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Supporting Figures S1â S16. (DOCX 8.22 kb)

Figure S1. Sample size by recruitment centers. (PDF 10 kb)

Figure S3. Correlation heatmap of methylation levels inside the two most significant DMR of folate and alcohol. (PDF 43 kb)

Figure S4. DMRs and FL regions of folate in each chromosome. Dark blue rectangles represent DMRs and light blue FL regions. Overlaps between the two methods are represented by red points. Positive coefficients of the two methods are represented on the top part of each graphic, and negative coefficients are on the bottom part. Positive (negative) coefficients of DMRs were set to 0.5 (− 0.5) and positive (negative) coefficients of FL regions were set to 1 (− 1) to clearly differentiate DMRs from FL regions. The x-axis represents the rank of CpG sites according to their position on the chromosome. (PDF 12 kb)

Figure S2. Graphical representation of the most 2 significant DMR of dietary folate and alcohol intake. The x-axis represents the position (hg 19 coordinates) of the CpGs included in the plotted DMR. Each tertile of dietary folate, alcohol intake, or their interaction is represented by different colors: green for T1, blue for T2, and red for T3. For all the CpGs included in the plotted DMR, the dashed lines are their 1st and 3rd quartiles of methylation levels and the points represent their median values. (PDF 33 kb)

Table S2. DMRs associated with alcohol intake. (DOCX 34 kb)

Figure S5. DMRs and FL regions of alcohol in each chromosome. Dark blue rectangles represent DMRs and light blue FL regions. Overlaps between the two methods are represented by red points. Positive coefficients of the two methods are represented on the top part of each graphic and negative coefficients are on the bottom part. Positive (negative) coefficients of DMRs were set to 0.5 (− 0.5), and positive (negative) coefficients of FL regions were set to 1 (− 1) to clearly differentiate DMRs from FL regions. The x-axis represents the rank of CpG sites according to their position on the chromosome. (PDF 58 kb)

Obrada visokim tlakom podrazumijeva podvrgavanje tekuće ili čvrste hrane, s ambalažom ili bez nje, djelovanju tlaka od 100 do 800 MPa (1200 MPa). Temperatura obrade može se kretati od ispod 0 °C do iznad 100 °C, a vrijeme izloženosti djelovanju tlaka, ovisno o cilju obrade, može varirati od nekoliko sekundi do preko 20 minuta. Zbog djelovanja visokog tlaka dolazi do smanjenja obujma sustava i pospješivanja onih reakcija koje vode smanjenju obujma. Potencijal primjene visokog tlaka u obradi hrane je u inaktivaciji mikroorganizama, modifikaciji funkcionalnih svojstava biopolimera, postizanju funkcionalnosti proizvoda te zadržavanju čimbenika kvalitete (boja, aroma, nutritivni sastav). Komponente odgovorne za specifičnu nutritivnu vrijednost i organoleptičke značajke hrane praktički su neosjetljive na djelovanje tlaka. Cilj rada je, polazeći od teorijskih principa djelovanja visokog tlaka, uzimajući u obzir njegove prednosti i nedostatke, prikazati mogućnosti primjene u postupcima obrade hrane. U radu su također opisani tipovi uređaja za tretiranje visokim tlakom koji se mogu primijeniti u obradi hrane. Osim sposobnosti uništavanja mikroorganizama pri sobnoj temperaturi što ovu tehnologiju čini danas jedinom komercijalno primjenjivom alternativom termičkom tretiranju, u radu su prikazane i specifične mogućnosti primjene visokog tlaka u preradi mlijeka, mesa te voća i povrća. S obzirom na trend rastuće potražnje za hranom bez dodataka koja u velikoj mjeri ima zadržane značajke kvalitete (boja, aroma, nutritivni sastav, tekstura), uz ujedno zajamčenu mikrobiološku stabilnost, može se očekivati da će metoda obrade hrane visokim tlakom u budućnosti naći svoju širu primjenu i to upravo za proizvode koji zahvaljujući svojoj dodanoj vrijednosti imaju istaknuto mjesto na tržištu., In high pressure processing, foods are subjected to pressures generally in the range of 100 – 800 (1200) MPa. The processing temperature during pressure treatments can be adjusted from below 0 °C to above 100 °C, with exposure times ranging from a few seconds to 20 minutes and even longer, depending on process conditions. The effects of high pressure are system volume reduction and acceleration of reactions that lead to volume reduction. The main areas of interest regarding high-pressure processing of food include: inactivation of microorganisms, modification of biopolymers, quality retention (especially in terms of flavour and colour), and changes in product functionality. Food components responsible for the nutritive value and sensory properties of food remain unaffected by high pressure. Based on the theoretical background of high-pressure processing and taking into account its advantages and limitations, this paper aims to show its possible application in food processing. The paper gives an outline of the special equipment used in highpressure processing. Typical high pressure equipment in which pressure can be generated either by direct or indirect compression are presented together with three major types of high pressure food processing: the conventional (batch) system, semicontinuous and continuous systems. In addition to looking at this technology’s ability to inactivate microorganisms at room temperature, which makes it the ultimate alternative to thermal treatments, this paper also explores its application in dairy, meat, fruit and vegetable processing. Here presented are the effects of high-pressure treatment in milk and dairy processing on the inactivation of microorganisms and the modification of milk protein, which has a major impact on rennet coagulation and curd formation properties of treated milk. The possible application of this treatment in controlling cheese manufacture, ripening and safety is discussed. The opportunities for its application within the meat processing sector are also discussed, particularly the specific effects of high pressure on the colour, texture, nutritive value and functional properties of fresh and processed meat. This paper also considers the possibilities of implementing high-pressure technology in fruit and vegetable processing with the aim to maintain microbiological safety, nutritive value, “fresh-like” appearance and antimutagenic properties. The intention of this paper is to broaden the knowledge of experts and technologists regarding implementation possibilities of high pressure, as one of the emerging technologies in the various food-processing sectors. Given the trend of growing consumer preferences for fresh-like, additive-free and microbiologically safe food, high pressure processing is likely to find its future application in food processing for niche products with added value.

