Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain.

The human DNA repair protein MED1 (also known as MBD4) was isolated as an interactor of the mismatch repair protein MLH1 in a yeast two-hybrid screening. MED1 has a tripartite structure with an N-terminal 5-methylcytosine binding domain (MBD), a central region, and a C-terminal catalytic domain with homology to bacterial DNA damage-specific glycosylases/lyases. Indeed, MED1 acts as a mismatch-specific DNA N-glycosylase active on thymine, uracil, and 5-fluorouracil paired with guanine. The glycosylase activity of MED1 preferentially targets G:T mismatches in the context of CpG sites; this indicates that MED1 is involved in the repair of deaminated 5-methylcytosine. Interestingly, frameshift mutations of the MED1 gene have been reported in human colorectal, endometrial, and pancreatic cancers. For its putative role in maintaining genomic fidelity at CpG sites, it is important to characterize the biochemical properties and the substrate spectrum of MED1. Here we show that MED1 works under a wide range of temperature and pH, and has a limited optimum range of ionic strength. MED1 has a weak glycosylase activity on the mutagenic adduct 3,N(4)-ethenocytosine, a metabolite of vinyl chloride and ethyl carbamate. The differences in glycosylase activity on G:U and G:T substrates are not related to differences in substrate binding and likely result from intrinsic differences in the chemical step. Finally, the isolated catalytic domain of MED1 retains the preference for G:T and G:U substrates in the context of methylated or unmethylated CpG sites. This suggests that the catalytic domain is fundamental, and the 5-methylcytosine binding domain dispensable, in determining the substrate spectrum of MED1.
Transradial Versus Transfemoral Carotid Artery Stenting: A 16-Year Single-Center Experience.

AIMS Limited data exist on radial access in carotid artery stenting (CAS). This single-center study was performed to compare the outcome and complication rates of transradial (TR) and transfemoral (TF) CAS. METHODS AND RESULTS The clinical and angiographic data of 775 consecutive patients with high risk for carotid endarterectomy, treated between 1999 and 2016 by CAS with cerebral protection, were evaluated. Patients were divided into 2 groups according to vascular access: TR (n = 101; 13%) and TF (n = 674). Primary combined end-point: in-hospital major adverse cardiac and cerebral events. Secondary end-points: angiographic outcome of the procedure and crossover rate to another puncture site. Angiographic success was achieved in all 775 patients, the crossover rate was 4.9% in the TR and 0% in the TF group (P < 0.05). TR was performed at the right side in 97% of cases. The incidence of in-hospital major adverse cardiac and cerebral events was 2% in the TR and 3.6% in the TF group (P = ns). CONCLUSIONS The TR approach for CAS is safe and efficacious, with acceptable cross-over rate. In both groups, vascular complications rarely occurred.
Constructing racism in Australia

There is a dearth of empirical evidence on the extent of racist attitudes, broadly defined, in Australia. A telephone survey of 5056 residents in Queensland and NSW examined attitudes to cultural difference, perceptions of the extent of racism, tolerance of specific groups, ideology of nation, perceptions of Anglo-Celtic cultural privilege, and belief in racialism, racial separatism and racial hierarchy. The research was conducted within a social constructivist understanding of racisms. Racist attitudes are positively associated with age, non-tertiary education, and to a slightly lesser extent with those who do not speak a language other than English, the Australia-born, and with males. Anti-Muslim sentiment is very strong, but there is also a persistence of some intolerance against Asian, Indigenous and Jewish Australians. Those who believe in racial hierarchy and separatism (old racisms) are a minority and are largely the same people who self-identify as being prejudiced. The 'new racisms' of cultural intolerance, denial of Anglo-privilege and narrow constructions of nation have a much stronger hold. Nonetheless, sociobiologically related understandings of race and nation remain linked to these new racisms. Narrow understandings of what constitutes a nation (and a community) are in tension with equally widely held liberal dispositions towards cultural diversity and dynamism. Encouragingly, most respondents recognise racism as a problem in Australian society and this is a solid basis for anti-racism initiatives.
Dimensions of sexual orientation and HIV-related risk among adolescent females: evidence from a statewide survey.

