Miracle-dz/UniFAR-FTUs huggingface dataset:
Cholinergic Stimulation of Early Growth Response‐1 DNA Binding Activity Requires Protein Kinase C and Mitogen‐Activated Protein KInase Kinase Activation and Is Inhibited by Sodium Valporate in SH‐SY5y Cells

Abstract : Activation of muscarinic receptors in human neuroblastoma SH‐SY5Y cells with carbachol stimulated a rapid and large increase in early growth response‐1 (Egr‐1, also called zif268 and NGF1‐A) protein levels and DNA binding activity. Egr‐1 DNA binding activity was stimulated within 15 min of treatment with carbachol and maintained a maximum 20‐fold increase over basal between 1 and 2 h after treatment, and the EC50 was ~ μM carbachol. Carbachol‐stimulated Egr‐1 DNA binding activity was dependent on protein kinase C, as it was potently inhibited by GF109203× (IC50 ~0.1 mM) and was reduced by 85 ± 5% by down‐regulation of protein kinase C. Inhibitors of increases in intracellular calcium levels reduced carbachol‐induced Egr‐1 DNA binding activity by 25‐35%. Carbachol‐stimulated activation of Egr‐1 was reduced 35% by genistein, a tyrosine kinase inhibitor, and 60% by PD098059, an inhibitor of mitogen‐activated protein kinase kinases 1/2 (MEK1/2) that activates extracellular‐regulated kinases 1/2 (ERK1/2). A novel inhibitory action was caused by chronic (7‐day) administration of sodium valproate but not by two other bipolar disorder therapeutic agents, lithium and carbamazepine. Valproate treatment reduced carbachol‐stimulated Egr‐1 DNA binding activity by 60% but did not alter carbachol‐induced activation of ERK1/2 or p38 or increases in Egr‐1 protein levels. These results reveal that muscarinic receptors activate Egr‐1 through a signaling cascade primarily encompassing protein kinase C, MEK1/2, and ERK1/2 and that valproate substantially inhibits Egr‐1 DNA binding activity stimulated by carbachol or protein kinase C.
Induction of Broadly Reactive Anti-Hemagglutinin Stalk Antibodies by an H5N1 Vaccine in Humans

ABSTRACT Influenza virus infections are a major public health concern and cause significant morbidity and mortality worldwide. Current vaccines are effective but strain specific due to their focus on the immunodominant globular head domain of the hemagglutinin (HA). It has been hypothesized that sequential exposure of humans to hemagglutinins with divergent globular head domains but conserved stalk domains could refocus the immune response to broadly neutralizing epitopes in the stalk. Humans have preexisting immunity against H1 (group 1 hemagglutinin), and vaccination with H5 HA (also group 1)—which has a divergent globular head domain but a similar stalk domain—represents one such sequential-exposure scenario. To test this hypothesis, we used novel reagents based on chimeric hemagglutinins to screen sera from an H5N1 clinical trial for induction of stalk-specific antibodies by quantitative enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Importantly, we also investigated the biological activity of these antibodies in a passive transfer in a mouse challenge model. We found that the H5N1 vaccine induced high titers of stalk-reactive antibodies which were biologically active and protective in the passive-transfer experiment. The induced response showed exceptional breadth toward divergent group 1 hemagglutinins but did not extend to group 2 hemagglutinins. These data provide evidence for the hypothesis that sequential exposure to hemagglutinins with divergent globular head domains but conserved stalk domains can refocus the immune response toward the conserved stalk domain. Furthermore, the results support the concept of a chimeric hemagglutinin universal influenza virus vaccine strategy that is based on the same principle. IMPORTANCE Influenza virus vaccines have to be reformulated and readministered on an annual basis. The development of a universal influenza virus vaccine could abolish the need for this cumbersome and costly process and would also enhance our pandemic preparedness. This study addressed the following questions, which are essential for the development of a hemagglutinin stalk-based universal influenza virus vaccine. (i) Can stalk-reactive antibodies be boosted by vaccination with divergent HAs that share conserved epitopes? (ii) How long-lived are these vaccine-induced stalk-reactive antibody responses? (iii) What is the breadth of this reactivity? (iv) Are these antibodies functional and protective? Our results further strengthen the concept of induction of stalk-reactive antibodies by sequential exposure to hemagglutinin immunogens with conserved stalk and divergent head domains. A universal influenza virus vaccine based on the same principles seems possible and might have a significant impact on global human health.
Morphologic and Functional Heterogeneity Among Rat Alveolar Macrophage Fractions Isolated by Centrifugation on Density Gradients