Ultrazvuk iskazuje frekvenciju zvuka koja se nalazi između 18 i 100 kHz, što je iznad čujnosti ljudskog uha. Ultrazvuk visoke snage znači primjenu intenziteta višeg od I=1Wcm-2(uobičajeno u rasponu od I=10 - 1000Wcm-2). Ultrazvuk visoke snage i niskih frekvencija (f=20 do 100 kHz) smatra se "snažnim ultrazvukom" jer uzrokuje pojavu kavitacije te ima primjenu u prehrambenoj industriji. Primjenjuje se kod odzračivanja tekuće hrane, za induciranje reakcija oksidacije/redukcije, za ekstrakciju enzima i proteina, za inaktivaciju enzima i za indukciju nukleacije kod kristalizacije. Nadalje, ultrazvuk pospješuje prijenos topline, primjenjuje se kod emulgiranja, sterilizacije, ekstrakcije, odzračivanja, filtriranja, sušenja i pojačavanja oksidacije. Konvencionalno sušenje toplim zrakom je energetski veoma zahtjevno i posljedično zahtijeva veća financijska izdvajanja. Primjene različitih predtretmana kao što su osmotska dehidratacija, ultrazvuk i ultrazvukom potpomognuta osmodehidratacija pokazale su različite učinke na voće i povrće. Prolaskom akustičke energije visokog intenziteta kroz čvrsti medij zvučni val uzrokuje serije brzih i sukcesivnih kompresija i opuštanja s brzinama koje ovise o njegovoj frekvenciji. Zbog toga je materijal izložen brzim serijama promjenjivih stezanja i širenja, vrlo nalik neprekidnom stiskanju i opuštanju spužve. Ovaj mehanizam, poznat kao "rektificirana difuzija", vrlo je važan u akustičkom sušenju i migraciji vlage. Primjena ultrazvuka kao prethodne obrade pokazala je velik utjecaj na skraćivanje kasnijeg trajanja sušenja vrućim zrakom, te samim time i ukupna operacija sušenja. Pokazano je da obrada prije provedbe sušenja omogućava bolji prijelaz mase i difuzivnost vode od osmotske dehidratacije. Kvaliteta proizvoda koji se stavlja na sušenje je veća jer se prethodna obrada ultrazvukom primjenjuje pri sobnoj temperaturi čime se smanjuju nepoželjne promjene na strukturi, senzorskim karakteristikama, te gubitci nutritivnih komponenta voća i povrća., Ultrasound is a sound frequency in the range between 18 and 100 kHz that is above hearing of the human ear. High power ultrasound means application of intensities higher than 1 W cm–2 (usually in the range between I=10–1000Wcm–2). High power and low frequency ultrasound (f = 20 to 100 kHz) is considered as “power ultrasound” because its application causes cavitation and is applied in the food industry. High power ultrasound is applied for degassing of liquid food, for induction of oxidation/reduction reactions, for extraction of enzymes and proteins, for inactivation of enzymes and induction of nucleation for crystallization. Ultrasound is anticipating heat transfer; it is used for emulsifying, sterilization, extraction, degassing, filtrating, drying and induction of oxidation. Conventional hot air drying is a very energy- and cost-intensive process. Drying is a simultaneous operation of heat and mass exchange that is followed by phase changes. Application of different pretreatments, like osmotic dehydration, ultrasound and ultrasound assisted osmotic dehydration has shown different effects on fruits and vegetables. When the high intensity acoustic energy is passing through solid material, it causes several fast and successive compressions and rarefactions with speeds that depend on the frequency applied. Thus, material is exposed to a series of exchangeable squeezing and relaxations, very like continuous squeezing and releasing of the sponge. This mechanism known as "rectified diffusion" is very important in acoustic drying and migration of water. Application of ultrasound as a pretreatment has shown great influence on reducing afterward hot air drying thereby reducing total drying time. It is also shown that pretreatment before drying facilitates better mass transfer and water diffusivity than osmotic dehydration. Quality of the product after drying is better because ultrasound pretreatment is applied at room temperature thus reducing deteriorating alterations and nutritive loss of compounds in fruits and vegetables. In this paper, the basic theory of ultrasound has been described. In the figures, the range of sound by frequency is described, as is the amplitude of ultrasound and its effect on the material also l, the wavelength and attenuation coefficient have been explained. The most common usage of power ultrasound as probe type of high intensity ultrasound set system with piezoelectric transducer have been introduced as a system for ultrasound drying. When the ultrasound wave passes through material the basic effect occurs. It is called cavitation and is divided generally in two types: stable and transient cavitation. Also, when imploding cavitation bubble causes elevated temperatures and pressures several chemical reactions can happen. In the figure one can see the visualisation of sonochemical reactions that occur around the decomposed bubble. Several reactions of decomposition, polymerisations, formation of aggregates, breaking of aggregates, bonding, breaking of bonds, formation of radicals, hydroxyl radicals etc. The main aim of this paper was to introduce the new non-thermal pre-treatment or direct treatment of ultrasound probe, or set of probes in the drying of vegetables and fruits. The basic target of the paper was to improve the knowledge of experts in the food industry and technologists in the chemical and other industries to learn of the possibility of implementing new techniques in their facilities. One can observe the modern scheme of the system for drying of materials with direct contact and also the example of the ultrasound treatment of fruits, water diffusivity in fruit and total processing time of applying ultrasound. The most important thing is to conduct the drying process in the best way to reduce treatment time, and to optimize the system. The most commonly used mathematical models for determination of drying kinetics have been pointed out. The lack of information is about energy input, and the total quality of dried fruits and vegetables and for that purpose in the future several scientific projects need to be conducted to surely claim the benefit of ultrasound accelerated drying of foodstuffs.