OBJECTIVES We examined the relationship of 2 dimensions of sexual orientation--sexual identity and sex of partners--with self-reported behaviors and experiences to identify factors that may place adolescent females at risk of HIV/AIDS. METHODS We gathered data on sexually experienced female high school students from 4 waves of a population-based survey. We used logistic regression analyses to investigate the association between their sexual identity (3666 heterosexual; 184 lesbian, gay, or bisexual; 113 not sure) and sex of partners (3714 male only, 79 female only, and 180 both males and females) with HIV-related risk behaviors. RESULTS Self-defined sexual identity was often inconsistent with sex of sexual partners. Sexual identities other than heterosexual and having same-sex partners (either exclusively or in addition to male partners) were associated with high rates of several HIV-related risk behaviors. Coerced sexual contact was significantly associated with every risk outcome. AIDS education in school predicted lower HIV risk on 4 of 6 indicators. CONCLUSIONS Programs to prevent HIV infection among adolescent females should take into account the complexity of sexual orientation and should address the needs and behaviors of sexual-minority youths.
Oxidative stress induced by 2,4‐phenoxyacetic acid in liver of female rats and their progeny: Biochemical and histopathological studies

The 2,4‐Dichlorophenoxyacetic acid (2,4‐D) was used in agriculture as an herbicide in many countries including Tunisia. The aim of this study was to evaluate the effects of 2,4‐D on liver function of adult rats and their progeny. Female Wistar rats were divided into two groups: the controls and the treated rats which received 600 ppm of 2,4‐D in their drinking water from the 14th day of pregnancy until day 14 after delivery. In 2,4‐D group, a significant decrease in body weight of pups was noted, when compared to controls. Liver antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) decreased, while malondialdehyde (MDA) levels increased in dams and pups. Moreover, plasma aminotransferases (ALT, AST), gamma glutamil transpeptidase (GGT), lactate dehydrogenase (LDH), bilirubin and albumin levels were increased significantly. The biochemical modifications were correlated with histopathological studies. We concluded that 2,4‐D induced hepatotoxicity in adult and suckling rats. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Immediate effects of nerve sliders and nerve massage on vibration and thermal perception thresholds in patients with painful diabetic peripheral neuropathy-a pilot randomized clinical trial ( UTRN 103229513-050820102510203 )

Background and purpose: Mechanosensitivity of peripheral nerves was earlier demonstrated in animal models and in experimental human models of diabetic neuropathy and also in asymptomatic human subjects. The purpose of this study was to assess the immediate effects of nerve sliders and nerve massage on vibration perception thresholds (VPT), heat perception thresholds (HPT) and cooling perception thresholds (CPT) in patients with painful diabetic peripheral neuropathy. ,Materials and methods: The study was an observer-blinded pilot randomized sham-controlled clinical trial with concealed allocation on 34 patients (22 male, 12 female) of mean age 53.86 ± 9.85 years with type-2 diabetes mellitus, neuropathic pain for more than one-year, VPT > 25 volts in feet and positive lower extremity neurodynamic testing in bilateral lower limbs suggestive of distal symmetric type of diabetic neuropathy. The tester administered nerve sliders and nerve massage to one lower limb while sham intervention of passive joint movements was performed for the other limb. The choice of first limb was chosen randomly and block randomization was performed to minimize between-side confounding differences. The three outcomes of VPT, HPT and CPT were assessed pre, immediate post and 15 min-post intervention on both feet using a biothesiometer. , Data analysis and results: The data was analyzed using repeated measures analysis of variance at 95% confidence interval using SPSS 12.0. 1 for Windows. Secondary analysis was done using independent t-test for gender and choice of first side. The experimental side had a greater reduction of VPT (12.40 ± 4.90 volts), HPT (7.63 ± 5.18 degree Celsius) and CPT (8.02 ± 5.97 degree Celsius) from pre-treatment to 15min post-treatment compared to the sham side (p<.05). The changes between immediate post-treatment and 15min post-treatment was not significant (p>.05) for all three measurements. , Conclusion: Neurodynamic mobilization comprising of nerve sliders and nerve massage was effective on short-term in reducing VPT, HPT and CPT in patients with painful diabetic peripheral neuropathy compared to a sham intervention. These immediate effects were maintained at 15 min post-treatment.
Agile project management framework

Our article is related to improvement of the product design project management by using some knowledge transferred from the branch of software engineering. We introduce the Agile Project Management Framework – a modern agile framework covering the whole life cycle of project. Especially we describe the phase one of this project framework in more detail. Alongside, we make a mention of using ICT (Information and Communication Technology) and KM (Knowledge Management) tools. Our aim is to define, clearly and logically, the particular phases and stages of project management process in the frame of the whole product life cycle. The result of our work is a detailed referential description of and user guides for the product design project management process based on the agile project management paradigm. The results of our endeavour will be applied in our university courses of the product design project management provided by the department of e-Technology at CTU FEE in Prague.
RELATIONSHIP OF RADIUS TO PRESSURE ALONG THE AORTA IN LIVING DOGS.

