Miracle-dz/UniFAR-FTUs huggingface dataset:
Microflare heating of the galactic halo

Recent estimates of the strength of the random component of the galactic magnetic field suggest that magnetic reconnection is probably important in heating the galactic halo. A microflare model of impulsive energy release has been proposed for the solar corona by Sturrock et al. (1990, ApJ, 356). When the solar microflare model is scaled to a heating rate and pressure appropriate to the galactic halo, it predicts soft X-ray background emission, column densities of highly ionized species, and diffuse UV line emission in reasonable agreement with observed values. Column densities and surface brightnesses of low-ionization species are more ambiguously predicted by the model, but magnetic heating could contribute to them as well
Predictive Maintenance by Electrical Signature Analysis to Induction Motors

Industries always try to increase the reliability of their productive process. In this context, predictive maintenance performs a fundamental role in order to reach high availability and reliability concerning their pieces of equipment. Predictive maintenance can be understood as the action on the equipment, system or installations based on the previous knowledge about the operation condition or performance, obtained by means of parameters previously determined (Bonaldi et al, 2007).
Time for an Open Dialogue on the Issue of Enthusiasm to Translate Stem Cells to Patients

Copyright: © 2012 Rameshwar P. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The past decade has seen an `explosion’ on the numbers of papers, journals and scientific meetings focused on stem cell. These efforts, although seemed much, continue appropriately and have led to clinical trials. Admixed with the knowledge that further research studies are needed prior to clinical trials are those who show over-enthusiasm. The latter group, unknowingly, include patients, physicians and scientists, all of are willing to circumvent the available and common-sense ethical guidelines.
Familial idiopathic interstitial pneumonia: histopathology and survival in 30 patients.

CONTEXT Familial idiopathic interstitial pneumonia (F-IIP) describes the unexplained occurrence of diffuse parenchymal lung disease in related individuals. Prevailing wisdom suggests that the histopathology of F-IIP is indistinguishable from that of idiopathic pulmonary fibrosis, namely, usual interstitial pneumonia (UIP). OBJECTIVE To define the histopathology of F-IIP in lung tissue samples. DESIGN Tissue sections from 30 patients with F-IIP, enrolled in a national research program, were evaluated by 3 pulmonary pathologists using 15 predefined histopathologic features. Each feature was recorded independently before a final diagnosis was chosen from a limited list dichotomized between UIP or "not UIP. " These 2 groups were then compared to survival. RESULTS The consensus diagnosis for the F-IIP cohort was an unclassifiable parenchymal fibrosis (60%), with a high incidence of histopathologic honeycombing, fibroblast foci, and smooth muscle in fibrosis. Usual interstitial pneumonia, strictly defined, was identified in less than half of the F-IIP cases (range, 23%-50%). Interobserver agreement was fair (κ = 0.37) for 2 observers for the overall diagnosis of UIP. Findings unexpected in UIP were prevalent. The survival for the entire F-IIP cohort was poor, with an estimated mortality of 93% and a median age at death of 60.9 years. Subjects with UIP had a shorter survival and younger age at death. CONCLUSIONS Pulmonary fibrosis was the dominant histopathology identified in our patients, but diagnostic features of UIP were seen in less than 50% of the samples. Overall survival was poor, with mortality accelerated apparently by the presence of a UIP pattern of disease.
Differential diagnosis of renal tumors with clear cytoplasm: clinical relevance of renal tumor subclassification in the era of targeted therapies and personalized medicine.

CONTEXT The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and-with the exception of some rare tumors-the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. OBJECTIVE To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. DATA SOURCES Published literature and personal experience. CONCLUSIONS In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.
Pharmacokinetics and pharmacodynamics of antimicrobial drugs

Background: Antimicrobial drugs exhibit different characteristics in their correlation between antimicrobial drug concentrations and effects on microorganisms. These correlations have been studied using different approaches including in vitro analyses with constant and fluctuating concentrations and in vivo analyses involving animals and humans. Mathematical analysis includes correlation of pharmacokinetic-pharmacodynamic (PK-PD) indices to an outcome parameter. Further insight can be gained by mechanism-based modelling of antimicrobial drug effects. Methods and results: This review aims to provide an overview on the various approaches used to analyse antimicrobial pharmacodynamics, to discuss the limitations of these approaches, to indicate recent developments and to summarise the current knowledge on PK-PD target values as derived from human studies. Conclusion: It is expected that PK-PD analysis of antimicrobial drug effects will lead to a more efficient and possibly also less toxic antimicrobial drug therapy.
Blood Flow Distribution in the Human Leg Following Epidural Sympathetic Blockade

