Miracle-dz/UniFAR-FTUs huggingface dataset:
Parkin protects against tyrosinase‐mediated dopamine neurotoxicity by suppressing stress‐activated protein kinase pathways

Parkinson’s disease (PD) motor symptoms are caused by degeneration of nigrostriatal dopaminergic (DAergic) neurons. The most common causes of hereditary PD are mutations in the PARKIN gene. The ubiquitin ligase parkin has been shown to mediate neuroprotection in cell culture and in vivo, but the molecular mechanisms are not well understood. We investigated the effects of parkin in a human SH‐SY5Y neuroblastoma cell culture model of PD, in which transcriptional induction of the enzyme tyrosinase causes a neurotoxic overproduction of cellular DA and its oxidative metabolites. Tyrosinase induction caused formation of reactive oxygen species in the cytosol and mitochondria, and neurotoxicity via activation of apoptotic stress‐activated protein kinases and caspase 3. Stable transfection of wild‐type parkin suppressed tyrosinase‐induced apoptosis, and PD‐associated mutations abolished the neuroprotective effect of parkin. Expression of wild‐type parkin did not affect reactive oxygen species production, but attenuated the tyrosinase‐induced activation of both c‐Jun N‐terminal kinase and p38 mitogen‐activated protein kinase as well as their cognate mitogen‐activated protein kinase kinases. PD‐associated mutations differentially affected the anti‐apoptotic signaling of parkin. Thus, parkin contributes to DAergic neuroprotection by suppression of apoptotic stress‐activated protein kinase pathways.
Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate, and Fluorouracil in operable breast cancer.

PURPOSE To assess the clinical relevance of different sequences of doxorubicin (DOX) and cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with operable breast cancer at risk of disease relapse. PATIENTS AND METHODS Two randomized trials were activated in the early 1980s. The first study, in patients with one to three involved nodes, was intended to assess the effectiveness of intravenous (i.v.) CMF given every 3 weeks for 12 courses versus eight courses of the same CMF regimen followed by four courses of full-dose DOX (CMF-->DOX). The second study, in patients with more than three involved nodes, compared four courses of full-dose DOX sequentially followed by eight courses of i.v. CMF (DOX-->CMF) versus alternating two courses of the same CMF regimen with one course of DOX (CMF/DOX) for a total of 12 courses. RESULTS After a median observation of 210 months, no statistically significant difference was documented in the first study (relapse-free survival hazard rate [HR], 1.06; total survival HR, 1.03). In contrast, the delivery of DOX first, followed by CMF significantly reduced the risk of disease relapse (HR, 0.68; 95% CI, 0.54 to 0.87; P =.0017) and death (HR, 0.74; 95% CI, 0.57 to 0.95; P =.018) compared with the alternating regimen. CONCLUSION Anthracycline-containing regimens can further reduce the odds of relapse and death compared with CMF. However, the findings observed in our trials emphasize that the relative merits of anthracycline adjuvant programs also can depend on the modality of administration and must be assessed in properly designed trials in which the magnitude of the benefits can be weighed against potential risks.
The Bitcoin Mining Game: On the Optimality of Honesty in Proof-of-work Consensus Mechanism

We consider a game in which Bitcoin miners compete for a reward of each solved puzzle in a sequence of them. We model it as a sequential game with imperfect information, in which miners have to choose whether or not to report their success. We show that the game has a multiplicity of equilibria and we analyze the parameter constellations for each of them. In particular, the minimum requirement to find it optimal not to report is decreasing with the number of miners who are not reporting, and increasing the heterogeneity among players reduces the likelihood that they choose not to report.
Comparison of the transcutaneous bilirubinometers BiliCare and Minolta JM-103 in late preterm and term neonates