The instantaneous pressure-radius relationship and mean dimensions were studied at various sites along the aorta in 30 dogs. The pressure-radius relationship was studied in the living state using an electrical caliper to measure the radius continuously through the cardiac cycle. The relative dimensions of the aortic tree at branching sites were calculated from Jeltrate casts made immediately post mortem. The results indicate: 1 ) The value of ΔR/ΔP and the mean radius decreased with distance along the aorta. 2 ) The calculated value for Ep, the “pressure-strain elastic modulus” increased monotonically from the ascending aorta to the bifurcation. 3 ) An “average” arterial tree was constructed from the mean values of the radius obtained from the caliper data and the branching ratios obtained from the casts. elastic properties, aorta; dimensions, dog aorta Submitted on March 5, 1963
Rabies in Poland in 2009 and 2010

Rabies as a disease still represents a threat to humans and animals, and as zoonosis has to be reported and subjected to official control. Under the current law, dogs over three months old should be compulsory vaccinated and boostered every 12 months. The introduction of the rules reduced significantly the incidence of the disease in these animals (9). However, rabies virus has found a new effective host, and from the middle of the 50’s the red fox has become the main infected species (5). Systematic increase in the number of rabies cases in foxes in 1970’s and the lack of effectiveness of conventional methods of fox rabies control forced the course of action aiming at the disruption of the natural route of disease transmission by reducing the fox population density below a certain threshold, until oral rabies vaccination (ORV) of foxes against rabies has been introduced. ORV was carried out for the first time in 1993 in a limited area of Western Poland and in 2002 the whole area of the country was covered with vaccination. With the enlargement of the area of ORV campaign, the number of rabies cases decreased systematically in subsequent years (4, 6, 7). However, achieving total eradication of rabies, using ORV was more complicated than originally expected. One of the crucial elements of ORV is analysis of the current rabies epidemiological situation on the territory of vaccine distribution. Based on epidemiological analysis correction/modification of ORV campaigns can be made. The objective of this study was to describe and analyse epidemiological data regarding rabies incidence and recent trends of rabies in domestic and wild animals in Poland in 2009 and 2010 with visualisation of geographical distribution of rabies outbreaks.
Antiproliferative effect of an analog of curcumin bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione in human breast cancer cells.

BACKGROUND AND OBJECTIVES Curcumin exhibits growth-suppressive activity against a variety of cancer cells, but low bioavailability prevents its use in chemotherapeutic applications. One strategy for circumventing this problem has been the creation of synthetic analogs. In this study we synthesized an analog of curcumin bis-1,7-2(hydroxyphenil)-hepta-1,6diene-3,5diore (BDMC-A) and investigated its anti-breast cancer property. MATERIALS AND METHODS We compared the impact of bis-1,7-2(hydroxyphenil)-hepta-1,6diene-3,5diore (BDMC-A) with that of curcumin in human breast cancer cell line MCF-7. MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] cell viability assay was used to examine the cell viability/proliferation. LDH assay and cell counts were performed to assess the cytotoxicity and anti-proliferative effects of the compound respectively. Flow cytometry followed by Western blot were performed to investigate the cell cycle distribution. RESULTS BDMC-A has an inhibitory effect on MCF-7 cells comparably equivalent to that of curcumin as determined by MTT assay. Cytotoxicity of the cells by both curcumin and BDMC-A were confirmed by LDH release assay and cell count assay. Flow cytometric studies showed accumulation of cells in the G2/M phase which confirms the cell cycle arrest. This was further confirmed by immunoblotting of the protein Cyclin D1, whose expression were found to be decreased in both curcumin and BDMC-A treatment. CONCLUSIONS The results indicate that the curcumin analog exhibit potent inhibitory activity which is comparable to that of curcumin in human breast cancer cells. Since the solubility of BDMC-A was higher in aqueous medium, it is expected to be more bioavailable, and hence more active in vivo. Further evaluation might reveal its role on various molecular targets.
Determination of Ulifloxacin by Terbium-sensitized Fluorescence with Second-order Scattering and Its Applications