Blood flow in the anterior tibial skeletal muscle group and skin temperature of the foot were measured before and after epidural sympathetic nerve blockade in 8 patients with no evidence of arterial insufficiency, and in 17 patients with obliterative arterial disease of the lower limb. Muscle blood flow was calculated from the clearance of locally injected xenon Xe 133 in order to measure tissue nutritional blood flow only. Resting muscle blood flow was significantly reduced, and skin temperature of the foot significantly increased after sympathetic block in both groups of patients. It is suggested that the intense skin vasodilation due to the release of vasoconstrictor tone causes redistribution of total limb blood flow with a reduction of the blood flow to muscle which has low metabolic requirements at rest.
Physical Activity and Fitness in African Americans: Implications for Cardiovascular Health

The prevalence of cardiovascular disease (CVD), obesity, diabetes mellitus, hypertension, and physical inactivity is significantly higher in African Americans. The higher prevalence of these important risk factors is thought to be largely responsible for the higher CVD mortality rate in blacks. Limited evidence suggests that the aerobic power of African Americans may be inherently lower than that of whites. This apparent deficiency may be explained, in part, by differences in muscle oxidative capacity but is poorly understood. Studies have shown a lower prevalence of overweight/obesity, the metabolic syndrome, and insulin resistance with higher levels of physical activity/fitness. Training studies have shown that increasing physical activity and/or fitness positively affects metabolic risk factors, body composition, and insulin sensitivity. The few studies of African Americans suggest that they respond to exercise training in a manner similar to whites. Controlling blood pressure of hypertensive blacks at levels comparable with that of whites could result in more than 7000 fewer deaths from CVD. Physical fitness has been shown to be negatively associated with blood pressure in African Americans, but results from interventional studies have been equivocal. Some evidence suggests that increased physical activity and/or fitness may reduce the blood pressure response to submaximal exercise and other stressors in African Americans. Blacks have higher levels of high-density lipoprotein cholesterol (HDL-C) and lower levels of total cholesterol, triglycerides, and small dense low-density lipoprotein particles. Studies suggest that the blood lipid response to exercise training is similar between African Americans and whites. There may be an intensity threshold of 75% of age-predicted maximal heart rate to elicit significant changes in HDL-C. More research is needed to explore the association between physical activity/fitness and CVD risk factors in this population.
Épidémie de sida en Afrique subsaharienne

Les connaissances utiles a la lutte contre le virus de l’immunideficience humaine (VIH) et le sida en Afrique subsaharienne ne sont pas toutes extrapolables a partir des donnees issues des pays industrialises. Cet article tente de passer en revue les specificites de l’epidemie africaine en termes d’epidemiologie, d’histoire naturelle, d’interventions therapeutiques validees et de questions restant a explorer. Loin d’etre demunis d’outils efficaces et de pistes de recherches pour lutter contre ce fleau qui decime un continent, nous sommes aujourd’hui avant tout confrontes a un deficit de mobilisation et de moyens.
Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.

CONTEXT - Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various cancers and reveal a new era of cancer immunotherapy. OBJECTIVE - To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression. DATA SOURCES - Representative medical literature regarding PD-L1 expression in various cancers, including the preliminary results of the Blue Proposal, which compares different immunohistochemical stains for PD-L1 reported in the recent American Association of Cancer Research (AACR) Annual Meeting (April 16-20, 2016). CONCLUSION - Either PD-1/PD-L1-targeted therapy alone or in combination with other treatment modalities provides benefit for patients with advanced cancers. Because of the complexity of cancer immunity, we still do not have a reliable biomarker to predict the response of PD-1/PD-L1-targeted therapy. Future studies, including methods beyond immunohistochemical stains, are needed to develop reliable biomarker/biomarkers for pathology laboratories to aid in selecting patients who will benefit most from PD-1/PD-L1-targeted therapy.
Concise Review: Clinical Translation of Wound Healing Therapies Based on Mesenchymal Stem Cells

