Miracle-dz/UniFAR-FTUs huggingface dataset:
Control of hepatocyte DNA synthesis by intracellular pH and its role in the action of tumor promoters

The mechanisms of tumor promotion in liver by various xenobiotics of diverse structure are not well understood. However, these tumor promoters share the ability to exert growth‐stimulatory effects on hepatocytes. Our laboratory has been utilizing normal rat hepatocytes under defined conditions of primary cultures, to investigate growth‐stimulatory actions of liver tumor promoters. We have shown that most, if not all, of the liver tumor promoters tested stimulate hepatocyte DNA synthesis when added in combination with epidermal growth factor (EGF), insulin, and glucocorticoids. In the present study, we sought evidence for the role of the Na+/H+ antiporter and cytoplasmic alkalinization in the direct growth‐stimulatory actions of tumor promoters on hepatocytes. Hepatocytes cultured under conditions (bicarbonate‐buffered medium) where intracellular pH (pHi) was independent of extracellular pH (pHe), EGF‐ and insulin‐stimulated rates of DNA synthesis were unaffected by modest changes in pHe. However, under conditions (HEPES‐buffered medium) where pHi varied in a linear fashion with pHe, rates of EGF‐ and insulin‐stimulated DNA synthesis were highly dependent on pHe. Similarly, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and α‐hexachlorocyclohexane (HCH)‐stimulated DNA synthesis were pHe‐dependent but were stimulatory over different pHe ranges, suggesting that these promoters may act by distinct mechanisms. Chemicals that are capable of inducing rapid cytoplasmic alkalinization, ammonium chloride (1 and 15 mM) and monensin (0.5 μM), were found to stimulate hepatocyte DNA synthesis. The role of the Na+/H+ antiport in controlling pHi of hepatocytes was demonstrated by artificially acidifying 2′,7′‐bis(carboxyethyl)‐5,6‐carboxyfluorescein acetoxymethyl (BCECF)‐loaded isolated hepatocytes with 20 mM sodium acetate and the use of specific inhibitors. Amiloride and its analogues inhibited pHi recovery from the acid load in a dose dependent manner and the relative potency of these inhibitors paralleled their Ki values for the Na+/H+ antiport. At concentrations that stimulate hepatocyte DNA synthesis, some liver tumor promoters phenobarbital (PB) and HCH, were found to cause a rapid rise pHi in isolated hepatocytes which was sensitive to amiloride and its analogues. Taken together, our data suggest that activation of Na+/H+ antiport activity may be one mechanism whereby some liver tumor promoters stimulate hepatocytes DNA synthesis. This study has implications for the mechanisms of tumor promotion in liver carcinogenesis. © 2003 Wiley‐Liss, Inc.
Antibacterial susceptibility patterns of Porphyromonas gingivalis isolated from chronic periodontitis patients.

OBJECTIVES To test the antimicrobial sensitivity of Porphyromonas gingivalis to a panel of eight orally administrable antibiotics in chronic periodontal diseases and to evaluate factors associated with periodontitis in adult patients. STUDY DESIGN A total of fifty strains of P. gingivalis were isolated from one hundred and twenty adult patients with chronic perio-dontitis. Identification of bacteria was carried out by anaerobic culture and biochemical tests. Selected colonies of P. gingivalis were used to evaluate the antibacterial activities of penicillin, metronidazole, amoxicillin, amoxicillin/clavulanic acid, clindamycin, doxy-cycline, ciprofloxacin and azithromycin. RESULTS Most of the patients were female, age ranging between 40 to 50 years. Majority of the patients frequently had scaling and depths of periodontal pockets in infected teeth were 5-8 mm and most of them had hemorrhage during sampling. Susceptibility testing revealed a sensitivity of 100% of P. gingivalis to azithromycin, doxycycline and amoxicillin/clavulanic acid but lower susceptibilities were found for the rest of antibiotic agents evaluated. CONCLUSIONS Frequent scaling in women aged between 40-50 years had positive correlation with chronic periodontitis. The application of antibiotics in conjuction with mechanical debridation, may reflect in the level of resistance of P. gingivalis in patients with chronic periodontal infections. This could suggest periodical antibiotic susceptibility testing is necessary to determine the efficacy of antimicrobial agents if the perfect curing of chronic periodontal diseases after mechanical debridation is meant. Further clinical studies are required to confirm the in vitro results. The only limitation in this study was identification of bacteria to species rather than subspecies level.
A-contrario approach for outlier detection in GNSS positioning