Abstract Objectives: To assess the agreement of transcutaneous bilirubin (TcB) measurement with the Bilicare™ System in comparison to TcB measured with JM-103™ and total serum bilirubin (TSB). Methods: Caucasian infants with gestational age ≥35 weeks with non-hemolytic jaundice received TcB measurement with both Bilicare™ and JM-103™ devices. TSB was also obtained in infants at risk of phototherapy. Results: We studied 458 infants measuring TcB with Bilicare™ and JM-103™, correlating the results and with TSB. The mean difference ± 2SD between Bilicare™ and JM-103™ TcB was 2.02 ± 4.46 mg/dL and decreased from 2.88 ± 3.17 to 1.20 ± 4.55, and to −0.95 ± 4.58 mg/dL at mild, moderate and high TcB values, respectively. Conclusions: Bilicare™ and JM-103™ TcB measurements are well correlated, but Bilicare™ over-estimates TcB for mild and moderate values and under-estimates it for high values compared to JM-103™. This could increase the prescription of TSB measurements for less serious cases and decrease them in the most worrisome.
The Social Contexts of Drug Offers and Their Relationship to Drug Use of Rural Hawaiian Youths

This article examines the differences in drug offers and recent drug use between Hawaiian and non-Hawaiian youths residing in rural communities, and the relationship between drug offers and drug use of Hawaiian youths in these communities. Two hundred forty-nine youths (194 Hawaiian youths) from 7 different middle or intermediate schools completed a survey focused on the social context of drug offers. Hawaiian youths in the study received significantly more offers from peers and family, and had significantly higher rates of recent alcohol and marijuana use, compared with non-Hawaiian youths. Logistic regression analysis indicated that the social context differentially influenced drug use of Hawaiian youths, with family drug offers and context influencing overall drug use and the use of the widest variety of substances. Implications for prevention practices are discussed.
Obstetric pain relief and its association with remembrance of labor pain at two months and one year after birth

The association between obstetric pain relief and long-term memory of pain is poorly researched in spite of the fact that a woman's memory of childbirth may affect her emotional wellbeing and future reproduction. The aim of this study was to investigate the association between epidural analgesia and other forms of pain relief, and memory of pain at two months and one year after birth. A national sample of 2482 Swedish speaking women with vaginal delivery or emergency cesarean section preceded by labor were followed from early pregnancy to one year after birth. Data were collected by three postal questionnaires: in early pregnancy, and two months and one year after the birth. Recollection of intense pain at two months and one year was associated with high rates of pain relief, and this was most obvious regarding epidural analgesia in first-time mothers. When comparing women with the same pain score at two months postpartum who had and who did not have an epidural, the first group seemed to have greater difficulty forgetting pain 10 months later. Possible explanations of these findings are discussed.
Response of müller cells to growth factors alters with time in culture

We have developed an explant culture technique, using the retinae of newborn guinea pigs, that reliably yields cultures of Müller cells showing uniform morphology and phenotype. Since the guinea pig retina is avascular and lacks astrocytes, Müller cells are the only glial cell‐type and the only vimentin‐positive population present. Virtually all passaged cells (<98%) contain vimentin‐positive intermediate filaments and no glial fibrillary acidic protein (GFAP) has been detected using a range of GFAP antibodies known to label astrocytes in the guinea pig optic nerve. Most vimentin‐positive cells were also labeled with an antibody to carbonic anhydrase II, an enzyme which in the retina is specific for Müller cells. Proliferating Müller cells were identified within the inner nuclear layer of retinal fragments as early as 2 days in culture using bromodeoxyuridine (BrdU) and vimentin double labeling. Cultured Müller cells change their growth characteristics with successive passaging. The length of the cell cycle increases from 25.4 h for cells at first passage, to 66.7 h for cells at fourth passage. Altered responses to mitogens were also observed with passaging. First‐passage cultures responded to basic fibroblast growth factor (bFGF) but not to several other factors tested including interleukin‐2 (IL‐2). In contrast, older cultures were highly responsive to IL‐2 but showed a minimal response to bFGF. The altered responsiveness to mitogens observed in vitro may be relevant to changes in growth control of Müller cells in the developing and mature retina.
CT stress perfusion imaging for detection of haemodynamically relevant coronary stenosis as defined by FFR

