Miracle-dz/UniFAR-FTUs huggingface dataset:
Hematopoietic Development from Human Induced Pluripotent Stem Cells

A decade of research on human embryonic stem cells (ESC) has paved the way for the discovery of alternative approaches to generating pluripotent stem cells. Combinatorial overexpression of a limited number of proteins linked to pluripotency in ESC was recently found to reprogram differentiated somatic cells back to a pluripotent state, enabling the derivation of isogenic (patient‐specific) pluripotent stem cell lines. Current research is focusing on improving reprogramming protocols (e.g., circumventing the use of retroviral technology and oncoproteins), and on methods for differentiation into transplantable tissues of interest. In mouse ESC, we have previously shown that the embryonic morphogens BMP4 and Wnt3a direct blood formation via activation of Cdx and Hox genes. Ectopic expression of Cdx4 and HoxB4 enables the generation of mouse ESC‐derived hematopoietic stem cells (HSC) capable of multilineage reconstitution of lethally irradiated adult mice. Here, we explore hematopoietic development from human induced pluripotent stem (iPS) cells generated in our laboratory. Our data show robust differentiation of iPS cells to mesoderm and to blood lineages, as shown by generation of CD34+CD45+ cells, hematopoietic colony activity, and gene expression data, and suggest conservation of blood patterning pathways between mouse and human hematopoietic development.
Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors.

BACKGROUND Local anesthetics were suggested to have a potential for neurotoxicity in both clinical reports and laboratory experiments. Growing neurons have been shown to be susceptible to the toxic effects of local anesthetics in culture. These findings have generated the interest in factors that would rescue the neurons affected by the neurotoxicity of local anesthetics. METHODS Primary cultured dorsal root ganglia were isolated from age-matched chick embryos and exposed to lidocaine. After 60 min of exposure, the culture media were replaced to wash out the lidocaine. Neurotrophic factors (NTFs)-brain-derived neurotrophic factor, glial-derived neurotrophic factor, or neurotrophin 3-were added to the replacement media to examine the capacity of these NTFs to support the reversibility of the lidocaine-induced growth cone collapse. The growth cone collapse assay was applied a quantitative method of assessment. RESULTS When any of the three NTFs was added to the replacement media at a minimum concentration of 10 ng/ml, significantly high reversibility of the lidocaine-induced growth cone collapse was observed, especially at 48 h after washout (P < 0.05). At that time point, there was no significant difference between the values of growth cone collapse percentage in the cells that were exposed to lidocaine and supported by the NTFs after the washout, and the control cells (not exposed to lidocaine) (P > 0.05). CONCLUSION The NTFs-brain-derived neurotrophic factor, glial-derived neurotrophic factor, and neurotrophin 3-were demonstrated to support the reversibility of lidocaine-induced growth cone collapse in primary cultured sensory neurons, an effect that was concentration- and time-dependent. Because similar effects were observed after tetracaine washout, the supporting effects of NTFs may not be specific to lidocaine.
Chilling-Susceptibility of the Blue-Green Alga Anacystis nidulans: III. LIPID PHASE OF CYTOPLASMIC MEMBRANE.

The lipid phase of cytoplasmic membrane was studied by freeze-fracture electron microscopy in the chilling-susceptible blue-green alga, Anacystis nidulans. At growth temperatures, intramembrane particles were distributed at random in the fracture faces of cytoplasmic membrane, whereas, at chilling temperatures, the fracture faces were composed of particle-free and particle-containing regions. These findings indicate that lipids of the cytoplasmic membrane were in the liquid-crystalline state at the growth temperatures and in the phase-separation state at the chilling temperatures. Temperatures for the onset of phase separation were 5 and 16 degrees C in cells grown at 28 and 38 degrees C, respectively.In comparison, another blue-green alga, Anabaena variabilis, which is not susceptible to chilling, was also examined by the freeze-fracture electron microscopy. The intramembrane particles were distributed at random in the fracture faces of cytoplasmic membrane at the growth, as well as at the chilling, temperatures.The results in this and previous studies suggest that the chilling susceptibility of A. nidulans is a result of irreversible leakage of ions from the cytoplasm when the lipids of cytoplasmic membrane are in the phase-separation state at low temperatures.
Ca2+ permeable AMPA/kainate channels permit rapid injurious Ca2+ entry