The localization, that allows to precisely know the orientation and position of a system in the environment, is still challenging in urban environments due to satellite occlusion. This phenomenon reduces the data redundancy and provides bad satellite geometry and reflected signals, called multipaths, that distort the measurements and make them erroneous. The RAIM method, integrated in most GPS receivers, deals with one outlier per instant. This assumption is not longer valid in urban areas where more than one outlier have to be considered. This paper proposes a new approach for the detection and exclusion of the outliers in the GPS pseudo-distance observations. From two assumed models representing the distribution of inconsistent data (naive models), two criteria are proposed to partition the dataset between inliers and outliers. Two algorithms implementing these criteria are presented and evaluated on two datasets respectively acquired in an open environment and in an urban environment. The results are compared with methods classically used for such problems. We show that the proposed outliers detection algorithms improve the estimation of the receiver location and, in the presence of 30% or more outliers, outperform the classical approaches.
Predictors of mortality and morbidity in patients with chronic heart failure.

AIMS We aimed to develop prognostic models for patients with chronic heart failure (CHF). METHODS AND RESULTS We evaluated data from 7599 patients in the CHARM programme with CHF with and without left ventricular systolic dysfunction. Multi-variable Cox regression models were developed using baseline candidate variables to predict all-cause mortality (n=1831 deaths) and the composite of cardiovascular (CV) death and heart failure (HF) hospitalization (n=2460 patients with events). Final models included 21 predictor variables for CV death/HF hospitalization and for death. The three most powerful predictors were older age (beginning >60 years), diabetes, and lower left ventricular ejection fraction (EF) (beginning <45%). Other independent predictors that increased risk included higher NYHA class, cardiomegaly, prior HF hospitalization, male sex, lower body mass index, and lower diastolic blood pressure. The model accurately stratified actual 2-year mortality from 2.5 to 44% for the lowest to highest deciles of predicted risk. CONCLUSION In a large contemporary CHF population, including patients with preserved and decreased left ventricular systolic function, routine clinical variables can discriminate risk regardless of EF. Diabetes was found to be a surprisingly strong independent predictor. These models can stratify risk and help define how patient characteristics relate to clinical course.
Early Afterdepolarizations: Role in Conduction Block, “Prolonged Repolarization‐Dependent Reexcitation,” and Tachyarrhythmias in the Human Heart

Early afterdepolarizations (EAD) have been defined by Cranefield as depolarizing afterpotentials that interrupt or delay normal repolarization of the cardiac action potential. ' EAD, which should be properly differentiated from late afterdepolarizations, can result in triggered activity and sustained rhythms under various circumstances. ^"^ The ionic mechanisms responsible for EAD and LAD, which are being studied, are not fully understood at the present time. In a previous review** we addressed the question of the possible role of LAD in human tachycardias. The studies by Damiano and Rosen^" on the effects of pacing on induction and occurrence of EAD raise the question about a possible role of EAD in clinical arrhythmias. This question can only indirectly be answered at the present time. By comparing results of studies on EAD at the cellular level with observations made during clinical electrophysiological investigations in patients with arrhythmias, one can speculate about some situations in which EAD might be a mechanism of the arrhythmia. As previously stressed, the type of arrhythmia, rate, duration, time of occurrence, etiology, and clinical presentation should be carefully considered when trying to identify electrophysiologic mechanisms of clinical tachycardias and conduction defects. ^
Situational Crime Prevention and Cyber-crime investigation: the Online Pedo-pornography case study