Objectives To evaluate the diagnostic accuracy (DA) of CT-myocardial perfusion imaging (CT-MPI) and a combined approach with CT angiography (CTA) for the detection of haemodynamically relevant coronary stenoses in patients with both suspected and known coronary artery disease. Design Prospective, non-randomised, diagnostic study. Setting Academic hospital-based study. Patients 65 patients (42 men age 70.4±9) with typical or atypical chest pain. Interventions CTA and CT-MPI with adenosine stress using a fast dual-source CT system. At subsequent invasive angiography, FFR measurement was performed in coronary arteries to define haemodynamic relevance of stenosis. Main outcome measures We tried to correlate haemodynamically relevant stenosis (FFR < 0.80) to a reduced myocardial blood flow (MBF) as assessed by CT-MPI and determined the DA of CT-MPI for the detection of haemodynamically relevant stenosis. Results Sensitivity and negative predictive value (NPV) of CTA alone were very high (100% respectively) for ruling out haemodynamically significant stenoses, specificity, Positive predictive value (PPV) and DA were low (43.8, 67.3 and 72%, respectively). CT-MPI showed a significant increase in specificity, PPV and DA for the detection of haemodynamically relevant stenoses (65.6, 74.4 and 81.5%, respectively) with persisting high sensitivity and NPV for ruling out haemodynamically relevant stenoses (97% and 95.5% respectively). The combination of CTA and CT-MPI showed no further increase in detection of haemodynamically significant stenosis compared with CT-MPI alone. Conclusions Our data suggest that CT-MPI permits the detection of haemodynamically relevant coronary artery stenoses with a moderate DA. CT may, therefore, allow the simultaneous assessment of both coronary morphology and function.
Rheology of non-Brownian suspensions of rough frictional particles under shear reversal: A numerical study

We perform particle scale simulations of suspensions submitted to shear reversal. The simulations are based on the Force Coupling method, adapted to account for short range lubrication interactions together with direct contact forces between particles, including surface roughness, contact elasticity, and solid friction. After shear reversal, three consecutive steps are identified in the viscosity transient: An instantaneous variation, followed by a rapid contact force relaxation, and finally a long time evolution. The separated contributions of hydrodynamics and contact forces to the viscosity are investigated during the transient, allowing a qualitative understanding of each step. In addition, the influence of the contact law parameters (surface roughness height and friction coefficient) on the transient is evaluated. Concerning the long time transient, the difference between the steady viscosity and minimum viscosity is shown to be proportional to the contact contribution to the steady viscosity, allowi.
Glycolic acid versus Jessner's solution: which is better for facial acne patients? A randomized prospective clinical trial of split-face model therapy.

BACKGROUND Many clinicians perform glycolic acid peels for facial acne patients, but there has not been a well-controlled study to compare this new therapy with other conventional modalities. OBJECTIVE To compare the effectiveness of treatment and side effects in the treatment of facial acne by two agents, 70% glycolic acid and Jessner's solution. METHODS Twenty-six patients with facial acne were treated simultaneously with 70% glycolic acid and Jessner's solution biweekly on each side of the face. The treatment sides were randomized and the evaluation of treatment was done biweekly by a blinded evaluator who did not know the randomization code. Dr. Cunliffe's acne grading system was used for objective comparison. All patients were also asked about the improvement of facial acne and about the side effects experienced. Finally, the patients answered the preference test between the 2 peeling methods. RESULTS Acne grading of both treatments improved after 3 treatment sessions. However, there were no significant differences in treatment effects between the 2 methods. As far as side effects were concerned, sites treated with Jessner's solution showed a significantly increased degree of exfoliation compared to glycolic acid (p < 0.01). CONCLUSION Glycolic acid is less widely used than Jessner's solution due to its inconvenient application technique. But considering the equal treatment effect and lesser degree of exfoliation in glycolic acid, we would recommend the use of glycolic acid over Jessner's solution for acne patients.
Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation

Background and aims The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics at the time of presentation vary considerably among different parts of the world and over time. The number of patients seen at our institution has increased as compared to a period 20 years earlier. We investigated baseline characteristics of patients with hepatocellular carcinoma such as cirrhosis, hepatitis virus markers, age at presentation and stage of the tumour in an area with low prevalence of viral hepatitis. Methods All 245 patients seen at the Department of Gastroenterology and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998 were included in this retrospective study, and 19 different clinical characteristics were studied. Results The median age at detection of HCC was 63.3 years, and alcoholic liver disease (35.1%) and hepatitis C virus (HCV) infection (36.7%) were the most frequent underlying diseases. Both chronic alcoholism and HCV infection as risk factors were present in 6.9% of the patients. Liver cirrhosis was present in 86.5%. At the time of diagnosis, 43.5% had multi‐nodular tumours. Of the remaining patients with a single nodule, only 10% had HCC ⩽ 2 cm. Most of our patients presented at a late stage of the disease (TNM stage 3 29.4%, TNM stage 4 69.7%; Okuda stage 2 65.7%, Okuda stage 3 18.0%). Due to the late stage of the disease at the time of presentation, 145 patients (59.2%) received palliative care only, 24 (9.8%) underwent liver resection, 38 (15.5%) liver transplantation and 38 (15.5%) chemotherapy. Conclusions In this large single‐centre series of HCC, the dominant contribution of HCV infection and chronic alcohol abuse as the underlying aetiology is documented. Diagnosis is usually made very late as reflected in the high proportion of patients in TNM stages 3 and 4 or Okuda stages 2 and 3. This resulted in a high percentage of patients who received palliative care only and very few who were eligible for treatment modalities with curative potential such as resection and liver transplantation. Eur J Gastroenterol Hepatol 12:941‐948
Identification of Tissue Transglutaminase as a Novel Molecule Involved In Human CD8+ T Cell Transendothelial Migration 1

During inflammation, T lymphocytes migrate out of the blood across the vascular endothelium in a multistep process. The receptors mediating T cell adhesion to endothelium are well characterized; however, the molecules involved in T cell transendothelial migration (TEM) subsequent to lymphocyte adhesion to the endothelium are less clear. To identify receptors mediating TEM, mAbs were produced against human blood T cells adhering to IFN-γ-activated HUVEC in mice and tested for inhibition of lymphocyte TEM across cytokine-activated HUVEC. Most of the mAbs were against β1 and β2 integrins, but one mAb, 6B9, significantly inhibited T cell TEM across IFN-γ, TNF-α, and IFN-γ plus TNF-α-stimulated HUVEC, and did not react with an integrin. 6B9 mAb did not inhibit T cell adhesion to HUVEC, suggesting that 6B9 blocked a novel pathway in T cell TEM. The 6B9 Ag was 80 kDa on SDS-PAGE, and was expressed by both blood leukocytes and HUVEC. Immunoaffinity purification and mass spectrometry identified this Ag as tissue transglutaminase (tTG), a molecule not known to mediate T cell TEM. Treatment of HUVEC with 6B9 was more effective than treatment of T cells. 6B9 blockade selectively inhibited CD4−, but not CD4+, T cell TEM, suggesting a role for tTG in recruitment of CD8+ T lymphocytes. Thus, 6B9 is a new blocking mAb to human tTG, which demonstrates that tTG may have a novel role in mediating CD8+ T cell migration across cytokine-activated endothelium and infiltration of tissues during inflammation.
No major differences in incidence of temporal arteritis in northern and western Norway compared with reports from southern Norway

In Europe the highest incidence of temporal arteritis (TA) is found in the Scandinavian countries (1, 2), and lower Mediterranean countries (3). It has been suggested that this north – south gradient can be explained by differences in climate and/or environmental and genetic factors (for review see Reference 4). For example, an annual incidence of 32.8 per 100 000 individuals age w50 years has been reported from southern Norway [‘Kristiansand.S’ city, latitude 58‡,10 North (1)], whereas in northwest Spain [Lugo, at a latitude of ,43‡ (3)] an incidence as low as 6 per 100 000 individuals age w50 has been found. To explore a potential association between incidence of TA and an increasing latitude in Norway we examined the incidence of TA from two selected areas, one in western (‘Ålesund city’, latitude 62‡, 28 North) and one in northern Norway (‘Bodø city’, latitude 67‡, 17 North) and compared these with reports from southern Norway (1, 2). To make a direct comparison with one of the reports from southern Norway possible, we examined the same 5-year period (1992 – 96) and applied the same retrospective method to identify TA patients as that used in the study by Haugeberg et al. (1). A total of 70 patients, mean age 73 years were diagnosed to have TA (northern part 11 males, 17 females and western part 9 males, 33 females). Among these patients, a total of 66 patients fulfilled the 1990 American College of Rheumatology (ACR) criteria (traditional format) for TA (5), and four patients had a positive temporal artery biopsy of giant cell arteritis, but did not fulfil the ACR criteria (missing clinical data in the case notes). As shown in Table 1, no major differences in incidence of TA in northern and western Norway compared with the report from southern Norway (1) were found, despite the large differences in latitudes between the examined areas. No major difference was found for the clinical findings either. At disease onset all patients were older than 50 years, 91% had erythrocyte sedimentation rate (ESR) §50 mm/h, 64% had new headache, 77% had systemic features,
Evaluation of chopped switchgrass as a litter material.