&NA; Small subsets of central neurons possessing Ca2+ permeable AMPA/kainate channels can be identified by a histochemical stain based on kainate‐stimulated Co2+ uptake (Co2+(+) neurons) and are unusually vulnerable to AMPA/kainate receptor‐mediated injury. Using brief kainate exposures (which selectively destroy Co2+(+) neurons) along with kainate triggered 45Ca2+ influx measurements, we estimate kainate to cause an unusually high rate of Ca2+ influx into Co2+(+) neurons. Also, while fura‐2 Ca2+ imaging revealed low (10 &mgr;M) kainate exposures to preferentially induce intracellular free Ca2+ ([Ca2+]i) elevations in Co2+(+) neurons, intense (100 &mgr;M) kainate exposures used in the 45Ca2+ influx studies triggered comparable [Ca2+]i rises in all neurons. These findings suggest that the exceptional vulnerability of Co2+(+) neurons to AMPA/kainate receptor‐mediated injury reflects a high rate of agonist triggered Ca2+ influx, and that [Ca2+]i rises may only poorly reflect influx rate.
The effect of gait and digital flexor muscle activation on limb compliance in the forelimb of the horse Equus caballus

SUMMARY A horse's legs are compressed during the stance phase, storing and then returning elastic strain energy in spring-like muscle-tendon units. The arrangement of the muscle-tendon units around the lever-like joints means that as the leg shortens the muscle-tendon units are stretched. The forelimb anatomy means that the leg can be conceptually divided into two springs: the proximal spring, from the scapula to the elbow, and the distal spring, from the elbow to the foot. In this paper we report the results of a series of experiments testing the hypothesis that there is minimal scope for muscle contraction in either spring to adjust limb compliance. Firstly, we demonstrate that the distal, passive leg spring changes length by 127 mm (range 106-128 mm) at gallop and the proximal spring by 12 mm (9-15 mm). Secondly, we demonstrate that there is a linear relationship between limb force and metacarpo-phalangeal (MCP) joint angle that is minimally influenced by digital flexor muscle activation in vitro or as a function of gait in vivo. Finally, we determined the relationship between MCP joint angle and vertical ground-reaction force at trot and then predicted the forelimb peak vertical ground-reaction force during a 12 m s-1 gallop on a treadmill. These were 12.79 N kg-1 body mass (BM) (range 12.07-13.73 N kg-1 BM) for the lead forelimb and 15.23 N kg-1 BM (13.51-17.10 N kg-1 BM) for the non-lead forelimb.
Association of with‐no‐lysine kinase 1 and Serine/Threonine kinase 39 gene polymorphisms and haplotypes with essential hypertension in Tibetans

Tibetans have a higher essential hypertension prevalence compared with other ethnics in China. The reason might be due to their unique environmental influence, as well as genetic factor. However, limited studies focus on Tibetan genetics and its association with hypertension. The aim of this study was to investigate the association between With‐No‐Lysine (K) Kinase 1 (WNK1), Serine/Threonine kinase 39(STK39) genes variants and hypertension in the Tibetan population. 204 Tibetan hypertensive patients and 305 normotensive controls were recruited in an epidemiological survey conducted at 2 sites in the Ganzi Tibetan autonomous region. Patients were genotyped for nineteen WNK1 candidate tag single nucleotide polymorphisms (SNPs) and three STK39 SNPs, and haplotype analysis was performed. Results showed that the allele A in rs1468326 was overrepresented in hypertensive patients versus control (53.4% vs 42.9%, P < 0.05). The multivariable‐adjusted odds ratio (OR) for hypertension among CA + AA genotypes carriers was 1.60 (95% CI: 1.02–2.62, P < 0.05), and they also had a higher systolic blood pressure (136.5 ± 28.6 vs 131.7 ± 24.8 mmHg, P < 0.05). However, the TT genotype ratio in rs6749447 was lower in hypertensives (5.4% vs 10.8%, P < 0.05), and the hypertension risk for the TT genotype carriers in rs6749447 decreased after adjustment (OR 0.49, 95% CI 0.19–0.95, P < 0.05). Subjects with haplotype AGACAGGAATCGT showed 1.57 times higher risk of hypertension (95% CI 1.02–2.41, P < 0.05). In conclusion, SNP rs1468326 of WNK1, rs6749447 of STK39, and WNK1 haplotype AGACAGGAATCGT were associated with hypertension in Tibetan individuals. Environ. Mol. Mutagen. 59:151–160, 2018. © 2017 Wiley Periodicals, Inc.
Cholesterol Screening and Statin Prescription is Low Among HIV-Infected Patients on Protease-Inhibitor Regimens in Botswana

Background: Little is known about the use of statin for cardiovascular disease (CVD) risk reduction among HIV-infected patients on protease inhibitors (PI`s) in sub-Saharan Africa (SSA). Objective: Cholesterol screening and statin use were retrospectively assessed among HIV-infected participants on PI`s between 2008 and 2012 at a large urban HIV clinic in Botswana. Methods: Proportion of participants screened per year was calculated and statin indication was assessed using atherosclerosis CVD (ASCVD) and Framingham risk (FRS) scores as of the year 2012 guidelines. Results: Cholesterol screening ranged between 19% and 30% per year (2008-2011) but increased to 80% after study enrollment. The rate of hypercholesterolemia (> 5.0 mmol/L) was 31% in 2012. Fewer than 1% participants were on statin therapy but 14.3% and 9.4% had statins indicated by ASCVD and FRS respectively. Conclusion: The high proportion of participants indicated for, but not prescribed statins highlights a substantial gap in the care to reduce CVD risk among these patients.
Stent patency using competing risk model in unresectable pancreatic cancers inserted with biliary self‐expandable metallic stent

