Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of mucin core proteins in extramammary Paget's disease

Extramammary Paget's disease (EPD) is a relatively common skin cancer wherein tumor cells have mucin in their cytoplasm. However, little is known about mucin expression in EPD. We examined immunohistochemically the expression of mucin core proteins (MUC1, MUC2, MUC5AC and MUC6) in 36 cases of EPD and found different patterns of expression in intraepithelial (n = 36), microinvasive (n = 13) and invasive lesions (n = 6). In normal skin, MUC1 was expressed in the sebaceous, eccrine and apocrine glands. MUC2, MUC5AC and MUC6 were not expressed in any of these. In the 36 intraepithelial lesions, MUC1 and MUC5AC were expressed in 35 and 36 lesions, respectively. MUC1 expression was also observed in all 13 microinvasive lesions and in all six invasive lesions. In contrast to the intraepithelial lesions, a decrease or loss of MUC5AC expression was observed in five out of 13 microinvasive lesions and in all six invasive lesions. MUC2 and MUC6 were not expressed in any of the EPD lesions examined. The combination of immunohistochemical staining for MUC1 and MUC5AC was useful for identifying invasive Paget cells. The decrease or loss of MUC5AC expression may have an important role in the invasive growth of Paget cells.
Sensory conflict theory and space sickness: our changing perspective.

Motion sickness is a well-known nausea and vomiting syndrome whose physical signs include vomiting and retching, pallor, cold sweating, yawning, belching, flatulence, and decreased gastric tonus. Subjective symptoms include stomach discomfort, nausea, headache, feeling of warmth, and drowsiness. The research literature has been well reviewed (1-7). Over the past hundred years, our perspective on the kinds of sensory stimulation that can cause motion sickness has broadened considerably. Originally it was assumed that motion sickness can only be caused by motion and is due to mechanical stimulation of visceral afferents or changes in cerebral blood flow caused by body motion. It was eventually recognized that people who have no inner ear balance organ function are totally immune, indicating that the malady results specifically from vestibular over-stimulation. However, by 1970 it became apparent that a more comprehensive etiologic framework was needed: some forms of motion sickness were recognized in which head and body motion is normal (that is, spectacle sickness, space sickness) or even absent (flight simulator and Cinerama sickness). We experience vigorous vestibular stimulation when we run, jump, or dance, but these activities almost never make us sick. Claremont (8) had originally suggested that mo-
Forestomach tumors induced by orally administered epichlorohydrin in male Wistar rats.

Epichlorohydrin is an epoxide compound which is widely used in various industrial fields. The mutagenic action of this compound was first demonstrated in fruit flies,3) and it has since been studied by several investigators.1,2,4) The carcinogenic activity of epichlorohydrin was tested in mice,5,6) but the findings were inconclusive. In the present experiment, the carcinogenic activity of epichlorohydrin was tested in rats, and the chemical was found to induce forestomach hyperplasias, papillomas, and carcinomas. Seventy-two, 6-week-old male outbred Wistar rats (Kiwa Animal Farm, Wakayama), weighing approximately 160g each, were used. Epichlorohydrin (Nakarai Chemicals, Ltd., Kyoto) was dissolved in drinking water freshly every day and placed in a bottle covered with black tape to protect it from the light. Four groups of rats were treated: Group 1 received 0ppm (control group); group 2, 375ppm; group 3, 750ppm; and group 4, 1500ppm. However, epichlorohydrin administration had to be stopped intermittently due to the poor condition of rats, as shown in Fig. 1. The rats were housed in wire cages in an air-conditioned room at
[Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease].

