Miracle-dz/UniFAR-FTUs huggingface dataset:
Occupational exposures to high frequency electromagnetic fields in the intermediate range ( >300 Hz–10 MHz)

The aim of this study was to identify work situations with electromagnetic fields of 300 Hz–10 MHz and to characterize the occupational exposure. Work place investigations included descriptions of the work environment and physical measurements. We estimated electric (E) and magnetic (H) fields by spot measurements in air, by logged exposure data, and when possible, we recorded induced currents in limbs. The instruments used were Wandel and Golterman EFA‐3, NARDA 8718, Holaday HI‐3702. The exposure sources comprised five induction furnaces, seven induction heaters, one surface treatment equipment, four units of electronic article surveillance (EAS), and medical devices for surgery and muscle stimulation. The induction furnaces operated at 480 Hz–7 kHz, and the maximum values of logged data varied between 512–2093 V/m (E field) and 10.5–87.3 A/m (H field). The induction heaters (3.8 kHz–1.25 MHz) also showed high maximum exposure values of both E and H fields. Three EAS units, an electromagnetic plate at a library, a luggage control unit, and an antitheft gate, showed E fields reaching 658–1069 V/m. The H fields were comparatively lower, except for the antitheft gate (5 and 7.5 kHz) showing a maximum value of 27.2 A/m (recorded during repair). Induced currents of 5–13 mA were measured for the medical devices. The study improves the basis for an exposure assessment for epidemiological studies of long term effects of exposures to high frequency electromagnetic fields. Bioelectromagnetics 23:568–577, 2002. © 2002 Wiley‐Liss, Inc.
Requirement for the Kinase Activity of Human DNA-Dependent Protein Kinase Catalytic Subunit in DNA Strand Break Rejoining

ABSTRACT The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an enormous, 470-kDa protein serine/threonine kinase that has homology with members of the phosphatidylinositol (PI) 3-kinase superfamily. This protein contributes to the repair of DNA double-strand breaks (DSBs) by assembling broken ends of DNA molecules in combination with the DNA-binding factors Ku70 and Ku80. It may also serve as a molecular scaffold for recruiting DNA repair factors to DNA strand breaks. This study attempts to better define the role of protein kinase activity in the repair of DNA DSBs. We constructed a contiguous 14-kb human DNA-PKcs cDNA and demonstrated that it can complement the DNA DSB repair defects of two mutant cell lines known to be deficient in DNA-PKcs (M059J and V3). We then created deletion and site-directed mutations within the conserved PI 3-kinase domain of the DNA-PKcs gene to test the importance of protein kinase activity for DSB rejoining. These DNA-PKcs mutant constructs are able to express the protein but fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant cells. These results indicate that the protein kinase activity of DNA-PKcs is essential for the rejoining of DNA DSBs in mammalian cells. We have also determined a model structure for the DNA-PKcs kinase domain based on comparisons to the crystallographic structure of a cyclic AMP-dependent protein kinase. This structure gives some insight into which amino acid residues are crucial for the kinase activity in DNA-PKcs.
INVITED REVIEW SERIES: UNRAVELLING THE MANY FACES OF COPD TO OPTIMIZE ITS CARE AND OUTCOMES

COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe–COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.
Quantification of antigen‐reactive T cells by a modified ELISPOT assay based on freshly isolated blood dendritic cells

The enzyme‐linked immunospot (ELISPOT) assay has become a widely employed method for quantification of antigen‐reactive T lymphocytes. In recent years, various types of antigen‐presenting cells (APCs) have been tested as stimulator cells in ELISPOT protocols to achieve a highly sensitive and rapid assay which is not impaired by a marked nonspecific cytokine release. However, the currently available APCs still have disadvantages, such as significant background reactivities, limited sensitivity, and time‐consuming preparation procedures. Recently, we succeeded in defining a novel subpopulation of circulating dendritic cells (DCs) that can easily be prepared from human blood. These M‐DC8+ DCs proved to be very effective in the induction of antigen‐specific T cell responses. In the present study we provide evidence that M‐DC8+ DCs are particularly well suited as APCs for the detection of antigen‐specific CD8+ T cells after challenge with viral or tumor peptides in ELISPOT assays. In addition, protein‐loaded M‐DC8+ DCs proved to be quite efficient in the presentation of MHC class II‐bound peptides, thus allowing the determination of frequencies of antigen‐reactive CD4+ T cells. The use of M‐DC8+ DCs as stimulator cells can improve the ELISPOT assay by combining high sensitivity, rapidity, and low background reactivity. J. Clin. Lab. Anal. 16:30–36, 2002. © 2002 Wiley‐Liss, Inc.
Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging.