It has proved difficult to develop suitable models to study radiation-induced carcinogenesis by using human epithelial cells. However, immortalised human epithelial cell lines have proved useful. Unirradiated cells from the human keratinocyte cell line (HPV-G) and the human embryonic lung cell line (L132) were found to be tumourigenic in T-cell-deficient mice; thus, they are not suitable for transformation studies. Human urothelial cell lines (SV-HUC-1, NT11, BC16) and the human thyroid epithelial cell line (HTori-3) were nontumourigenic. The urothelial cell lines were refractory to radiation-induced carcinogenesis, and only one small tumour was observed in 57 mice that received irradiated cells. Whereas tumours were not produced following irradiation of these urothelial cells, changes in anchorage-independent growth were observed after a single dose of 8 Gy gamma-irradiation but not after 2 or 4 Gy. Irradiation of the human thyroid epithelial cell line (HTori-3) in vitro resulted in tumour formation. Passaging of the cells in vitro before injection did not seem to be critical. Some of the cell lines derived from the primary thyroid tumours exhibited p53 mutations in exons 5, 6, 7, and 8, as detected by single-stranded conformational polymorphism (SSCP) analysis. Thus, the human thyroid epithelial cell line (HTori-3) looks promising as a model for investigating the molecular events in radiation-induced carcinogenesis.