In a society where information represents one of the most valuable assets of business and government, an holistic approach to the management of information systems security is mandatory in order to prevent and detect possible abuse and misuse of information. Facing computer crimes requires to look at aspects related to the technical, formal and informal part of an information system, using theories, methods and techniques lying on different disciplines. Although, the majority of methods and techniques to prevent, detect and investigate computer crimes are best practices based on the experience of IT professionals and practitioners and there is a general lack of theories both used and advocated by academics. We expect to contribute to the literature on computer crime detection, prevention and investigation by introducing a new framework, a formalism and techniques strongly founded on social, psychological and organizational theories. Our assumption is that by focusing on human behavior instead of IT, is possible to better understand computer crimes and to offer substantial insight into the area of IS security
{18F}fluorodeoxyglucose positron emission tomography in refractory complex partial seizures

Positron emission tomography with simultaneous electroencephalographic monitoring was performed with {18F}fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during {18F}fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp‐recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.
[Effects of GLP-1 treatment on protection of B cells in Otsuka Long-Evans Tokushima fatty rats].

OBJECTIVE To investigate the effect of GLP-1 on the blood glucose in type 2 diabetic rats, and its protective effects on the islet B cells. METHODS Thirty rats were divided into three groups: spontaneous type 2 diabetes animal model OLETF rats, GLP-1 [from the twelfth week 56 micro/(kg.d), sc] therapy group and LETO rats as control. In the 14th and 20th weeks, standard OGTT including fast and 2 h-plasma glucose were measured respectively. In the 14th weeks, 3 rats from each group were killed randomly, and the rest of the rats were killed until the 20th week. Immunostaining with the marker of PCNA, TUNEL, and insulin assessed metabolic changes in the islet. Ultrastructure of the B cell was observed with the electronic microscope. RESULTS In the 14th and 20th week, AUC for insulin were higher in treated animals (10.86+/-1.56 vs. 9.07+/-1.28, P<0.01) and (13.00+/-1.50 vs. 10.35+/-0.86, P<0.01), which was paralleled by a decrease in AUC for glucose, (29.93+/-3.15 vs. 34.99+/-4.30, P<0.01) and (38.37+/-3.18 vs. 42.38+/-2.37, P<0.01). Ex vivo immunostaining with the marker of cell proliferation, PCNA, showed that the metabolic changes observed in rats treated with GLP-1 were associated with an increase in cell proliferation of the B cell (48.9+/-39.6 vs. 39.6+/-9.3, P<0.05). TUNEL staining, a marker of cellular apoptosis, indicated a reduction of apoptotic cells within the islet in GLP-1-treated rats (24.8+/-4.2 vs. 30.8+/-5.8, P<0.01). Immunostaining for the insulin showed a significant increase in insulin content in GLP-1-treated animals. GLP-1-treatment ameliorated the ultrastructure of the B cell. CONCLUSION Our findings have provided evidence that the beneficial effects of GLP-1 in OLETF rats are mediated by an increase in islet cell proliferation and a decrease of cellular apoptosis.
The undertreatment of dysthymia.

BACKGROUND Dysthymia is a chronic depressive condition that is quite prevalent. This condition can exact a significant toll on the general health and quality of life in the affected individual. Despite the frequency and consequences of dysthymia, however, the condition is often not diagnosed or treated. We present data on prior treatment from 410 patients with DSM-III-R dysthymia, primary type, early onset without concurrent major depression. METHOD Axis I and II diagnoses were made by using the Structured Clinical Interviews for DSM-III-R, Patient Version (SCID-P) and SCID II for Personality Disorders. The Hamilton Rating Scale for Depression and the Clinical Global Impressions scale were also completed. Prior treatment was assessed, with special attention paid to previous antidepressant drug therapy and psychotherapy. RESULTS Although the mean duration of dysthymia was about 30 years and almost half of the patients had previous episodes of major depression, only 41.3% had been treated with antidepressants and 56.1% with psychotherapy. A past history of major depression increased the frequency of prior antidepressant pharmacotherapy (45.7%) and psychotherapy (59.4%) compared with no history of major depression (36.8% and 40.9%, respectively). Comorbid personality disorder increased the likelihood of prior psychotherapy (70.7% vs. 49.6%) while having no effect on past pharmacotherapy. A history of substance abuse did not affect the history of antidepressant or psychotherapy treatment. In this study, dysthymia and psychosocial outcomes improved with sertraline and imipramine treatment. CONCLUSION Dysthymic patients in this sample were significantly undertreated. Newer antidepressant agents may alter the potential for pharmacotherapy interventions in this vulnerable population.
Composition profiling of piezoelectric PZT thin films deposited onto Cu coated polymer substrates

