and theoretical knowledge, a mathematical model for temperature conditions determination in the shaft during the entire process of heating and quenching was carried out. On the basis of developed mathematical model a computer program was developed, and used for analyses and induction hardening process optimization of planetary shafts.U ovom se radu raspravlja o složenom procesu indukcijskog zagrijavanja i kaljenja osovina iz ugljičnog čelika za pokretanje dizelskih motora. Na temelju rezultata mjerenja temperaturnih polja na površini osovina termografskom kamerom i teorijskih spoznaja, razvijen je matematički model temperaturnih uvjeta tijekom procesa zagrijavanja i kaljenja osovina. Na temelju postavljenog matematičkog modela razvijen je računalni program koji je korišten za analizu i optimizaciju procesa zagrijavanja osovina

The Croatian Health Survey – SF-36: I. General Quality of Life Assessment

The objective of the Croatian Health Survey was the assessment of population health related quality of life in the transitional enviroment of Croatia. Health status measures incorporate dimensions such as physical, psychological, and social functioning, role performance and perception of wellbeing. In order to assess health status, »The medical outcome study 36-item short-form health survey (SF-36) model« was used. A total sample of 5048 inhabitants (1983 males and 3065 females), 18 years and over, represents approximately 1‰ of the general population of Croatia. Mean scores were as follows: physical functioning (PF) 69.94, role-physical (RP)63.01, bodily pain (BP) 64.51, general health (GH) 53.40, vitality (VT) 51.85, social functioning (SF) 72.96, role-emotional (RE) 72.42, mental health (MH) 61.71 and health transition (HT) 44.79. Results of the SF-36 health survey in Croatia are very much like the results in other European countries with indication that general quality of life is lower in Croatia

Development of banded microstructure in 34CrNiMo6 steel

In this paper the development of a banded microstructure in hot-rolled 34CrNiMo6 steel which consisted of bainitic and martensitic bands is explained. The chemical compositions of the bands were measured with energy dispersive x-ray spectroscopy (EDS), which showed that the martensitic bands contained more alloying elements (Mn, Cr, Mo, Si) than bainitic bands. By using Oberhoffer reagent, the segregations of phosphorus were also revealed. These phosphorus segregations coincided with the positive segregations of the alloying elements. The continuous cooling transformation (CCT) diagrams of steel were calculated. They confirmed the formation of martensite in positive segregations and the formation of bainite in negative segregations

Artificial neural network modeling and simulation of in-vitro nanoparticle-cell interactions

In this research a prediction model for the cellular uptake efficiency of nanoparticles (NPs), which is the rate that NPs adhere to a cell surface or enter a cell, is investigated via an artificial neural network (ANN) method. An appropriate mathematical model for the prediction of the cellular uptake rate of NPs will significantly reduce the number of time-consuming experiments to determine which of the thousands of possible variables have an impact on NP uptake rate. Moreover, this study constitutes a basis for targeted drug delivery and cell-level detection, treatment and diagnosis of existing pathologies through simulating NP-cell interactions. Accordingly, this study will accelerate nanomedicine research. Our research focuses on building a proper ANN model based on a multilayered feed-forward back-propagation algorithm that depends on NP type, size, surface charge, concentration and time for prediction of cellular uptake efficiency. The NP types for in-vitro NP-healthy cell interaction analysis are polymethyl methacrylate (PMMA), silica and polylactic acid (PLA), all of whose shapes are spheres. The proposed ANN model has been developed on MATLAB Programming Language by optimizing a number of hidden layers (HLs), node numbers and training functions. The datasets are obtained from in-vitro NP-cell interaction experiments conducted by Nanomedicine and Advanced Technology Research Center. The dispersion characteristics and cell interactions with different NPs in organisms are explored using an optimal ANN prediction model. Simulating the possible interactions of targeted NPs with cells via an ANN model will be faster and cheaper compared to the excessive experimentation currently necessary. Copyright © 2014 American Scientific Publishers All rights reserved

Analysis of the in vitro nanoparticle–cell interactions via a smoothing-splines mixed-effects model

A mixed-effects statistical model has been developed to understand the nanoparticle (NP)–cell interactions and predict the rate of cellular uptake of NPs. NP–cell interactions are crucial for targeted drug delivery systems, cell-level diagnosis, and cancer treatment. The cellular uptake of NPs depends on the size, charge, chemical structure, and concentration of NPs, and the incubation time. The vast number of combinations of these variable values disallows a comprehensive experimental study of NP–cell interactions. A mathematical model can, however, generalize the findings from a limited number of carefully designed experiments and can be used for the simulation of NP uptake rates, to design, plan, and compare alternative treatment options. We propose a mathematical model based on the data obtained from in vitro interactions of NP–healthy cells, through experiments conducted at the Nanomedicine and Advanced Technologies Research Center in Turkey. The proposed model predicts the cellular uptake rate of silica, polymethyl methacrylate, and polylactic acid NPs, given the incubation time, size, charge and concentration of NPs. This study implements the mixed-model methodology in the field of nanomedicine for the first time, and is the first mathematical model that predicts the rate of cellular uptake of NPs based on sound statistical principles. Our model provides a cost-effective tool for researchers developing targeted drug delivery systems. © 2015 Informa Healthcare USA, Inc

Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives

Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC