Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Molecular Characterization of Human Placental Mesenchymal Stem Cells from Human Aborted Fetal Tissue as a Model to Study Mechanism of Spontaneous Abortion

Mesenchymal stem cells (MSCs) have become an important component in stem cell therapies and can be isolated from various adult tissues. The human placenta is a fetomaternal organ having a high population of multipotent stem cells with better plasticity and differential potential. It is interesting to see the molecular phenotypes of these stem cells in placenta obtained from aborted fetus to understand the mechanism of spontaneous abortion. In the present study, we have proposed to isolate multipotent stem cells from human aborted placental tissue and characterized them by using molecular and morphological analysis. Our study has shown that the placenta derived Mesenchymal stem cells (hPMSCs) have elongated epithelioid like morphology and showed high pluripotency potential by expressing Oct4, Nanog and Sox2 along with expression of Mesenchymal, hematopoietic, cytokine and chemokine markers. We have further shown that hPMSCs cells have the capacity for spontaneous differentiation into cardiomyocytes and osteocytes which have confirmed the expression of specific cardiac and osteogenic markers. Interestingly, this study has clearly shown that there is an abnormal expression of CD 73, CD 100, CD 45, Ki67 and Vimentin in aborted fetal tissue thus indicates some role of these genes in the maintenance of pregnancies. Thus, this study concludes that hPMSCs cells can be used as an in vitro model system for the evaluation of the mechanism of spontaneous abortion. Similarly, due to their multipotent characteristic they can be used for future regenerative therapies for various disorders.
Dynamic Aberration-corrected STEM of Bimetallic Nanocatalysts during Surface Diffusion

Fundamental investigations of catalyst structures and the mechanisms of catalytic reactions requires characterization imaging of surfaces at the atomic scale and probing the structures and energetics of the reacting molecules as they function under reaction condition on varying time and length scales. Highangle annular dark field (HAADF) STEM is an indispensable technique for analyzing heterogeneous catalysts, in particular those comprising high atomic number (Z) metallic nanoparticles (NPs) dispersed on low-Z supports [1]. Readily interpretable atomic-scale Z-contrast imaging with high spatial resolution spectroscopy, including X-ray energy dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS), allows researchers to investigate structural information such as dimensions, morphologies, and size distribution of catalytic NPs as well as their material chemistry (e.g., chemical composition, bonding of catalytic particles with supports at interface, etc.).
Chronic interstitial nephritis in agricultural communities: a worldwide epidemic with social, occupational and environmental determinants

Abstract Increase in the prevalence of chronic kidney disease (CKD) is observed in Central America, Sri Lanka and other tropical countries. It is named chronic interstitial nephritis in agricultural communities (CINAC). CINAC is defined as a form of CKD that affects mainly young men, occasionally women. Its aetiology is not linked to diabetes, hypertension, glomerulopathies or other known causes. CINAC patients live and work in poor agricultural communities located in CINAC endemic areas with a hot tropical climate, and are exposed to toxic agrochemicals through work, by ingestion of contaminated food and water, or by inhalation. The disease is characterized by low or absent proteinuria, small kidneys with irregular contours in CKD stages 3‐4 presenting tubulo‐interstitial lesions and glomerulosclerosis at renal biopsy. Although the aetiology of CINAC is unclear, it appears to be multifactorial. Two hypotheses emphasizing different primary triggers have been proposed: one related to toxic exposures in the agricultural communities, the other related to heat stress with repeated episodes of dehydration heath stress and dehydration. Existing evidence supports occupational and environmental toxins as the primary trigger. The heat stress and dehydration hypothesis, however, cannot explain: why the incidence of CINAC went up along with increasing mechanization of paddy farming in the 1990s; the non‐existence of CINAC in hotter northern Sri Lanka, Cuba and Myanmar where agrochemicals are sparsely used; the mosaic geographical pattern in CINAC endemic areas; the presence of CINAC among women, children and adolescents who are not exposed to the harsh working conditions; and the observed extra renal manifestations of CINAC. This indicates that heat stress and dehydration may be a contributory or even a necessary risk factor, but which is not able to cause CINAC by itself.
Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist of the Type I Interferon-Induced Antiviral State