BACKGROUND AND PURPOSE Sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of conventional MR imaging in predicting glioma grade are not high. Relative cerebral blood volume (rCBV) measurements derived from perfusion MR imaging and metabolite ratios from proton MR spectroscopy are useful in predicting glioma grade. We evaluated the sensitivity, specificity, PPV, and NPV of perfusion MR imaging and MR spectroscopy compared with conventional MR imaging in grading primary gliomas. METHODS One hundred sixty patients with a primary cerebral glioma underwent conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging, and proton MR spectroscopy. Gliomas were graded as low or high based on conventional MR imaging findings. The rCBV measurements were obtained from regions of maximum perfusion. Metabolite ratios (choline [Cho]/creatine [Cr], Cho/N-acetylaspartate [NAA], and NAA/Cr) were measured at a TE of 144 ms. Tumor grade determined with the three methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading. Sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas were also calculated. RESULTS Sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 72.5%, 65.0%, 86.1%, and 44.1%, respectively. Statistical analysis demonstrated a threshold value of 1.75 for rCBV to provide sensitivity, specificity, PPV, and NPV of 95.0%, 57.5%, 87.0%, and 79.3%, respectively. Threshold values of 1.08 and 1.56 for Cho/Cr and 0.75 and 1.60 for Cho/NAA provided the minimum C2 and C1 errors, respectively, for determining a high-grade glioma. The combination of rCBV, Cho/Cr, and Cho/NAA resulted in sensitivity, specificity, PPV, and NPV of 93.3%, 60.0%, 87.5%, and 75.0%, respectively. Significant differences were noted in the rCBV and Cho/Cr, Cho/NAA, and NAA/Cr ratios between low- and high-grade gliomas (P <.0001,.0121,.001, and.0038, respectively). CONCLUSION The rCBV measurements and metabolite ratios both individually and in combination can increase the sensitivity and PPV when compared with conventional MR imaging alone in determining glioma grade. The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.
Selective estrogen enzyme modulator actions of melatonin in human breast cancer cells

Abstract: Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on estrogen‐dependent mammary tumors. Current knowledge about the mechanisms by which melatonin inhibits the growth of breast cancer cells point to an interaction of melatonin with estrogen‐responsive pathways. The intratumoral production of estrogens in breast carcinoma tissue plays a pivotal role in the proliferation of mammary tumoral cells and its blockade is one of the main objectives of the treatment of breast cancer. The aim of the present work is centered on the study of the role of melatonin in the control of some enzymes involved in the formation and transformation of estrogens in human breast cancer cells. The present study demonstrates that melatonin, at physiologic concentrations, modulates the synthesis and transformation of biologically active estrogens in MCF‐7 cells, through the inhibition of sulfatase (STS) and 17β‐hydroxysteroid dehydrogenase type 1 (17β‐HSD1) activity and expression, enzymes involved in the estradiol formation in breast cancer cells. Physiologic concentrations of melatonin also stimulate the activity and expression of estrogen sulfotransferase (EST), the enzyme responsible for the formation of the biologically inactive estrogen sulfates. The level of EST mRNA steady‐state of cells treated with melatonin was three times higher than that in control cells. These findings which document that melatonin has an inhibitory effect on STS and 17β‐HSD1 and a stimulatory effect on EST, in combination with its previously described antiaromatase effect, can open up new and interesting possibilities in clinical applications of melatonin in breast cancer.
Fibrinolytic activity of human mesothelial cells is counteracted by rapid uptake of tissue-type plasminogen activator.