This paper reports the determination of ulifloxacin (UFX) by terbium-sensitized fluorescence using a second-order scattering method. UFX and Tb(III) ion form a fluorescence complex in aqueous solution, and its maximum excitation and emission wavelengths are located at 273 and 545 nm, respectively. In optimum conditions, the relative intensity at 545 nm has a linear relationship to the concentration of UFX in the range of 2.0 × 10^-8 - 1.0 × 10^-5 mol L^-1 and the detection limit is 3.9 × 10^-9 mol L^-1. The proposed method was applied to the determination of UFX in spiked human serum and urine satisfactorily. The luminescence property of UFX is also discussed by comparing with norfloxacin (NFLX) and ofloxacin (OFLX).
Cadmium induces reactive oxygen species-dependent apoptosis in MCF-7 human breast cancer cell line

Abstract Context and objective: Although low concentrations of cadmium exposure may enhance growth of human cultured cells, high and long term of this heavy metal leads to cell death through apoptosis or necrosis. This study was conducted to define the underlying biochemical mechanism of Cd-induced cell death in MCF-7 human breast cancer cell line. Methods: The MCF-7 breast cancer cells were treated with different concentrations of CdCl2 and cell viability was assessed using the MTT assay. A propidium iodide (PI) and annexin-V staining flow cytometric method was used for apoptosis detection. Hoechst 33342 staining was used to observe the morphological changes of cell apoptosis. The cellular DNA was isolated using DNA kit extraction and analyzed electrophoretically. Intracellular reactive oxygen species (ROS) levels were quantified using the fluorescent dye (DCFH-DA). Results: A progressive loss in cell viability and an increased number of apoptotic cells were observed upon 48 h exposure to CdCl2. N-acetylcysteine (NAC) administration reversed the cadmium cytotoxicity effects and protected cells from apoptotic death. Simultaneously, significant elevations of ROS levels were revealed in a dose-dependent manner during the exposure. Typical morphological changes of apoptosis were observed with Hoechst staining after cadmium treatment. Conclusion: These results suggest that during the apoptosis mediated by cadmium chloride, ROS production and oxidative damage may be an initiating event and responsible for the mechanism of MCF-7 human breast cell death.
Lexical Decision for Inflected Nouns

Lexical decision times were measured for three grammatical cases of inflected Serbo-Croatian nouns. The grammatical cases occur with different frequencies. Decision times were not related by a unique constant multiplier to the logarithms of the respective case frequencies. The result suggests that a principle of organization in addition to frequency of occurrence is involved in the lexical memory of inflected nouns.
Development of microextraction techniques in combination with GC-MS/MS for the determination of mycotoxins and metabolites in human urine.

Simple and highly efficient sample preparation procedures, namely, dispersive liquid-liquid microextraction and salting-out liquid-liquid extraction for the analysis of ten Fusarium mycotoxins and metabolites in human urine were compared. Various parameters affecting extraction efficiency were carefully evaluated. Under optimal extraction conditions, salting-out liquid-liquid extraction showed a better accuracy (84-96%) and precision (<14%) than dispersive liquid-liquid microextraction. Hence, a multibiomarker method based on salting-out liquid-liquid extraction followed by gas chromatography with tandem mass spectrometry was proposed. Satisfactory results in terms of validation were achieved. The method resulted in low limits of detection and quantitation within the range of 0.12-4 and 0.25-8 μg/L, respectively. The method accuracy and precision were evaluated at three spiking levels (8, 25 and 100 μg/L) and the recoveries were in a range from 70 to 120% with relative standard deviations lower than 15%. Matrix effect was evaluated and matrix-matched calibrations were used for quantitation purpose. The developed method was applied in 12 human urine samples as a pilot study before and after sample treatment with β-glucuronidase before the analysis to quantify the mycotoxin conjugates. Total deoxynivalenol (free + conjugated) was found in 83% of samples at an average concentration in positive samples of 31.6 μg/L.
Frequent amyloid deposition without significant cognitive impairment among the elderly.

OBJECTIVE To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. DESIGN Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). SETTING University medical center. PARTICIPANTS From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. MAIN OUTCOME MEASURES Regional PiB retention and cognitive test performance. RESULTS Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. CONCLUSIONS Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.