Lavaged rat bronchoalveolar cells were separated into four different density fractions (I—IV) by centrifugation through a discontinuous Percoll gradient. Maximum cell size was found in the lowest density fraction (I) and minimal cell size in the highest density fraction (IV), showing an inverse correlation with cell density. These fractions contained alveolar macrophages (AM) in the proportion of 97% or more by morphologic criteria, while phagocytic AM was approximately 80% in each fraction. Although the proportion of la antigen‐positive AM was low in each fraction, it was elevated after incubation with supernatants from concanavalin A (Con A) stimulated spleen cell cultures, with greater la expression in higher density fractions. Differences in these fractions were also noted in several functions, including Fc receptor activity, chemotactic migration, tumoricidal activity, and interleukin 1 (IL‐1) production, all of which were greater in higher density fractions (III and IV). Con A‐induced T cell proliferation was, however, suppressed by these higher density fractions, whereas only an intermediate density fraction (II) enhanced T cell responses. These results indicate morphologic and functional heterogeneity among rat AM.
Do stakeholder management strategy and salience influence corporate social responsibility in Indian companies

Purpose - This study aims to examine whether strategy towards primary stakeholders and their salience influence corporate social responsibility towards the corresponding stakeholders. Design/methodology/approach - Data were collected through a questionnaire from 150 senior level managers including CEOs. The stakeholder management strategy, salience, and corporate social responsibility were assessed in the context of employees, customers, investors, community, natural environment, and suppliers. Findings - The favorable strategy towards stakeholders increases the corresponding corporate social responsibility towards them. The salience of all stakeholder groups also enhances the corresponding corporate social responsibility. When salience and strategy are considered, the salience of a particular stakeholder group suppresses the effect of strategy fully or partially on corporate social responsibility. Research limitations/implications - The salience of a stakeholder is a potent antecedent of corporate social responsibility compared with strategy towards that stakeholder. Originality/value - A questionnaire is developed to assess corporate social responsibility in the Indian context, and the link between strategy, salience, and corporate social responsibility is established.
Antibacterial activity of the essential oils of myrtle leaves against Erysipelothrix rhusiopathiae.

OBJECTIVE To evaluate the antibacterial activity of the essential oil of Myrtus communis (M. communis) L. against Erysipelothrix rhusiopathiae (E. rhusiopathiae) in vitro. METHODS Wild populations of M. communis collected from Khuzestan and Lorestan provinces, Southwest Iran, were examined for antibacterial activity and chemical variability in leaves. The in vitro antibacterial activity against E. rhusiopathiae was performed by agar disc diffusion and micro-dilution assays. RESULTS The essential oils of M. communis have strong antibacterial against E. rhusiopathiae in both assays. The results showed that the major components of the oil were α-pinene (22.3%-55.2%), 1,8-cineole (8.7%-43.8%) and linalool (6.4%-14.5%). The inhibition zones and MIC values for bacteria which were sensitive to the essential oils of M. communis were in the range of 14.7-27.0 mm and 0.031-0.25 mg/mL, respectively. CONCLUSIONS This study demonstrates that products with valuable antibacterial activity can be produced from leaves of M. communis against E. rhusiopathiae.
Preliminary Evaluation of a Semisolid Agar Antifungal Susceptibility Test for Yeasts and Molds