Biliary self‐expandable metallic stents (SEMS) play an important role in the quality of life and palliative treatment in unresectable pancreatic cancer patients. We aimed to determine the factors affecting the patency of biliary SEMS and the survival in unresectable pancreatic cancer with obstructive jaundice.
In Vitro and In Vivo Comparison of the Activity of Human Lymphokine-Activated Killer (LAK) Cells and Adherent LAK Cells

Summary: The effectiveness of “standard” lymphokine-activated killer (LAK) cells, recovered after 6 days, and of “standard” adherent LAK (ALAK) cells, recovered after 14 days of culture in the presence of recombinant interleukin-2 (rIL-2) from peripheral blood lymphocytes of 21 healthy donors, was assessed through comparison of their proliferation, surface markers, cytotoxic activity, lymphokine production, and antitumor activity. In the presence of rIL-2, plastic adherent precursors of A-LAK cells proliferated much better than those of “standard LAK” cells and expanded even more than 300-fold. However, the final cell recovery of A-LAK was always lower because of their very few precursors, and the total lytic units (LUs) generated in A-LAK cultures were always lower for the same reason. On the other hand, the lytic activity of each A-LAK cell was always higher than that of a LAK cell. This was particularly evident on day 6 of culture. Removal of nonadherent cells after the first 24 h culture resulted in a significant enrichment in CD3¯CD56+ and CD8 + CD56+ cells in A-LAK cells, with a marginal number of CD4+ cells. A significant direct correlation between LUs and A-LAK CD3¯CD56+ percentage was found. In the presence of rIL-2, A-LAK cells produced higher amounts of tumor necrosis factor-α and interferon-γ than LAK cells, while only A-LAK cells produced IL-iβ and small amounts of IL-4. Neither LAK nor A-LAK produced IL-2. In the absence of injections of IL-2, LAK and A-LAK cells were equally able to inhibit the growth of a human T-cell lymphoma in immunosuppressed nude mice.
Do axons grow during adulthood? A study of caliber and microtubules of sural nerve axons in young, mature, and aging rats

Calibers and microtubules of sural nerve axons were studied in young (6‐week‐old), mature (14‐week‐old), and aging (2‐year‐old) rats. The mean cross‐sectional area of nonmedullated fibers was about 0.50 μm2 (range: 0.47–0.52) in the three age groups. Their caliber spectra were also similar. In contrast, myelinated axons grew from 6.6 to 16.7 μm2 between the sixth and 14th week of age. The increase of cross‐sectional area was greater, the greater the initial caliber of axon (range 44–154%). No further change of caliber was observed in the aging rat. The cross‐sectional area of nerve allotted per myelinated fiber was 42, 66, and 97 μm2 in young, mature, and aging rats, respectively. The fraction of nerve tissue occupied by the axoplasm, though, did not change substantially; it was 20, 28, and 21%, respectively. The microtubules density of 3‐μm3 myelinated axons had a general average of 21 microtubules μm2. Differences between groups were not significant. In nonmedullated fibers, the microtubular density decreased as the size of the axon increased. No differences were observed between age groups. We conclude that nonmedullated fibers of the sural nerve stop growing before the sixth week whereas myelinated fibers keep growing until the 14th week of age. The correlation between microtubular content and axonal caliber is a lifelong feature of axons.
Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.
The role of the board in voluntary disclosure

Purpose Since 2012, the Brazilian Stock Exchange has recommended that listed companies inform them if they have conducted voluntary disclosure. The purpose of this study is to describe the voluntary disclosure by companies listed in the B3 in Brazil and to analyze which characteristics of the board of directors influence this disclosure. Design/methodology/approach The study involves quantitative research using a sample of 285 companies and 575 reports from 2011 to 2014. A fixed-effects regression model with panel data was used for the analysis. Findings The results were statistically significant for gender and duality variables, which confirms the theory that the presence of women as members of the board positively influences voluntary disclosure and that chief executive officer and chairman of the board positions have a negative effect. The age and independence of the board variables did not present statistical significance. Research limitations/implications As a theoretical contribution, the authors aim to complement sustainability, finance and strategy research by using agency theory and measuring the variable of voluntary disclosure and the board, which is rarely studied in this context. Practical implications As social and empirical contributions, a better understanding of this theme in the context of emerging countries, which is the peculiarities of Brazil with little information transparency and well-known corruption scandals, is likely to aid investors. Increased access to company information can help investors better select their investment portfolios and assist in the choice of their board representatives in companies in which they have participation and voting rights. Originality/value The fact that Brazil is an emerging country, where the lack of transparency of information and corruption in these environments stand out the importance of studying the subject of voluntary disclosure in this context. All data were collected manually specifically for this research.
Inhaled steroids compared with disodium cromoglycate in preschool children with episodic viral wheeze