There is enormous worldwide demand for therapies to promote the efficient resolution of hard‐to‐heal wounds with minimal appearance of scarring. Recent in vitro studies with mesenchymal stem cells (MSCs) have identified numerous mechanisms by which these cells can promote the process of wound healing, and there is significant interest in the clinical translation of an MSC‐based therapy to promote dermal regeneration. This review provides a systematic analysis of recent preclinical and clinical research to evaluate the use of MSCs in wound healing applications. These in vivo studies provide overwhelming evidence that MSCs can accelerate wound closure by modulating the inflammatory environment, promoting the formation of a well‐vascularized granulation matrix, encouraging the migration of keratinocytes, and inhibiting apoptosis of wound healing cells. The trophic effects of MSC therapy also appear to augment wound healing in diabetic tissues, thereby preventing the formation of nonhealing ulcers. Finally, a number of delivery systems have been evaluated and indicate that MSCs could be the basis of a versatile therapy to fulfill the clinical needs for dermal regeneration. However, despite the apparent advantages of MSC‐based therapies, there have been only limited clinical investigations of this type of therapy in humans. Thus, our review concludes with a discussion of the translational barriers that are limiting the widespread clinical use of MSCs to enhance wound healing.
Modeling and Rescue of the Vascular Phenotype of Williams‐Beuren Syndrome in Patient Induced Pluripotent Stem Cells

Elastin haploinsufficiency in Williams‐Beuren syndrome (WBS) leads to increased vascular smooth muscle cell (SMC) proliferation and stenoses. Our objective was to generate a human induced pluripotent stem (hiPS) cell model for in vitro assessment of the WBS phenotype and to test the ability of candidate agents to rescue the phenotype. hiPS cells were reprogrammed from skin fibroblasts of a WBS patient with aortic and pulmonary stenosis and healthy control BJ fibroblasts using four‐factor retrovirus reprogramming and were differentiated into SMCs. Differentiated SMCs were treated with synthetic elastin‐binding protein ligand 2 (EBPL2) (20 μg/ml) or the antiproliferative drug rapamycin (100 nM) for 5 days. We generated four WBS induced pluripotent stem (iPS) cell lines that expressed pluripotency genes and differentiated into all three germ layers. Directed differentiation of BJ iPS cells yielded an 85%–92% pure SMC population that expressed differentiated SMC markers, were functionally contractile, and formed tube‐like structures on three‐dimensional gel assay. Unlike BJ iPS cells, WBS iPS cells generated immature SMCs that were highly proliferative, showed lower expression of differentiated SMC markers, reduced response to the vasoactive agonists, carbachol and endothelin‐1, impaired vascular tube formation, and reduced calcium flux. EBPL2 partially rescued and rapamycin fully rescued the abnormal SMC phenotype by decreasing the smooth muscle proliferation rate and enhancing differentiation and tube formation. WBS iPS cell‐derived SMCs demonstrate an immature proliferative phenotype with reduced functional and contractile properties, thereby recapitulating the human disease phenotype. The ability of rapamycin to rescue the phenotype provides an attractive therapeutic candidate for patients with WBS and vascular stenoses.
Long‐Term Maintenance of Limbal Epithelial Progenitor Cells Using Rho Kinase Inhibitor and Keratinocyte Growth Factor

Corneal epithelial stem cells are located in the limbus, the junction between the cornea and the conjunctiva. A limbal epithelium model in vitro would be useful for the study of epithelial stem cells, as well as improving the quality of cultivated epithelial sheets for the treatment of limbal stem cell deficiency. In this study, we succeeded in constructing a limbal epithelium‐like structure that could be maintained for at least 5 months in vitro. We modified conventional medium by replacing epidermal growth factor with keratinocyte growth factor (KGF) and adding Y‐27632, a rho kinase inhibitor. Using this medium, epithelial cells freshly isolated from human limbus were cocultured with human mesenchymal stem cell‐derived feeder cells. Cells formed a stratified layer without air exposure, and both basal and suprabasal layers maintained their unique morphologies for up to 5 months. Basal layers expressed the progenitor marker p63 uniformly and K15 heterogeneously. Expressions of PAX6, K3, and K12 indicated that cell sheets underwent normal differentiation in the corneal epithelium lineage. Although medium was changed daily after day 7, cell debris was observed every day, suggesting that cell sheets underwent turnover. Furthermore, secondary colonies were observed from cells dissociated from 1‐month and 3‐month cultured sheets. In conclusion, human limbal epithelial cell sheet cultures with KGF and Y‐27632 maintained stratification, high expression of both stem/progenitor markers and differentiation markers, and colony‐forming cells long‐term. This protocol may be useful as an in vitro limbal epithelial model for basic studies.
Concise Review: Growth Differentiation Factor 15 in Pathology: A Clinical Role?