ABSTRACT Type I interferons (IFNs) induce expression of more than 300 cellular genes that provide protection against viruses and other pathogens. For survival, viruses evolved defenses to prevent the IFN response or counteract the IFN-induced antiviral state. However, because viruses and cells coevolved, the dynamic relationship between virus and host is difficult to discern. In the present study, we demonstrated that vaccinia virus with a large deletion near the left end of the genome had a diminished ability to replicate in cells that had been pretreated with beta interferon (IFN-β), suggesting that one or more of the missing 17 open reading frames (ORFs) encode an antagonist of the IFN-induced antiviral state. By systematically deleting groups of ORFs and then individual ORFs, the C9L gene was shown to be required for IFN resistance. Replication of the C9L deletion mutant (vΔC9) was impaired in human cells that had been pretreated with IFN-β. Expression of viral early genes occurred, but subsequent events, including genome uncoating, genome replication, and postreplicative gene expression, were inhibited. Expression of the C9 protein occurred prior to genome replication, consistent with an early role in counteracting the IFN-induced antiviral state. C9 contains six ankyrin repeat motifs and a near C-terminal F-box. Mass spectrometry and immunoblotting identified host proteins that copurified with a functional epitope-tagged C9. The most abundant proteins were components of the SCF (CUL1, SKP1, F-box) and signalosome/deneddylation complexes, which interact with each other, suggesting a possible role in proteolysis of one or more interferon-induced proteins. IMPORTANCE Poxviruses comprise a family of large DNA viruses that replicate in the cytoplasm of vertebrate and insect hosts and cause human and zoonotic diseases. In most cases the primary infection is moderated by innate immune defenses. Vertebrates, including fish, amphibians, reptiles, birds, and mammals, all produce type I interferon homologs. In humans, interferon stimulates the synthesis of more than 300 proteins thought to have roles in host defense. Conversely, viruses have evolved means to thwart the host defenses. We are attempting to deconstruct the established virus-host relationship in order to better understand the molecular mechanisms involved. In the present study, we identified a vaccinia virus gene that prevents interferon-mediated inhibition of very early stages of viral replication and is conserved in orthopoxviruses. The viral protein was shown to interact with host proteins involved in proteolysis, suggesting that vaccinia virus may subvert the cellular apparatus for its own defense.
Standardless Quantification at Trace Elemental (PPM) Levels Using a Novel Attachment within an Electron Microscope and Microprobe

Despite significant advances in quantitative compositional mapping using electron microscopy based techniques (e.g. SEM-EDS and EPMA), the vast majority of analyses are performed standardless [1], which can lead to systematic errors that limit the accuracy of the results [2]. Here we present a newly developed x-ray illumination beam attachment developed to enable complementary, parts-per-million sensitivity at microns-scale resolution. The attachment will provide 10 to 1000-fold improvement in detection limit, and can be used to supplement standard-less electron-induced fluorescence information. The Sigray FAAST-SEM™ attachment relies on several key innovations, including: (1) a revolutionary, patent-pending new type of high flux x-ray source designed to be >10X brighter than the brightest rotating anode x-ray source currently available; and (2) an x-ray mirror lens with high spatial resolution, high focusing efficiency, and large working distances designed to accommodate the geometries of existing SEM chambers. Over existing commercial micro x-ray fluorescence (µXRF) attachments, the system provides 300-500X speed to provide equivalent trace elemental mapping within minutes rather than hours or days for conventional approaches. Moreover, the system resolution is designed to have resolution comparable to electron-based fluorescence spot sizes for correlative measurements. A major design consideration for the illumination beam system was optimizing the quantification capabilities through careful selection of the x-ray focusing optic to be used. X-rays intrinsically provide high fidelity for compositional analysis, as photons do not encounter the same “bloom” effect as particle-based (e.g. electron-based) microanalysis and produce fluorescence from only the illuminated spot at the sample. However, current approaches to x-ray optics are primarily through use of polycapillary x-ray optics, which concentrate x-rays of various energies into illumination spots of differing sizes at the sample. This results
“Big Data” and the Electronic Health Record