Obrada visokim tlakom podrazumijeva podvrgavanje tekuće ili čvrste hrane, s ambalažom ili bez nje, djelovanju tlaka od 100 do 800 MPa (1200 MPa). Temperatura obrade može se kretati od ispod 0 °C do iznad 100 °C, a vrijeme izloženosti djelovanju tlaka, ovisno o cilju obrade, može varirati od nekoliko sekundi do preko 20 minuta. Zbog djelovanja visokog tlaka dolazi do smanjenja obujma sustava i pospješivanja onih reakcija koje vode smanjenju obujma. Potencijal primjene visokog tlaka u obradi hrane je u inaktivaciji mikroorganizama, modifikaciji funkcionalnih svojstava biopolimera, postizanju funkcionalnosti proizvoda te zadržavanju čimbenika kvalitete (boja, aroma, nutritivni sastav). Komponente odgovorne za specifičnu nutritivnu vrijednost i organoleptičke značajke hrane praktički su neosjetljive na djelovanje tlaka. Cilj rada je, polazeći od teorijskih principa djelovanja visokog tlaka, uzimajući u obzir njegove prednosti i nedostatke, prikazati mogućnosti primjene u postupcima obrade hrane. U radu su također opisani tipovi uređaja za tretiranje visokim tlakom koji se mogu primijeniti u obradi hrane. Osim sposobnosti uništavanja mikroorganizama pri sobnoj temperaturi što ovu tehnologiju čini danas jedinom komercijalno primjenjivom alternativom termičkom tretiranju, u radu su prikazane i specifične mogućnosti primjene visokog tlaka u preradi mlijeka, mesa te voća i povrća. S obzirom na trend rastuće potražnje za hranom bez dodataka koja u velikoj mjeri ima zadržane značajke kvalitete (boja, aroma, nutritivni sastav, tekstura), uz ujedno zajamčenu mikrobiološku stabilnost, može se očekivati da će metoda obrade hrane visokim tlakom u budućnosti naći svoju širu primjenu i to upravo za proizvode koji zahvaljujući svojoj dodanoj vrijednosti imaju istaknuto mjesto na trŢištu.

The term ‘epigenetic’ refers to all heritable changes in gene expression and associated phenotypic traits that are not coded in the DNA sequence itself. Epigenetic inheritance includes DNA methylation, histone modifications, and micro-RNAs, all of which are essential mechanisms that allow the stable propagation of gene activity states from one generation of cells to the next. Many epidemiological and laboratory-based studies either confirm or implicate epigenetic changes induced by environmental, nutritional, and lifestyle factors in a variety of human cancer. Environmental factors known to play important roles in the etiology of human cancer include chemical carcinogens, such as those found in cigarette smoke; dietary contaminants, such as the aflatoxin B1; and physical carcinogen, such as UV radiation. Lifestyles such as smoking, alcohol consumption, excess exposure to sunlight, and fat consumption are environmental factors that contribute to human malignancies. Epigenetic mechanisms play a critical role in normal physiological responses to environmental stimuli that establish an appropriate gene expression pattern by altering the epigenetic state of the genome. Exposure to environmental, physical, and chemical carcinogens, infectious agents, and lifestyle may induce epigenetic changes that alter critical cellular processes including silencing of tumor suppressor genes, activation of oncogenes, aberrant cell cycle, defects in DNA repair, and deregulation of cell death, all of which may promote the development of cancer.