ABSTRACT This report presents a semisolid agar antifungal susceptibility (SAAS) method for the rapid susceptibility screening of yeasts and molds. The reproducibility and accuracy of the SAAS method were assessed by comparing the MICs of amphotericin B and fluconazole obtained for 10 candidate quality control (QC) American Type Culture Collection yeast strains in ≥15 replicates with those found by six independent laboratories using the National Committee for Clinical Laboratory Standards (NCCLS) M27-P broth macrodilution method (M. A. Pfaller et al., J. Clin. Microbiol. 33:1104–1107, 1995). Overall, 96% of MICs for both drugs fell within 1 log2dilution of the modal MIC for each strain. The MICs for amphotericin B showed 99% agreement with the NCCLS proposed QC ranges within 1 log2 dilution. Likewise, the MICs for fluconazole at ≥75% growth reduction showed 99% agreement for seven strains. Three strains, Candida albicans ATCC 24333 and ATCC 76615 and Candida tropicalis ATCC 750, showed a less sharp fluconazole endpoint at ≥75% growth reduction, but at >50% growth reduction, the agreement was 98% within 1 log2 dilution of the proposed range. The MIC agreement within the proposed range for the suggested QC strains Candida parapsilosisATCC 22019 and Candida krusei ATCC 6258 was 100% for fluconazole and 100% within 1 log2 dilution of the proposed range for amphotericin B. The SAAS method demonstrated the susceptibility or resistance of 25 clinical isolates of filamentous fungi such as Aspergillus fumigatus to amphotericin B, itraconazole, and fluconazole, usually within 48 h. Although the results are preliminary, this SAAS method is promising as a rapid and cost-effective screen and is worthy of concerted investigation.
Development of a methodology for the application of synthetic DNA in stream tracer injection experiments

Stream tracer injection experiments are useful for characterizing hydrological and biogeochemical processes in streams. We used nonconservative synthetic DNA and conservative NaCl in six instantaneous tracer injection experiments in streams in the Benelux. The main aim was to compare the performance of injected synthetic DNA tracer “T23” with NaCl. In all experiments, the shapes of the T23 and NaCl breakthrough curves (BTCs) were similar. Recovered T23 mass ranged from 2.9 to 52.6%, while recovered NaCl tracer mass ranged from 66.7% to complete mass recovery. In batch experiments, T23 decay was not detected. However, in those batches, we observed an unexplained initial T23 mass loss of 40–97%. In batches with sediment, T23 attachment rate coefficients ranged from close to zero to 0.2 hr−1. Advective and dispersive transport parameters of both NaCl and T23 fitted with STAMMT‐L were similar. However, compared to T23, fitted storage zone areas of NaCl were 2–5 times larger, while storage zone exchange coefficients were two times larger. Fitted mass dilution factors of T23 ranged from 1.6 to 34.8. Together, these results pointed toward the disappearance of a part of the T23 mass due to both initial losses and attachment or sorption of T23 mass in those storage zone(s), while decay was not important. Our research demonstrated that artificial DNA can be a valuable tool to determine advective and dispersive transport in brooks, but not to assess solute mass exchange processes related to surface transient storage or hyporheic exchange.
The effects of running fewer subjects on time-on-task measures

There is a desire to streamline the development design process by conducting usability evaluations with fewer subjects. This study examined the impact of using fewer subjects on the accuracy and stability of the mean and median. Monte Carlo simulations were conducted to model the skewed task‐completion times typically found in usability studies. The results showed that the mean was a more accurate estimate of its respective population parameter than the median and should be the preferred metric in usability evaluations. However, the mean cannot always be used because it will underestimate the population mean when there are missing data as a result of subjects exceeding time limits. Alternatively, it was found that the median tended to consistently overestimate the population median by as much as 10% in one examined case. The average 95% confidence limits of both estimates were quite broad, particularly for the smaller sample sizes. Based on these results, it was concluded that with reduced sample sizes (e.
The formation of high-redshift submillimetre galaxies

We describe a model for the formation of z ∼ 2 Submillimeter Galaxies (SMGs) which simultaneously accounts for both average and bright SMGs while providing a reasonable match to their mean observed spectral energy distributions (SEDs). By coupling hydrodynamic simulations of galaxy mergers with the high resolution 3D polychromatic radiative transfer code SUNRISE, we find that a mass sequence of merger models which use observ ational constraints as physical input naturally yield objec ts which exhibit black hole, bulge, and H2 gas masses similar to those observed in SMGs. The dominant drivers behind the 850 µm flux are the masses of the merging galaxies and the stellar bir thcloud covering fraction. The most luminous (S850&15 mJy) sources are recovered by ∼10 13 M⊙ 1:1 major mergers with a birthcloud covering fraction close to unity, whereas more average SMGs (S850∼5‐7 mJy) may be formed in lower mass halos (∼5×10 12 M⊙ ). These models demonstrate the need for high spatial resolution hydrodynamic and radiative transfer simulations in matching both the most luminous sources as well as the full SEDs of SMGs. While these models suggest a natural formation mechanism for SMGs, they do not attempt to match cosmological statistics of galaxy populations; future efforts along this line will hel p ascertain the robustness of these models.
A Theory for El Ni�o and the Southern Oscillation