Summary Objectives: Implementation of Electronic Health Record (EHR) systems continues to expand. The massive number of patient encounters results in high amounts of stored data. Transforming clinical data into knowledge to improve patient care has been the goal of biomedical informatics professionals for many decades, and this work is now increasingly recognized outside our field. In reviewing the literature for the past three years, we focus on “big data” in the context of EHR systems and we report on some examples of how secondary use of data has been put into practice. Methods: We searched PubMed database for articles from January 1, 2011 to November 1, 2013. We initiated the search with keywords related to “big data” and EHR. We identified relevant articles and additional keywords from the retrieved articles were added. Based on the new keywords, more articles were retrieved and we manually narrowed down the set utilizing predefined inclusion and exclusion criteria. Results: Our final review includes articles categorized into the themes of data mining (pharmacovigilance, phenotyping, natural language processing), data application and integration (clinical decision support, personal monitoring, social media), and privacy and security. Conclusion: The increasing adoption of EHR systems worldwide makes it possible to capture large amounts of clinical data. There is an increasing number of articles addressing the theme of “big data”, and the concepts associated with these articles vary. The next step is to transform healthcare big data into actionable knowledge.
SOLID DISPERSION: A FRUITFUL APPROACH FOR IMPROVING THE SOLUBILITY AND DISSOLUTION RATE OF POORLY SOLUBLE DRUGS

In recent years, the formulation of poorly soluble compounds presented interesting challenges for formulation scientists in the pharmaceutical industry. Up to 40% of new chemical entities discovered by the pharmaceutical industry are poorly soluble or lipophilic compounds, which lead to poor oral bioavailability, high intra and inter subject variability and lack of dose proportionality. This frequently results in potentially important products not reaching the market or not achieving their full potential. Poorly water-soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Improvement in the extent and rate of dissolution is highly desirable for such compounds, as this can lead to an increased and more reproducible oral bioavailability and subsequently to clinically relevant dose reduction and more reliable therapy. The enhancement of dissolution rate and oral bioavailability is one of the greatest challenges in the development of poorly water soluble drugs. Experience with solid dispersions over the last 20-30 years indicates that this is a very fruitful approach to improving the solubility, dissolution rates and consequently the bioavailability of poorly soluble drugs. Solid dispersion is used to produce a homogeneous distribution of a small amount of drug in solid state. This article summarize some of the practical aspects for the preparation of solid dispersion like selection of carrier ,method of physicochemical characterization, their advantages, limitations and applications along with an insight into the molecular arrangement of drug in solid dispersion. Solid dispersion technique is a very useful method for pharmaceutical point of view because of its capability to solve the solubility problems by using solid dispersion method. Key words: Solid dispersion, solubility, dissolution, selection of carriers
Neonatal Overnutrition Increases Testicular Size and Expression of Luteinizing Hormone β-Subunit in Peripubertal Male Rats