Mouse embryo fibroblasts lacking poly(ADP-ribose) polymerase (PARP)-1 express a barely detectable level of wild-type (wt) p53 protein. Doxorubicin at concentrations activating wt p53 in normal mouse embryo fibroblasts failed to induce it in mutant cells. wt p53 was only activated in response to a 10-fold higher doxorubicin dose. Treatment with higher doxorubicin concentrations was cytotoxic for normal but not for PARP-1 -/- cells. The latter was also resistant to other anticancer agents. The increased resistance of mutant cells to drugs resembled a unique phenomenon known as multidrug resistance (MDR). Interestingly, the MDR gene product P-glycoprotein was clearly up-regulated in PARP-1-deficient cells as compared with normal counterparts. Pretreatment with verapamil reversed the MDR phenotype.

Human thyroid carcinomas have been induced following exposure of SV40-immortalized human thyroid epithelial cells in vitro to single doses (0.14 Gy to 1.57 Gy) of 3.26 MeV alpha-particles from a plutonium 238 source. Tumours were detected between 50 and 160 days following subcutaneous transplantation of the irradiated cells in athymic mice. No tumours were observed following transplantation of unirradiated cells. The relative biological effectiveness (RBE) of the alpha-particles, estimated from cell survival curves, was 4.8 at 50% survival and 3.3 at 5% survival. A first estimate of the RBE at peak tumour induction was 3.8. This system provides a means of studying the mechanisms of tumourigenesis in human thyroid epithelial cells induced by ionizing radiations, including tumours induced by single alpha particles such as from environmental natural radon and polonium and artificial plutonium and americium, and those induced by beta- or Auger-emissions from particular iodine isotopes.

It has proved difficult to develop suitable models to study radiation-induced carcinogenesis by using human epithelial cells. However, immortalised human epithelial cell lines have proved useful. Unirradiated cells from the human keratinocyte cell line (HPV-G) and the human embryonic lung cell line (L132) were found to be tumourigenic in T-cell-deficient mice; thus, they are not suitable for transformation studies. Human urothelial cell lines (SV-HUC-1, NT11, BC16) and the human thyroid epithelial cell line (HTori-3) were nontumourigenic. The urothelial cell lines were refractory to radiation-induced carcinogenesis, and only one small tumour was observed in 57 mice that received irradiated cells. Whereas tumours were not produced following irradiation of these urothelial cells, changes in anchorage-independent growth were observed after a single dose of 8 Gy gamma-irradiation but not after 2 or 4 Gy. Irradiation of the human thyroid epithelial cell line (HTori-3) in vitro resulted in tumour formation. Passaging of the cells in vitro before injection did not seem to be critical. Some of the cell lines derived from the primary thyroid tumours exhibited p53 mutations in exons 5, 6, 7, and 8, as detected by single-stranded conformational polymorphism (SSCP) analysis. Thus, the human thyroid epithelial cell line (HTori-3) looks promising as a model for investigating the molecular events in radiation-induced carcinogenesis.

Radiation-induced transformation of a human thyroid epithelial cell line (HTori-3) has been investigated following exposure to single and fractionated doses of gamma-irradiation. The human epithelial cells were irradiated in vitro and following passaging, transplanted to the athymic nude mouse. Following a single exposure to gamma-irradiation in the range 0.5-4 Gy, 22 tumours were observed in 45 recipients and following three equal fractions in the range 0.5-4 Gy per fraction, 18 tumours were observed in 31 recipients. Tumours were undifferentiated carcinomas and were observed from 7 to 20 weeks after transplantation. They occurred after similar radiation doses to those received by the children in the Belarus region of Ukraine, who developed thyroid tumours. The number of tumours observed, in each group receiving cells irradiated with a single dose of gamma-irradiation in the range 0.5-4 Gy, was similar. Cell lines were established from some tumours and the tumorigenicity confirmed by retransplantation. These tumour cell lines were more radiosensitive than the human thyroid epithelial cell line they were derived from. This indicates that transformed cells were not being selected from a subpopulation within the parent cell line but that radiation-induced transformants were being induced de novo. The human origin of the tumours was established by karyotyping, immunocytochemical demonstration of human epithelial cytokeratins and p53 analysis. DNA fingerprinting confirmed that the tumours were derived from the original cell line. Human epithelial cells have proved difficult to transform by exposure to radiation. This human thyroid epithelial cell line can be transformed by single and fractionated doses of gamma-irradiation and promises to be a useful model for studying the mechanisms of radiation-induced transformation of human epithelial cells.

A case report is presented of a man with pronounced tracheobronchomegaly who has had respiratory symptoms since childhood. In spite of numerous medical examinations a disease remains undetected for many years. Authors bring up different standpoints about etiology and the most often accepted hypothesis about the autosomal recessive inheritance. They also point their attention to a small number of diagnosed cases despite high prevalence (0,4-1%) and typical symptoms.

An analytical expression is derived for the electrical transparency of a corona triode with a biased parallel wire grid. This analysis is extended to a square grid by modelling it with an equivalent parallel grid having the same optical transparency. The experimental results obtained with a small corona triode, agree with the theoretical model for the parallel wire grids and the square grid with a large optical transparency. For a square grid with transparency less than 60%, good agreement is obtained by allowing one of the terms in the mathematical model to become an experimentally adjusted constant.

In two female workers (nonsmokers) and in one male worker (a smoker) employed in the same mill with a history of asbestosis, bronchogenic lung carcinoma type adenocarcinoma (women), respectively anaplastic carcinoma (a man) had developed. All the three patients worked in the same area in a spinning-mill. The duration of exposure to asbestos was relatively short (10 to 15 years) in female workers, while the duration of exposure to asbestos was much longer in a male worker (29 years), although it was intermittent. Dyspnea was the main and the only discomfort. In accordance with the International Labour Organization (ILO) classification, a chest radiograph revealed the lesions of s/t 1/2 and s/t 2/1 features. There was also a ventilation deficit (very decreased carbon monoxide diffusing capacity).

Table S1. DMRs associated with dietary folate (log). (DOCX 19 kb)

Herceg Z., Juraga E., Sobota-Salamon B., Režek-Jambrak A. (2012): Inactivation of mesophilic bacteria in milk by means of high intensity ultrasound using response surface methodology. Czech J. Food Sci., 30: 108–117. High-intensity ultrasound was used to investigate the inactivation of microorganisms in raw bovine milk. Raw bovine milk with 4% of milk fat was treated with ultrasonic probe that was 12 mm in diameter and with 20 kHz frequency immerged in milk directly. In the ultrasound treatment, three parameters were varied according to the statistical ex perimental design. The centre composite design was used to design and optimise the experimental parameters: tem perature (20, 40, and 60°C), amplitude (120, 90, and 60 µm), and time (6, 9, and 12 min). All analyses were performed immediately after sonication and after 3 days and 5 days of storage under refrigeration at 4°C. The factors that seem to affect substantially the inactivation of microorganisms in using ultrasound are the amplitude of the ultrasonic waves, the exposure/contact time with the microorganisms, and the temperature of the treatment. The results achieved indicate a significant inactivation of microorganisms under longer periods of the treatment with ultrasonic probe, particularly in combination of higher temperature and amplitude. The output optimal value of total bacteria count was defined by Statgraphics where the lowest bacteria count was 3.688 log CFU/ml for the following specific ultrasound parameters: amplitude 120 μm, treatment time 9.84 min, and temperature 45.34°C.

A corona device with point-to-plane electrode geometry is used to simulate electrical operating conditions in industrial electrostatic precipitators. The particular aspect investigated is the effect of electrode coating by precipitated particulates of high resistivity, and as simulated by layers of porous insulating materials. The typical measured d.c.characteristics and square-wave response of the device are presented and discussed. The corona modes are identified from measurements, and the device performance is represented by a lumped-element circuit model based on a spatial systematisation of corona phenomena into four regions described as the primary-ionisation, accumulation, transport, and secondary-ionisation regions. The lumped parameters of the circuit model are used for a semiquantitative formulation of criteria for typical corona modes and corresponding electrical characteristics. Further, the circuit model is implemented in the design of a simple solid-state analogue, which can simulate the negative-corona characteristics of the device under different operating conditions.