UNLABELLED AIM. To analyze changes in the serum concentrations of the morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klotho, as well as sclerostin, an osteocyte-secreted glycoprotein, in relation to the degree of hypertension, left ventricular (LV) hypertrophy, and arterial stiffness in patients with chronic kidney disease (CKD) at its different stages. SUBJECTS AND METHODS Sixty-five patients (33 men and 32 women) aged 20-65 years, including 25 with chronic glomerulonephritis, 15 with tubulointerstitial nephritis, and 25 with hypertensive nephrosclerosis, were examined. A control group consisted of 15 healthy volunteers matched to the study group patients for age and gender. Serum FGF-23 concentrations and blood pressure (BP) were measured in the all subjects. Patients with BPs > 140/80 mm Hg underwent echocardiography, followed by determination of LV mass (LVM) and calculation of LVM index. Vascular circulation, pulse wave velocity, cardiac and vascular calcifications, and vascular functional properties were estimated. RESULTS There was a strong direct Correlation between the serum concentration of FGF-23 and the stage of CKD and an inverse correlation between the levels of Klotho and sclerostin and the stage of CKD. As the glomerular filtration rate became lower, the concentration of FGF-23 increased and that of Klotho and sclerostin decreased just in Stage III CKD while hyperphosphatemia and elevated parathyroid hormone levels were noted in Stages IV-V CKD. As CKD progressed, the serum concentrations of Klotho and sclerostin were inversely correlated with the levels of phosphorus and parathyroid hormone. The degree of blood pressure elevation correlated positively with serum FGF-23 concentrations and inversely with Klotho levels. There was no significant correlation of the level of sclerostin with the degree of BP increase. The direct correlation between higher FGF-23 level and higher VLM is most pronounced in hypertensive patients. There was a strong direct relationship between FGF-23 and Klotho levels and a strong inverse relationship between sclerostin levels and pulse wave velocity. Lower Klotho concentrations were associated with the detection rate of calcifications in the heart valves and large arteries (the abdominal aorta). The reduced serum levels of Klotho and sclerostin were also correlated with concentric LV remodeling. CONCLUSION It was demonstrated that there was a clear link between increased serum FGF-23 and decreased Klotho concentration as CKD progressed, and that between arterial stiffness and calcification and myocardial remodelling regardless of traditional risk factors. More experimental and clinical studies are required to clarify the role of sclerostin in CKD.
Brexit: The Economic and Political Implications for Asia

Often trumpeted as a bastion of modern economic and political integration, the European Union (EU) has played an integral role in the development of the United Kingdom’s (UK) economy. However, in recent times, the relationship between the EU and the UK has become increasingly fragile, particularly on issues of national sovereignty, immigration, and the general bureaucratic reach of Brussels. Tension surrounding these concerns meant that on 23 June 2016, the British public voted, by way of a referendum, to leave the EU. This decision, often referred to as Brexit, has created a watershed moment in the history of the region, with implications that may have a significant impact on not only Europe, but also Asia and the wider global community. In order to make better sense of the issue, this study provides a brief synopsis of Britain’s decision to leave the EU, before providing a detailed analysis of how the Brexit decision will impact the Asian region. As part of this discussion, a series of relevant policy issues are considered.
The Homozygous Leu Variant of the Factor XIII Val34Leu Polymorphism as a Risk Factor for the Manifestation of Thrombotic Microangiopathies

The 34 Leu (100T) variant of the factor XIII Val34Leu (G100T-) polymorphism slows down fibrinolysis and has been proposed as a thrombotic risk factor. In this pilot study, we enrolled 40 patients (mean age ± SD = 38 ± 11 years) and 728 controls to assess the role of this genetic variant for the manifestation of thrombotic microangiopathies. From the genotype prevalences, an increased manifestation risk for carriers of the TT genotype (homozygous Leu variant) of the factor XIII Val34Leu (G100T-) polymorphism was calculated (odds ratio [OR] = 2.44; 95% confidence interval [CI] = 0.8-7.6; P = .11). This association was statistically significant for patients with thrombotic thrombocytopenic purpura—hemolytic-uremic syndrome (TTP-HUS) (OR = 6.6; 95% CI = 1.7-25.9; P = .006). Our data suggest a role of the homozygous Leu variant of the factor XIII Val34Leu polymorphism in the manifestation of thrombotic microangiopathies. Decreased fibrinolysis in the presence of this genetic variant provides a plausible explanation for this association.
Surface-Height Determination of Crevassed Glaciers—Mathematical Principles of an Autoadaptive Density-Dimension Algorithm and Validation Using ICESat-2 Simulator (SIMPL) Data