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor β family discovered in a broad range of cells, as indicated by the diversity of its nomenclature. However, the only tissue that expresses a high amount of GDF15 in the physiologic state is placenta. GDF15 is easily detected in blood, and its concentration varies with age. In fact, increased blood concentration of GDF15 is associated with numerous pathological conditions. However, the biological significance underlying these observations is far from clear. GDF15 could have a positive or negative role depending on the state of cells or their environment. Furthermore, study of its biology is hampered by lack of knowledge of its receptor and thus the signaling pathways that drive its action. GDF15 seems to be an integrative signal in pathologic conditions, giving information on severity of disease. Its effectiveness in classifying patients to modulate treatment remains to be shown. Development of therapeutic interventions with GDF15 or anti‐GDF15 agents remains difficult until we uncover the mechanism that drives its activity.
Embryonic Stem Cells / Induced Pluripotent Stem ( iPS ) Cells Concise Review : Parthenote Stem Cells for Regenerative Medicine : Genetic , Epigenetic , and Developmental Features

Embryonic stem cells (ESCs) have the potential to provide unlimited cells and tissues for regenerative medicine. ESCs derived from fertilized embryos, however, will most likely be rejected by a patient’s immune systemunless appropriately immunomatched. Pluripotent stemcells (PSCs) genetically identical to a patient can nowbe established by reprogramming of somatic cells. However, practical applications of PSCs for personalized therapies are projected to be unfeasible because of the enormous cost and time required to produce clinical-grade cells for each patient. ESCs derived from parthenogenetic embryos (pESCs) that are homozygous for human leukocyte antigens may serve as an attractive alternative for immunomatched therapies for a large population of patients. In this study, we describe the biology and genetic nature of mammalian parthenogenesis and review potential advantages and limitations of pESCs for cell-based therapies. STEMCELLS TRANSLATIONALMEDICINE 2014; 3:290–298
Human Perivascular Stem Cell‐Based Bone Graft Substitute Induces Rat Spinal Fusion

Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), isolated by fluorescence‐activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample‐matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose‐dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC‐treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC‐based products show promise for future efforts in clinical bone regeneration and repair.
Differentiation of Human Limbal‐Derived Induced Pluripotent Stem Cells Into Limbal‐Like Epithelium

Limbal epithelial stem cell (LESC) deficiency (LSCD) leads to corneal abnormalities resulting in compromised vision and blindness. LSCD can be potentially treated by transplantation of appropriate cells, which should be easily expandable and bankable. Induced pluripotent stem cells (iPSCs) are a promising source of transplantable LESCs. The purpose of this study was to generate human iPSCs and direct them to limbal differentiation by maintaining them on natural substrata mimicking the native LESC niche, including feederless denuded human amniotic membrane (HAM) and de‐epithelialized corneas. These iPSCs were generated with nonintegrating vectors from human primary limbal epithelial cells. This choice of parent cells was supposed to enhance limbal cell differentiation from iPSCs by partial retention of parental epigenetic signatures in iPSCs. When the gene methylation patterns were compared in iPSCs to parental LESCs using Illumina global methylation arrays, limbal‐derived iPSCs had fewer unique methylation changes than fibroblast‐derived iPSCs, suggesting retention of epigenetic memory during reprogramming. Limbal iPSCs cultured for 2 weeks on HAM developed markedly higher expression of putative LESC markers ABCG2, ΔNp63α, keratins 14, 15, and 17, N‐cadherin, and TrkA than did fibroblast iPSCs. On HAM culture, the methylation profiles of select limbal iPSC genes (including NTRK1, coding for TrkA protein) became closer to the parental cells, but fibroblast iPSCs remained closer to parental fibroblasts. On denuded air‐lifted corneas, limbal iPSCs even upregulated differentiated corneal keratins 3 and 12. These data emphasize the importance of the natural niche and limbal tissue of origin in generating iPSCs as a LESC source with translational potential for LSCD treatment.