A coupled atmosphere-ocean model is presented for El Ni�o and the Southern Oscillation that reproduces its major features, including its recurrence at irregular intervals. The interannual El Ni�o-Southern Oscillation cycle is maintained by deterministic interactions in the tropical Pacific region. Ocean dynamics alter sea-surface temperature, changing the atmospheric heating; the resulting changes in surface wind alter the ocean dynamics. Annually varying mean conditions largely determine the spatial pattern and temporal evolution of El Ni�o events.
Post-transcriptional Regulation of Acetylcholinesterase mRNAs in Nerve Growth Factor-treated PC12 Cells by the RNA-binding Protein HuD*

Expression of acetylcholinesterase (AChE) is greatly enhanced during neuronal differentiation, but the nature of the molecular mechanisms remains to be fully defined. In this study, we observed that nerve growth factor treatment of PC12 cells leads to a progressive increase in the expression of AChE transcripts, reaching ∼3.5-fold by 72 h. Given that the AChE 3′-untranslated region (UTR) contains an AU-rich element, we focused on the potential role of the RNA-binding protein HuD in mediating the increase in AChE mRNA seen in differentiating neurons. Using PC12 cells engineered to stably express HuD or an antisense to HuD, our studies indicate that HuD can regulate the abundance of AChE transcripts in neuronal cells. Furthermore, transfection of a reporter construct containing the AChE 3′-UTR showed that this 3′-UTR can increase expression of the reporter gene product in cells expressing HuD but not in cells expressing the antisense. RNA gel shifts and Northwestern blots revealed an increase in the binding of several protein complexes in differentiated neurons. Immunoprecipitation experiments demonstrated that HuD can bind directly AChE transcripts. These results show the importance of post-transcriptional mechanisms in regulating AChE expression in differentiating neurons and implicate HuD as a keytrans-acting factor in these events.
Delayed cervical epidural hemorrhage associated with silastic dural implant: case report.

OBJECTIVE AND IMPORTANCE This is the first report of delayed cervical epidural hemorrhage caused by an onlay silastic graft placed over the dura after laminectomy. There are several reports of intracranial hemorrhage associated with silastic implants in the literature. CLINICAL PRESENTATION A 49-year-old woman suddenly developed severe neck pain and quadriplegia during sexual intercourse. A C5-C7 laminectomy had been performed 17 years earlier for cervical stenosis. INTERVENTION Magnetic resonance imaging showed an epidural mass compressing the cord at the level of the previous laminectomy. Laminectomy was performed within 5 hours of symptom onset. Postoperatively, the patient regained leg strength. After 2 months of physical therapy, she had minimal residual leg rigidity and returned to work. TECHNIQUE At surgery, the cervical cord was compressed by a solid fibrous scar surrounding a silastic onlay graft and the dura. An epidural hematoma was beneath the silastic implant. The dense scar tissue, hematoma, and silastic implant were removed. CONCLUSION Bleeding associated with silastic sheets starts with movement of this nonadherent implant. The movement disrupts the underlying fine vessels on the surface of an encasing connective tissue membrane. Overgrowth of this membrane can cause mass effect and simulate a tumor, even without associated bleeding, within weeks. Delayed hemorrhage is more common. We recommend removal of these implants electively, especially if a thick membrane surrounding the dura is detected with postcontrast-enhanced magnetic resonance imaging.
Cardiac involvement in juvenile neuronal ceroid lipofuscinosis (Batten disease)