Proper nutrition is important for growth and development. Maturation of the reproductive axis and the timing of pubertal onset can be delayed when insufficient nutrition is available, or possibly advanced with nutritional abundance. The childhood obesity epidemic has been linked to a secular trend in advanced puberty in some populations. The increase in circulating leptin that occurs in association with obesity has been suggested to act as a signal that an adequate nutritional status exists for puberty to occur, allowing activation of central mechanisms. However, obesity-associated hyperleptinemia is linked to decreased leptin sensitivity, at least in adults. Here, we analyzed whether neonatal overnutrition modifies the response to an increase in leptin in peripubertal male rats, as previously demonstrated in females. Wistar rats were raised in litters of 4 (neonatal overnutrition) or 12 pups (controls) per dam. Leptin was administered sc (3 µg/g body weight) at postnatal day 35 and the rats killed 45 min or 2 h later. Postnatal overfeeding resulted in increased body weight and circulating leptin levels; however, we found no overweight-related changes in the mRNA levels of neuropeptides involved in metabolism or reproduction. In contrast, pituitary expression of luteinizing hormone (LH) beta-subunit was increased in overweight rats, as was testicular weight. There were no basal differences between L4 and L12 males or in their response to leptin administration in pSTAT3 levels in the hypothalamus at either 45 min or 2 h. In contrast, pJAK2 was found to be higher at 45 min in L4 compared to L12 males regardless of leptin treatment, while at 2 h it was higher in L4 leptin-treated males compared to L12 leptin-treated males, as well as L4 vehicle-treated rats. There were no changes in response to leptin administration in the expression of the neuropeptides analyzed. However, serum LH levels rose only in L4 males in response to leptin, but with no change in testosterone levels. In conclusion, the advancement in pubertal onset in males with neonatal overnutrition does not appear to be related to overt modifications in the central response to exogenous leptin during the peripubertal period.
Discontinuation due to adverse events in randomized trials of orlistat, sibutramine and rimonabant: a meta‐analysis

The objective of this article was to estimate the risk of discontinuation due to adverse events in trials of orlistat, sibutramine and rimonabant. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles were searched from 1990 to May 2008. All randomized placebo‐controlled trials of 12–24 months of duration on adults using licensed doses were included. Studies/study arms were excluded if they evaluated weight maintenance after weight loss. Trials were identified, subjected to inclusion and exclusion criteria and reviewed. Data on participants, interventions and discontinuation were extracted and trials rated for quality based on established criteria. A random effects model was used to estimate pooled risk ratios, risk differences and number needed to harm (NNH). A total of 28 trials met the inclusion criteria (16 orlistat, 7 sibutramine and 5 rimonabant). The risk ratios for discontinuation due to adverse events were significantly elevated for rimonabant (2.00; 1.66–2.41) and orlistat (1.59; 1.21–2.08), but not sibutramine (0.98, 0.68–1.41). Compared with placebo, the risk difference was the largest for rimonabant (7%, 5–9%; NNH 14, 11–19), followed by orlistat (3%, 1–4%; NNH 39, 25–83), while no significant difference was seen for sibutramine (0.2%, −3 to 4%; NNH 500). The most common adverse events leading to withdrawal were gastrointestinal for orlistat (40%) and psychiatric for rimonabant (47%). Corresponding information was unavailable for sibutramine. In conclusion, available weight loss drugs differ markedly regarding risk of discontinuation due to adverse events, as well as in underlying causes of these events. Given the large number of patients eligible for treatment, the low NNH for rimonabant is a concern.
Design and Fabrication of a Stretchable Circuit Board for Wireless Posture Measurement

We introduce a novel fabrication of a stretchable circuit based on a polydimethylsiloxane (PDMS) substrate for wireless posture measurement. To prevent the typical emergence of cracks attributed to thermal mismatch between the metal seed layer and the PDMS substrate, an intermittent process is proposed to deposit a metal seed layer directly on a PDMS substrate. Afterward, the resistance of the S-shape Cu-wire in the stretchable circuit was measured at different strain states. Results showed that the resistance of a Cu-wire within 55 mm<inline-formula> <tex-math notation="LaTeX">$\times 0.2$ </tex-math></inline-formula> mm<inline-formula> <tex-math notation="LaTeX">$\times 0.012$ </tex-math></inline-formula> mm increased not more than <inline-formula> <tex-math notation="LaTeX">$0.060~\Omega $ </tex-math></inline-formula> at 30% strain from 0.735 <inline-formula> <tex-math notation="LaTeX">$\Omega $ </tex-math></inline-formula> at zero strain. Finally, the wireless posture measurement system was verified through body posture experiments.
Fundamental biofuel characteristics impacting coal-biomass cofiring