In school children with atopic asthma the beneficial effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDP) are well‐established. In preschool children, wheezing is quite common, and in the majority of cases the symptoms are episodic and reported to be associated with viral infections rather than atopy. We compared the efficacy of regular treatment with DSCG and BDP for prevention of wheezing in preschool children. We were interested to establish whether regular treatment with inhaled anti‐inflammatory drugs could lead to a decrease in bronchial responsiveness. In 15 patients (median age, 56 months; range, 43–66 months) bronchial responsiveness was assessed by measuring specific airway resistance (sRaw) during a histamine provocation test. The concentration of histamine eliciting a 100% increase in sRaw (PC100his) was determined. In a double‐blind crossover study, patients inhaled either DSCG 10 mg three times a day or BDP 100 μg three times a day for 2 months. After a wash‐out period, treatment was changed to BDP or DSCG, respectively. Daily peak flow measurements were carried out, and exacerbations were noted. PC100his was measured at the start and end of each treatment period.
The Value of the Internal Capital Markets of Business Groups: Evidence from a Structural Estimation

I estimate a dynamic investment model for business groups in which the pyramidal ownership structure generates an agency problem between controlling and minority shareholders. In the model, the controlling shareholder can transfer resources across group firms using intra-group loans, allowing risk sharing and reducing the need for external financing. In a sample of Chilean business groups, I perform counterfactual experiments in which I compare group-affiliated firms with equivalent non-group firms. I find that for the average business group the incremental value of the internal capital market represents roughly 1.5-1.7% of the firm equity value. Although the controlling shareholder gets a larger portion of the value gains, minority shareholders also benefit from these internal transactions.
ARE THE EFFECTS OF UNCONVENTIONAL MONETARY POLICY ON FINANCIAL MARKETS CAUSING BUBBLES?

Cheap money can become very expensive in the long run. Unconventional monetary policies have been the main tools of central banks to tackle the economic crisis. In this paper we aim to understand whether these policies have created distortions in the fi nancial markets and if we can be concerned about the creation of “bubbles”, considering whether quantitative easing has impacted fi nancial asset classes’ valuations beyond reasonable fundamentals. I conclude that there is empirical evidence of inordinate expansion of multiples and that central bank policy makers should include “fi nancial market infl ation” as well as consumer price indices (CPI) in their assessment of infl ation expectations. I believe that this should be an essential analysis to avoid unintended consequences in the future, and a possible next fi nancial crisis that central banks will be unable to face with the same tools of the past.
The Impact of Private and Public Health Insurance on Medication Use for Adults with Chronic Diseases

This article examines the impact of public and private health insurance on the use of medications for California adults with any of four chronic diseases: heart disease, high blood pressure, diabetes, and asthma. The data set used is the 2001 California Health Interview Survey. Multivariate analyses were conducted on individuals who had been diagnosed with each of these diseases. Controlling for various demographic, health status, and employment characteristics, the authors find that the uninsured are far less likely to be taking medications for each of the conditions than those with private insurance. Interestingly, those with Medicaid coverage are even more likely than those with private insurance to be taking such medications. The results of this study underscore the importance of health insurance for all persons with chronic conditions and the benefits of Medicaid in particular for low-income adults with chronic conditions.
Cardiovascular Responses to Apnea during Dynamic Exercise

Breath holding maneuvers induce hypoxia, hypercapnia, and various cardiovascular responses typically including increases in total peripheral resistance, mean arterial pressure (MAP) and decreases in heart rate (HR). During dynamic exercise these responses may have a generally negative impact on performance. Moreover, they deserve particular attention in cardiovascular risk subjects. In 26 healthy sport students we studied the HR and MAP effects induced by the combination of dynamic exercise (cycle ergometry, 30 W and 250 W) with 20 s of either respiratory arrest (mouth piece pressure held constant at 20 mm Hg), free breathing, or rebreathing, i. e. periods of unimpeded breathing leading to similar levels of hypercapnia and hypoxia as the respiratory arrest. The measurements yielded no major differences between the conditions of rebreathing and free breathing. In contrast, 20 s of apnea led to a marked increase in MAP and a HR depression at both levels of exercise intensity. Additionally, there was a delayed MAP recovery after this stimulus. The present findings show that breath holding has marked effects on MAP and HR during dynamic exercise, which are essentially independent of the resulting hypoxia and of increases in intrathoracic pressure. The key factor seems to be an increase in total peripheral resistance, probably including a vasoconstriction in the exercising muscles.