BACKGROUND Human mesothelial cells (HMCs) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), as well as a specific PA inhibitor, PA inhibitor type 1 (PAI-1). In this study, we investigated whether the fibrinolytic capacity of HMCs is further counterbalanced by rapid uptake of t-PA and u-PA from the medium. METHODS Cultured HMCs were used to study the uptake and degradation of radiolabeled t-PA and u-PA in the absence or presence of an inhibitor of cellular protein degradation, chloroquine, and of specific receptor antagonists. Northern blotting and ligand-blotting techniques were applied to demonstrate the presence of specific receptors for binding of t-PA and u-PA. RESULTS At 37 degreesC, HMCs rapidly internalized and degraded 125I-t-PA and 125I-u-PA, which could be inhibited by an excess of unlabeled t-PA and u-PA, respectively, and by the lysosomotropic agent chloroquine. Northern blot analysis showed the expression of low-density lipoprotein (LDL) receptor-related protein (LRP), very low density lipoprotein (VLDL) receptor, and u-PA receptor. The addition of recombinant 39 kDa receptor-associated protein (RAP; an inhibitor of LRP and VLDL receptor) almost completely blocked the degradation of t-PA and partly that of u-PA. RAP ligand blotting demonstrated predominantly the presence of LRP, suggesting a major role for the LRP in mediating uptake and degradation of t-PA in HMCs. Endocytosis of u-PA occurs via two different pathways. After binding to u-PA receptor, a RAP-inhibitable and a non-RAP-inhibitable route for u-PA degradation was demonstrated. Tumor necrosis factor alpha (TNFalpha) diminished the fibrinolytic activity of HMCs by decreasing t-PA and increasing PAI-1 synthesis. The fall in t-PA levels could be counteracted by inhibiting t-PA degradation by either RAP or chloroquine. Interestingly, chloroquine also quenched the TNFalpha-induced changes in t-PA and PAI-1 mRNA levels. Using TNFalpha mutants and agonistic or blocking monoclonal antibodies specific for the TNF receptors p55 and p75, we found evidence that chloroquine interfered with the activation of the TNF receptor p55 and/or its intracellular signaling route. CONCLUSIONS Receptor-mediated endocytosis plays a crucial role in regulating the fibrinolytic capacity of HMCs by its participation in the degradation of t-PA and u-PA, and in the TNFalpha-induced decrease in t-PA and the increase in PAI-1 expression.
Length of sickness absence from work after minor fractures

Rehabilitation professionals sometimes believe that sickness absence from work is unduly prolonged. This paper examines the implications of factors that influence the timing of return to work, among patients with minor fractures, for the appropriateness of the time at which they should return to work. Data about a consecutive series of 85 employed hospital outpatients with fractures of the wrist, hand or foot bones were collected by means of interviews with the patients and from the orthopaedic case notes. The mean length of sickness absence from work was 3 weeks. Variations were related to the site and severity of the injury. Patients with physically heavy jobs, and patients with a husband or wife at home while they were off work, were off work for longer than average (6 and 5 weeks respectively). 76 per cent of the patients said they returned to work at the right time, and 23 per cent too early. Comparable findings relating to fracture patients, appear not to have been reported in the research literature previously. The patients in the series were away from work longer than advocates of aggressive rehabilitation might consider necessary, although the patients themselves felt they had returned to work at the right time or too early. The development of explicit criteria, based on the nature of the patient's injuries, recovery and job, might enable doctors to give patients more helpful advice about the time at which they should appropriately return to work.
Isoform Patterns of Apolipoprotein E in Diabetes Mellitus

Apolipoproteins in delipidated VLDL preparations from normal, diabetic, and non‐diabetic hyperlipidaemic subjects were analysed by SDS‐polyacrylamide gel electrophoresis, and by isoelectric focusing. On electrophoresis, diabetic VLDL contained more apolipoprotein E (17.3 ± 7.3 (± SD)%, n = 54) than did VLDL from hyperlipidaemic (13.4 ± 4.2%, n = 52; p < 0.005) or normal (12.4 ± 2.6%, n = 29; p < 0.001) subjects. Apolipoprotein E excess was also seen when subgroups were characterized by apolipoprotein E phenotype. In diabetic patients of E3/E3 phenotype, apolipoprotein E was 16.4 ± 6.0% (n = 25), compared with 12.9 ± 2.5% in control subjects (n = 14; p = 0.008). Acidic isoforms were more common in 44 diabetic patients with E3/E3 phenotype; E3, E2, E1, and E1′ as percentage of total E apolipoprotein were 58.3 ± 7.6, 24.5 ± 4.4, 13.7 ± 4.5, and 3.8 ± 4.3% respectively, compared with 63.5 ± 10.4 (p = 0.034), 19.1 ± 5.3 (p < 0.001), 13.7 ± 6.5 (NS), and 3.7 ± 2.1% (NS) in 21 normal subjects. In 31 diabetic patients, of apolipoprotein E3/E3 phenotype, E3, E2, E1 and E1′ were 60.2 ± 7.3, 23.4 ± 9.4, 11.1 ± 4.1, and 5.4 ± 3.7%, respectively, compared with 68.0 ± 7.1 (p < 0.001), 21.9 ± 6.4 (NS), 6.3 ± 3.9 (p < 0.001), and 3.7 ± 2.5 (p < 0.05)% in 32 hyperlipidaemic patients. Diabetic patients of E3/E2 phenotype showed less apolipoprotein E3 than normal or hyperlipidaemic subjects, with a similar trend for apolipoprotein E4 in those of E4/E3 phenotype. Increases in minor apolipoprotein E isoforms imply more post‐translational protein modification in people with diabetes.
Depression and retirement in late middle-aged U.S. workers.