Biofuels include wood and wood wastes, various crop wastes (e.g. alfalfa stems, rice hulls, bagasse), and lignocellulosic materials grown specifically for energy generation. These fuels exhibit distinct characteristics as a function of their anatomy, physical properties, and chemical composition. These characteristics include specific gravity, porosity (or void volume), volatility, heat content, and ash chemistry. Because the biofuels are derived from living plant matter, they are fibrous, modest in specific gravity (typically 0.3 - 0.6 on an oven dry basis), and quite porous. The porosity, along with the fact that these are materials originally grown as crops (including trees), leads to the potential for high moisture content. Chemically, these are very reactive materials with high volatile/fixed carbon ratios. Typically they contain little nitrogen and virtually no sulfur. The heating value is commonly on the order of 4,170 - 5,280 cal/g (7,500 - 9,500 Btu/lb). Ash contents can range from 10% depending upon the type of biofuel being utilized. The ash is typically very alkaline (base/acid ratios in the range of 0.5 -6.0). Alkalinity is influenced by soil conditions, fertilizer applications during growth, and consequent mineral uptake. Heavy metal concentrations in the biofuels are typically low, although they are influencedmore » by the environment existing at the time when the biomass is grown. As a consequence, biofuels behave in ways that are fundamentally different from the various types of coal and lignite. This paper reviews the characteristics of biofuels in relation to coal; and it then considers the consequences of biofuel characteristics to the process of cofiring biomass in pulverized coal and cyclone boilers. The paper concludes with comment on the impact of biofuel characteristics on coal-fired power plant performance with emphasis on boiler efficiency and fossil fired generation economics. « less
Strategies for CLEM Imaging.

Correlative Light and Electron Microscopy (CLEM) is a technique with many variations. The premise of the technique is to link events observable by fluorescence in cell biology and physiology with the higher resolution morphology and structure obtained by cryo TEM[1]. Thus once static snapshots from TEM now have a dynamic range. Our lab has developed strategies for correlating various biological systems for the CLEM imaging workflow[2]. We have developed a range of protocols for imaging labeled vs. unlabeled whole cells, locating labeled and expressed proteins within cells, transfected nanoprobes within cells, labeled phage attaching to bacteria, and virus attaching to and being taken up by cells. Each of these scenarios requires an adaptation to the sample preparation. In each case, the experiment needs to be designed such that it is compatible with plunge-freezing of the sample. A factor to consider is how the cells of interest will be adhered to the TEM grid. Some eukaryotic cells grow fine on carbon support films, while others require pre-coating of the film with substrates such as collagen or fibrinogen. Another factor is timing of application of transfection agent and potential washing steps. We then vitrify the cells on grids with either a Cryoplunge3 (Gatan) or a Vitrobot Mark III (FEI). Choice of blotting method also depends on the type and thickness of the cells of interest. Cryo fluorescence imaging (cryofLM) is done on a Leica cryo CLEM system (Leica Microsystems) with a 50 X ceramic objective (N/A=0.90)[3,4]. Areas of interest are mapped as multi-channel z-stacks using LAS X matrix screener software (Leica Microsystems). Coordinates of regions of interest within this grid map can be saved and then the map and coordinates are transferred to the JEOL JEM-2200FS 200 kV field emission TEM (JEOL, Ltd., Japan) equipped with an in-column Omega energy filter. Using the SerialEM software package [5] the fluorescence map and coordinates are imported and registered to the cryoTEM low magnification grid map of the same grid. From here the area of interest can by imaged at an intermediate magnification with SerialEM’s montage option for morphological information, followed by higher magnification imaging or tomography.