Objective: To explore the onset and progression of cardiac involvement in juvenile neuronal ceroid lipofuscinosis (JNCL). Methods: The study population comprised an unselected group of 29 children and adolescents with genetically verified JNCL. We focused on T-wave abnormalities on an EKG, cardiac hypertrophy, and left ventricular systolic function on echocardiography, and heart rates and heart rate variability (HRV) on 24-hour EKG recordings. The surviving patients were observed for 7½ years. The 24-hour EKG recording was repeated after 3 years. Results: Abnormally deeply inverted T waves were present in one-third of the initial EKG recordings and were reported as early as 14 years of age. We found coherence between the presence of repolarization disturbances of the ventricular myocardium at the initial recordings and risk of death during the observation period. At increasing age, heart rate and HRV, expressed as the vagal index (number of adjacent RR intervals deviating more than 6%), were significantly reduced, suggesting an age-dependent bidirectional effect of JNCL on heart rate: one through decreasing parasympathetic activity on the heart and the other through a direct negative influence on sinus node automaticity. Coherence between bradycardia and arrhythmia and occurrence of sinus arrests and atrial flutter with increasing age indicated an age-dependent decrease in sinus node activity also. In the early 20s, a high frequency of ventricular hypertrophy occurred. Conclusions: Progressive cardiac involvement with repolarization disturbances, ventricular hypertrophy, and sinus node dysfunction occur in JNCL. We recommend that the attention on heart involvement in JNCL and other neuronal ceroid lipofuscinosis subtypes should be intensified.
Effects of Magnifier Training: Evidence from a Camera Built in the Magnifier

Purpose: This study evaluated the effect of an evidence-based magnifier training on viewing behavior in visually impaired children aged 3 to 6½ years. Methods: Effects of a training with a stand magnifier were evaluated by analyzing recordings of 21 visually impaired children, obtained from a miniature camera mounted in the magnifier. In a pre-test, post-test design, 11 of the children trained without magnifier and 10 children trained with magnifier. Three measures were compared from pre- to post-test assessment: 1) observation time in seconds through the magnifier during task performance; 2) the eye that was used during task performance with the magnifier (right eye/left eye as recorded by the camera); and 3) the self-chosen eye-to-chart distance (in cm) in near visual acuity measurement. Results: Three important changes were found by analyzing the eye-camera recordings: (1) There was a significant shift in average observation time (i.e., the duration of looking through the magnifier in a single glance), before and after training. In the pre-test children used less than 10 s for a glance through the magnifier, whereas in the post-test this was 10–30 s. (2) In 5 children there was no preference with respect to the number of glances through the magnifier with right or left eye during pre-test measurement. However, such a task-specific dominance was clearly observed in this subgroup after training (post-test measurement). (3) The eye-to-chart distance, as measured during near-vision testing with LH-single and LH-line test, decreased significantly over the training period (from 9.5 cm to 7.9 cm, pre- to post-test). There were no differences in the outcome measures between the with-magnifier and without-magnifier training groups. We can conclude that (1) the magnifier training had a positive effect on viewing behavior and the development of dominance, and (2) camera observations provide valuable data on children’s viewing behavior.
Driving Forces of Venture Capital Investments in Europe: A Dynamic Panel Data Analysis

Using dynamic panel estimations, this paper identifies driving forces of venture capital activity for Western European countries. Driving forces might be the liquidity of stock markets, human capital endowment, and labour market rigidities. The paper shows that these factors do not affect expansion stage investments used as a broader definition of venture capital, while they positively affect early stage investments used as a narrow definition. Thus, the results suggest not only that liquid stock markets play an important role for the development of venture capital markets but also that they are not the only factor that drives venture capital activity.
Effect of Pressure on the Behavior of Copper-, Iron-, and Nickel-Based Oxygen Carriers for Chemical-Looping Combustion

The combustion process integrated by coal gasification and chemical-looping combustion (CLC) could be used in power plants with a low energy penalty for CO2 capture. This work analyzes the main characteristics related to the CLC process necessary to use the syngas obtained in an integrated gasification combined cycle (IGCC) power plant. The kinetics of reduction with H2 and CO and oxidation with O2 of three high-reactivity oxygen carriers used in the CLC system have been determined in a thermogravimetric analyzer at atmospheric pressure. The iron- and nickel-based oxygen carriers were prepared by freeze-granulation, and the copper-based oxygen carrier was prepared by impregnation. The changing grain size model (CGSM) was used for the kinetic determination, assuming spherical grains for the freeze-granulated particles containing iron and nickel and a platelike geometry for the reacting surface of the copper-based impregnated particles. The dependence of the reaction rates on temperature was low, with the a.