OBJECTIVE To determine whether late middle-aged U.S. workers with depression are at an increased risk for retirement. DATA SOURCE Six biennial waves (1992-2002) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51-61-year-olds and their spouses started in 1992. STUDY DESIGN Workers aged 53-58 years in 1994 were followed every 2 years thereafter, through 2002. Depression was coded as lagged time-dependent variables measuring active depression and severity of depression. The main outcome variable was a transition to retirement which was measured using two distinct definitions to capture different stages in the retirement process: (1) Retirement was defined as a transition out of the labor force in the sample of all labor force participants (N=2,853); (2) In addition a transition out of full time work was used as the retirement definition in the subset of labor force participants who were full time workers (N=2,288). PRINCIPAL FINDINGS In the sample of all labor force participants, the presence of active depression significantly increased the hazard of retirement in both late middle-aged men (adjusted OR: 1.37 [95 percent CI 1.05, 1.80]) and women (adjusted OR: 1.40 [95 percent CI 1.10, 1.78]). For women, subthreshold depression was also a significant predictor of retirement. In the sample of full time workers, the relationship between depression and retirement was considerably weaker for women yet remained strong for men. CONCLUSIONS Depression and depressive symptoms were significantly associated with retirement in late middle-aged U.S. workers. Policymakers must consider the potentially adverse impact of these labor market outcomes when estimating the cost of untreated depression and evaluating the value of interventions to improve the diagnosis and treatment of depression.
Mothers' depressive symptoms and infant negative emotionality in the prediction of child adjustment at age 3: Testing the maternal reactivity and child vulnerability hypotheses

Abstract This study examined individual differences in how mothers' depressive symptoms affect children's early adjustment. It tested whether problematic development among children high in negative emotionality is accentuated by (a) maternal reactivity, the negative reactivity of mothers with depressive symptoms to difficult child characteristics; and (b) child vulnerability, the susceptibility of negatively emotional children to the negative parenting of mothers with depressive symptoms. Based on 1,364 participants from the NICHD Study of Early Child Care, results showed that mothers' depressive symptoms predicted greater risk for adjustment problems at age 3 among children who as infants were high rather than low in negative emotionality. Increased risk was evident for behavior problems, low responsiveness, high separation distress, and low social competence. Mediational tests suggested that increased risk reflected maternal reactivity: the stronger mothers' depressive symptoms, the more they responded with negative parenting to children high in negative emotionality. The proposal that child vulnerability mediates the greater impact of mothers' depressive symptoms on negatively emotional children was verified only for separation distress. The results support the proposal that, when mothers are high in depressive symptoms, aversive characteristics of children and their behavior increasingly influence early adjustment and do so because they elicit negative parent behavior.
Item type, occlusion, and gender differences in mental rotation

Two experiments were conducted to examine the role of item type in mental rotation. In each experiment, participants completed two computerized mental rotation tasks, one with blocks as stimuli and one with human figures as stimuli. The tasks were formatted either as a multiple-choice psychometric test (Experiment 1) or as a same–different type task (Experiment 2). Aside from the expected replication of a decreased effect of occlusion on women's accuracy when processing human figures compared to block figures, it was hypothesized that response times would increase when processing the complex but familiar human figures, compared to the simple but unfamiliar block figures. In Experiment 1, the results relevant to occlusion were replicated. However, the presence of a speed–accuracy trade-off suggested that participants processed human figures faster but less accurately than block figures. In Experiment 2, both men and women performed faster and more accurately when processing occluded human figures than when processing nonoccluded human figures. The effect of item type, its potential link to embodied cognition, and the role of strategy selection on gender differences in mental rotation are discussed.
Détection de l'inclinaison des documents arabes imprimés

Dans cet article, nous presentons une nouvelle methode de detection de l'inclinaison de documents arabes imprimes. La transformee de Hough est utilisee et adaptee en tolerant un angle d'inclinaison de 0° a 180°. Nous avons considere les connaissances a priori de l'ecriture arabe imprimee qui est cursive par nature. En effet, en exploitant des traces stables et homogenes, a savoir les liaisons qui relient les caracteres imprimes, et en les modelisant par le centre de leur boite englobante, notre approche permet une meilleure approximation de l'inclinaison du texte imprime, tout en reduisant le temps de calcul. Des experimentations sur cents documents imprimes et varies montrent des resultats prometteurs avec des temps d'executions tolerables dans le contexte d'applications reelles.