Glacial acceleration is a main source of uncertainty in sea-level-change assessment. Measurement of ice-surface heights with a spatial and temporal resolution that not only allows elevation-change calculation, but also captures ice-surface morphology and its changes is required to aid in investigations of the geophysical processes associated with glacial acceleration. The Advanced Topographic Laser Altimeter System aboard NASA’s future ICESat-2 Mission (launch 2017) will implement multibeam micropulse photon-counting lidar altimetry aimed at measuring ice-surface heights at 0.7-m along-track spacing. The instrument is designed to resolve spatial and temporal variability of rapidly changing glaciers and ice sheets and the Arctic sea ice. The new technology requires the development of a new mathematical algorithm for the retrieval of height information. We introduce the density-dimension algorithm (DDA) that utilizes the radial basis function to calculate a weighted density as a form of data aggregation in the photon cloud and considers density an additional dimension as an aid in autoadaptive threshold determination. The autoadaptive capability of the algorithm is necessary to separate returns from noise and signal photons under changing environmental conditions. The algorithm is evaluated using data collected with an ICESat-2 simulator instrument, the Slope Imaging Multi-polarization Photon-counting Lidar, over the heavily crevassed Giesecke Brær in Northwestern Greenland in summer 2015. Results demonstrate that ICESat-2 may be expected to provide ice-surface height measurements over crevassed glaciers and other complex ice surfaces. The DDA is generally applicable for the analysis of airborne and spaceborne micropulse photon-counting| lidar data over complex and simple surfaces.
Long‐term outcome after neo‐adjuvant chemotherapy for breast cancer in BRCA1/2 carriers

Annick Wong Wong Keet, Munir Al-Rafae, Pierre O. Chappuis, Jean-S ebastien Brunet, Parviz Ghadirian and William D. Foulkes* Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada Internal Medicine Residency Training Program, McGill University, Montreal, Quebec, Canada Department of Oncology, McGill University, Montreal, Quebec, Canada Oncogenetics and Cancer Prevention Unit, Division of Oncology, Department of Internal Medicine, Division of Genetic Medicine, Department of Genetic Medicine and Laboratory, University Hospitals, Geneva, Switzerland Pharsight Corporation, Montreal, Quebec, Canada Epidemiology Research Unit, Hotel-Dieu Hospital, CRCHUM, Université de Montréal, Montréal, Quebec, Canada
Injurious ventilation strategies cause systemic release of IL‐6 and MIP‐2 in rats in vivo *

In vivo experiments showed no increased production of tumour necrosis factor (TNF) in response to injurious ventilation strategies in otherwise untreated animals. Because interleukin‐6 (IL‐6) and macrophage inflammatory protein‐2 (MIP‐2) are more sensitive markers of ventilation‐induced cytokine release, serum and bronchoalveolar lavage (BAL) samples were examined for these mediators. Eighty‐five adult rats were randomized to three different ventilation strategies. Rats were ventilated with low pressures and low tidal volumes [13/3; peak inspiratory pressure (PIP)/positive end‐expiratory pressure (PEEP) in cmH2O], the second group of rats was ventilated with high pressures and low PEEP resulting in high tidal volumes (32/6), and the third group was ventilated with the same high pressures but without PEEP (32/0). Animals were ventilated either for 90 or 240 min, subsequently serum and BAL were collected for analyses on IL‐6 and MIP‐2 content. Non‐ventilated animals served as healthy controls. Ventilation with 32/0 for 90 or 240 min, led to increased serum IL‐6 levels. Serum MIP‐2 levels were increased by ventilation with 32/6 (90 min) and 32/0 (240 min). Ventilation under any condition, even at 13/3, resulted in elevated MIP‐2 levels in the BAL fluid. Even at normal pressures pulmonary MIP‐2 levels were increased, suggesting that ventilation may promote pro‐inflammatory responses in healthy subjects.
Peroxisome Proliferator–Activated Receptor &agr; Gene Regulates Left Ventricular Growth in Response to Exercise and Hypertension