An alternative broiler litter to pine shavings may be switchgrass, a high yielding forage crop (8-12 tons per acre) that can grow across the Southeastern U.S. A study was conducted to determine the efficacy of chopped switchgrass as a litter material for broiler chickens. Pine Shavings (PS) and Switchgrass (SG) were used as litter treatments with 10 replications each. Body weight, body weight gain, feed consumption, feed conversion, carcass weights and mortality were not different between treatments. However, the incidence of foot pad dermatitis was significantly decreased with SG litter. Live performance and carcass weights were not affected by using chopped SG as a litter material when rearing broilers over a short duration (one flock cycle).
Computational modelling of lipid bilayers with sphingomyelin and sterols

This thesis is based on atom-scale molecular dynamics simulations on lipid bilayers. The study concentrates on structural and dynamic properties of lipid bilayers, involving three lipid classes that are the main constituents of, for example, eukaryotic plasma membranes: phosphatidylcholines (PCs), sphingomyelins (SMs) and sterols. The discussion in the thesis starts from the simplest bilayers that are comprised of single lipid components, and gradually moves towards more complex systems, approaching a better description of biological membranes. Studies on single-component bilayers concentrate on the properties of SM. In a comparison with a structurally similar PC, it is shown that the packing of SM in a bilayer is more compact and that the lipids are more ordered than in a PC bilayer. Additionally, unsaturation increases the fluidity of SM bilayer less than typically in PC bilayers. The above differences in the bilayer properties of SM and PC are explained by detailed analysis of the intraand intermolecular hydrogen bonding in the SM bilayer. The results on the effects of chain length on SM bilayers are mainly involved with the bilayer thickness and the interdigitation of the longer chains through the bilayer centre. The studies on sterols involves two parts. First, the molecular interactions of cholesterol (CHOL) with PC and SM lipids are characterised in detail. In particular, the aim is to reveal aspects of the SM-CHOL interaction, which has been proposed to be a key factor in the formation of lateral domains called lipid rafts in biological membranes. Second, the properties of bilayers with binary mixtures of PC and different sterols are discussed. It is shown that the acyl chain order in the studied systems is correlated with the tilt of
The hydrated and anhydrous gold(III) tetrachloride salts of L-ecgonine, an important forensic toxicology marker for cocaine.

The structure of the hydrated gold(III) tetrachloride salt of L-ecgonine {hydronium tetrakis[(1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2. 1]octane-2-carboxylate pentakis[tetrachloridoaurate(III)] hexahydrate}, (C(9)H(16)NO(3))(4)(H(3)O)[AuCl(4)](5). 6H(2)O, demonstrates an unprecedented stoichiometric relationship between the cations and anions in the unit cell. The previous tropane alkaloid structures, including the related hydrochloride salts, all have a cation-anion ratio of 1:1, as does the anhydrous salt described here, namely (1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2. 1]octane-2-carboxylate tetrachloridoaurate(III), (C(9)H(16)NO(3))[AuCl(4)]. The hydrated salt, however, consists of four monopositive N-protonated units of the alkaloid and five [AuCl(4)](-) counter-ions, plus seven solvent water molecules. The H atom required for change balance has been assigned to a water molecule. In addition, the hydrate has a novel arrangement, with all seven of the water molecules and all of the O atoms in the cations participating in an alternating arrangement of interleaved sheets of the anionic species. Both the hydrate and the anhydrous salt of the same toxicologically important marker for cocaine show that the cation and anion are in close proximity to each other, as was found in the gold(III) tetrachloride salt of L-cocaine.