In this work, we investigate the composition profile of nanocrystalline Pb(Zr, Ti)O3 (PZT) thin films deposited by means of reactive magnetron sputtering from 200 mm diameter metallic targets (Pb, Ti, Zr). High-power pulse sputtering has been employed for alternatively the Zr- or Ti-target. Composition analysis and profiling was performed by means of X-ray photoelectron spectroscopy (XPS) and Rutherford backscattering (RBS). RBS data was recalibrated to exclude hydrogen content not determined by XPS. Advantages and drawbacks of both methods for PZT composition profiling are discussed.
EXAMINATION OF UNDERGROUND MINER DATA FOR RADON PROGENY SIZE REDUCTION AS CAUSE OF HIGH RADON “INVERSE” DOSE RATE EFFECT

Radon progeny measurements of particle size distributions show that at high radon levels the distributions decrease in arithmetic mean diameters (AMD)—apparently due to increased neutralization rates affected by high radon concentrations. The radon concentration threshold for this diameter decrease effect (enhanced deposition effect, EDE), decreases with increased humidity. From graded screen array measurements, in a test chamber the AMD’s are known vs. radon concentration. Knowing all the necessary parameters and using the ICRP 66 human respiratory tract model, the reduction in human lung dose rate per unit radon concentration was computed to be a factor of 2.5 in the test chamber. Supported by other work, this implies that the underground miners must experience a similar lung dose reduction. A prior estimate of a factor of 4 was obtained for the miners, but with only an estimate of the crucially important mine humidity distributions. Here a re-evaluation, using more realistic values for a representative mine work area surface to volume ratio and using in-mine measured humidity data at 108 mine work locations in 15 different mines, the re-computed estimate for the EDE miner lung dose rate reduction was 4.3. Analyzing separately in-mine data in unventilated locations finds a greater transition rate of the EDE lung dose reduction. These results are affirmed by measured mine progeny to radon concentration ratios, mine deposition rates and miners’ individual work shift exposures at the North Alice, Utah mine. In comparing our data with other radon “inverse” dose rate effect (IDRE) data, a significant portion of the IDRE must be from reduction in lung dose from this EDE and not from decreased lung cancer incidence per progeny lung dose. We offer the only currently plausible answer for IDRE. This does not negate any bystander effects at the very low radon concentrations where other data are least accurate.
Factors Associated With Hepatic Fibrosis In Patients With Chronic Hepatitis C: A Retrospective Study of a Large Cohort of U.S. Patients

Goals To determine the risk factors for stage 3 and 4 fibrosis in a large cohort of U.S. patients with chronic hepatitis C (CHC). Background Multiple host and viral factors affect the outcomes of CHC. Further defining the pathogenic roles of these factors in CHC progression will lead to improving management of this disease. Study Retrospective study of a large cohort of US patients with CHC. Results Of the 460 patients, 331 were males and 129 were females with mean age of 48.4±8.0 years, and 191 (41.7%) had stage 3 and 4 fibrosis. Clinically, a multivariate analysis revealed that age of ≥60 years at presentation, the estimated duration of hepatitis C virus (HCV) infection ≥25 years, a body mass index ≥30 kg/m2, and a history of diabetes mellitus were independently associated with stage 3 and 4 fibrosis, after adjusting for history of alcohol use. Laboratorially, a multivariate analysis revealed that aspartate aminotransferase (AST) ≥2×upper limit of normal (ULN), alpha fetoprotein ≥15 μg/L, and presence of grade 2 and 3 steatosis were independently associated with stage 3 and 4 fibrosis, after adjusting for alanine aminotransferase ≥2×upper limit of normal, AST/alanine aminotransferase ratio ≥1, HCV genotyping, transferrin saturation, and a histology activity index score ≥7. Conclusions The present study indicated that elderly, longer duration of HCV infection, obesity, and history of diabetes mellitus are independent clinical parameters associated with advanced fibrosis, whereas elevated AST, alpha fetoprotein, and presence of grade 2 and 3 steatosis are independent laboratorial parameters associated with stage 3 and 4 fibrosis in patients with CHC.
Inducible Heat Shock Protein 70 Promotes Myelin Autoantigen Presentation by the HLA Class II1