Background—Left ventricular hypertrophy (LVH) occurs as an adaptive response to a physiological (such as exercise) or pathological (valvular disease, hypertension, or obesity) increase in cardiac work. The molecular mechanisms regulating the LVH response are poorly understood. However, inherited defects in fatty acid oxidation are known to cause severe early-onset cardiac hypertrophy. Peroxisome proliferator–activated receptor &agr; (PPAR&agr;) regulates genes responsible for myocardial fatty acid oxidation and is downregulated during cardiac hypertrophy, concomitant with the switch from fatty acid to glucose utilization. Methods and Results—The role of PPAR&agr; in left ventricular growth was investigated in 144 young male British Army recruits undergoing a 10-week physical training program and in 1148 men and women participating in the echocardiographic substudy of the Third Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg study. A G/C polymorphism in intron 7 of the PPAR&agr; gene significantly influenced left ventricular (LV) growth in response to exercise (P =0.009). LV mass increased by 6.7±1.5 g in G allele homozygotes but was significantly greater in heterozygotes for the C allele (11.8±1.9 g) and in CC homozygotes (19.4±4.2 g). Likewise, C allele homozygotes had significantly higher LV mass, which was greater still in hypertensive subjects, and a higher prevalence of LVH in the Third MONICA Augsburg study. Conclusions—We demonstrate that variation in the PPAR&agr; gene influences human left ventricular growth in response to exercise and hypertension, indicating that maladaptive cardiac substrate utilization can play a causative role in the pathogenesis of LVH.
The effect of anaesthetic agents on induction, recovery and patient preferences in adult day case surgery: a 7‐day follow‐up randomized controlled trial

Background and objective: To compare induction, pre‐ and post‐discharge recovery characteristics and patient preferences between four anaesthetic regimens in adult day‐surgery. Methods: Randomized controlled trial. In all, 1158 adults assigned to: propofol induction and maintenance, propofol induction with isoflurane/N2O, or sevoflurane/N2O maintenance, or sevoflurane/N2O alone. We prospectively recorded induction and pre‐discharge recovery characteristics, collected 7‐day post‐discharge recovery characteristics using patient diaries and patient preferences by telephone follow‐up. Results: Recruitment rate was 73% ‐ of the 425 refusals, 226 were not willing to risk a volatile induction. During induction, excitatory movements and breath holding were more common with sevoflurane only (P < 0.01). Injection pain and hiccup were more common with propofol induction (P < 0.01). In the recovery room and the postoperative ward, both nausea and vomiting were more common with sevoflurane only (P < 0.01). This difference disappeared within 48 h. There was no difference between groups in the mental state on awakening, recovery time, time to discharge or overnight admissions; then was also no difference in pain between the four groups for each of the seven postoperative days (P < 0.01), nor any differences in concentration or forgetfulness. Patients took 6.5 days (95% CI: 6.0‐7.0, n = 693) to resume normal activities. Patients who received sevoflurane only were more likely to recall an unpleasant induction and least likely to want the same induction method again (P < 0.01). Conclusion: Differences in outcome between the four regimens are transient; sevoflurane is not an ideal sole agent for adult day case anaesthesia and, in this setting, patients base their preferences for future anaesthetics on the method of induction.
Enhanced resolution of glycosylphosphatidylinositol‐anchored and transmembrane proteins from the lipid‐rich myelin membrane by two‐dimensional gel electrophoresis

Two‐dimensional gel electrophoresis (2‐DE) has become a powerful and widely used technique for proteomic analyses. However, the limited ability of 2‐DE to resolve transmembrane and glycosylphosphatidylinositol (GPI)‐anchored proteins has slowed the identification of proteins from membrane‐rich biological samples. Myelin is an unusually lipid‐rich membrane with relatively few major proteins but many quantitatively minor proteins, most of which have an unknown identity and/or function. The goal of this study was to identify the optimal conditions of 2‐DE for the separation of myelin proteins. We have identified two detergents, the nonionic n‐dodecyl β‐D‐maltoside and the zwitterionic amidosulfobetaine ASB‐14, that are more effective in solubilizing myelin proteins than the commonly used zwitterionic detergent 3‐[(3‐cholamidopropyl)‐ dimethylammonio]‐1‐propanesulfonate (CHAPS). These detergents significantly enhance the solubility of both transmembrane (e.g., the highly hydrophobic and multiply acylated myelin proteolipid protein) and GPI‐anchored (e.g., contactin and neuronal cell adhesion molecule) myelin proteins and enable their resolution by 2‐DE. We conclude that these detergents are effective tools for the 2‐DE analysis of myelin, and that they may be more generally useful for the analysis of membrane‐rich biological samples.
Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design