In this study, we investigated the role of the inducible form of heat shock protein 70 (hsp70) in the presentation of the major putative autoantigen in multiple sclerosis, myelin basic protein (MBP), in the context of appropriate MHC class II. By coimmunoprecipitation, we found that MBP is associated with hsp70 in APC in an ATP/ADP-dependent manner. Additionally, using confocal microscopy, hsp70 was detected in the endocytic pathway of APC, where it colocalized with MBP and HLA-DR. The immunodominant epitopes of MBP 85–99 and 80–99 were shown to bind selectively and specifically to hsp70 by surface plasmon resonance. The functional significance of MBP interaction with hsp70 was demonstrated by the detection of enhanced responses of an MBP-specific T cell hybridoma to MBP and MBP 80–99 with increasing levels of hsp70 and reduced responses when hsp70 expression was diminished within APC-expressing DRA*0101, DRB1*1501 (DR1501). However, when MBP 85–99 was used as the stimulus, T cell hybridoma responses were not enhanced by hsp70 overexpression within APC, suggesting that hsp70 contributes to Ag processing rather than Ag presentation. The importance of a direct association between MBP and hsp70 in the presentation pathways was demonstrated by enhanced efficacy of MBP presentation by APC transfected with a plasmid vector encoding a fusion hsp70-MBP protein. This is the first report on the involvement of self-inducible hsp70 in MHC class II-dependent autoantigen processing by APC. It implicates that aberrant self hsp expression may lead to the enhancement/modulation of autoimmune responses.
Translational control of eukaryotic gene expression

Translational control mechanisms are, besides transcriptional control and mRNA stability, the most determining for final protein levels. A large number of accessory factors that assist the ribosome during initiation, elongation, and termination of translation are required for protein synthesis. Cap-dependent translational control occurs mainly during the initiation step, involving eukaryotic initiation factors (eIFs) and accessory proteins. Initiation is affected by various stimuli that influence the phosphorylation status of both eIF4E and eIF2 and through binding of 4E-binding proteins to eIF4E, which finally inhibits cap- dependent translation. Under conditions where cap-dependent translation is hampered, translation of transcripts containing an internal ribosome entry site can still be supported in a cap-independent manner. An interesting example of translational control is the switch between cap-independent and cap-dependent translation during the eukaryotic cell cycle. At the G1-to-S transition, translation occurs predominantly in a cap-dependent manner, while during the G2-to-M transition, cap-dependent translation is inhibited and transcripts are predominantly translated through a cap-independent mechanism.
Black-Scholes Model: an Analysis of the Influence of Volatility

Black-Scholes Model An Analysis of the Influence of Volatility by Cornelia Krome The University of Wisconsin-Milwaukee, 2017 Under the Supervision of Professor Richard H. Stockbridge In this thesis the influence of volatility in the Black-Scholes model is analyzed. The deduced Black-Scholes formula estimates the price of European options. Contrary to the other parameters of the formula, the future volatility of the underlying asset cannot be observed in the market. The parameter needs to be assumed in order to calculate the option price. An inaccurate assumption may lead to an erroneous volatility. It is studied how a falsely assumed volatility impacts on the option price. Empirical simulations will be carried out to get an impression of possible errors in the computations. Afterwards, those results will be discussed and linked with an evaluation of potential risks.