ABSTRACT Single-chain derivatives of JRFL gp120 linked to the first two domains of human CD4 (gp120-CD4D12) or to the CD4 miniprotein analog CD4M9 (gp120-M9), have been constructed. Biacore studies revealed that gp120-CD4D12 and gp120-M9 bound to antibody 17b with dissociation constants of 0.8 and 25 nM, respectively, at pH 7.0, while gp120 alone did not bind. The binding of gp120-CD4D12 to 17b is not affected by the addition of excess soluble CD4D12, while the binding of gp120-M9 is enhanced. This finding indicates that the M9 component of the single chain interacts relatively weakly with gp120 and can be displaced by soluble CD4D12. Immunogenicity studies of gp120, gp120-CD4D12, and gp120-M9 were carried out with guinea pigs. All three molecules were highly immunogenic. The resulting antisera were examined for neutralizing activities against various human immunodeficiency virus type 1 isolates. Broadly neutralizing activity was observed only with sera generated against gp120-CD4D12. These antisera were depleted of anti-CD4D12 antibodies by being passed over a column containing immobilized CD4D12. The depleted sera showed a loss of broadly neutralizing activity. Sera that were affinity purified over a column containing immobilized gp120-M9 also lacked such neutralizing activity. This finding suggests that the broadly neutralizing response observed is exclusively due to anti-CD4 antibodies. Competition experiments showed that only antisera generated against gp120-CD4D12 competed with the CD4i antibody 17b and that this activity was not affected by depletion of anti-CD4 antibodies. The data indicate that although antibodies targeting the CD4i epitope were generated by the gp120-CD4D12 immunogen, these antibodies were nonneutralizing.
A survey of beef muscle color and pH.

The objectives of this study were to define a beef carcass population in terms of muscle color, ultimate pH, and electrical impedance; to determine the relationships among color, pH, and impedance and with other carcasses characteristics; and to determine the effect of packing plant, breed type, and sex class on these variables. One thousand beef carcasses were selected at three packing plants to match the breed type, sex class, marbling score, dark-cutting discount, overall maturity, carcass weight, and yield grade distributions reported for the U.S. beef carcass population by the 1995 National Beef Quality Audit. Data collected on these carcasses included USDA quality and yield grade data and measurements of muscle color (L*, a*, b*), muscle pH, and electrical impedance of the longissimus muscle. About one-half (53.1%) of the carcasses fell within a muscle pH range of 5.40 to 5.49, and 81.3% of the carcasses fell within a longissimus muscle pH range of 5.40 to 5.59. A longissimus muscle pH of 5.87 was the approximate cut-off between normal and dark-cutting carcasses. Frequency distributions indicated that L* values were normally distributed, whereas a* and b* values were abnormally distributed (skewed because of a longer tail for lower values, a tail corresponding with dark-cutting carcasses). Electrical impedance was highly variable among carcasses but was not highly related to any other variable measured. Color measurements (L*, a*, b*) were correlated (P < 0.05) with lean maturity score (-.58, -.31, and -.43, respectively) and with muscle pH (-.40, -.58, and -.56, respectively). In addition, fat thickness was correlated with muscle pH and color (P < 0.05). There was a threshold at approximately . 76 cm fat thickness, below which carcasses had higher muscle pH values and lower colorimeter readings. Steer carcasses (L* = 39.62, a* = 25.20, and b* = 11.03) had slightly higher colorimeter readings (P < 0.05) than heifer carcasses (L* = 39.20, a* = 24.78, and b* = 10.80) even though muscle pH was not different between steer and heifer carcasses. Dairy-type carcasses (pH = 5.59, L* = 37.56, a* = 23.40, and b* = 9.68) had higher muscle pH values and lower colorimeter readings than either native-type (pH = 5.50, L* = 39.55, a* = 25.13, and b* = 11.00) or Brahman-type (pH = 5.46, L* = 39.75, a* = 25.17, and b* = 11.05) carcasses (P < 0.05).