Miracle-dz/UniFAR-FTUs huggingface dataset:
Contrasting Effects of Eplerenone and Spironolactone on Adrenal Cell Steroidogenesis

Spironolactone and eplerenone are widely used as mineralocorticoid antagonists. Spironolactone has several nonspecific actions including inhibition of androgen receptor and steroid hormone biosynthesis. While studies have shown that eplerenone does not exhibit nonspecific actions on androgen receptor, its effects on steroid hormone production have not been reported. Herein, the effects of eplerenone (0.1-30 microM) and spironolactone (0.1-30 microM) on steroid production were examined in human adrenocortical H295R cells. Spironolactone inhibited basal production of cortisol (91%) and aldosterone (53%). Treatment of H295R cells with angiotensin II (Ang II) for 24 h increased aldosterone production by 11-fold. Spironolactone inhibited Ang II stimulation of aldosterone production by 80%. Addition of pregnenolone increased aldosterone (9-fold) and cortisol (3-fold) production. Spironolactone inhibited pregnenolone metabolism to aldosterone (67%) and cortisol (74%). The inhibitory effects of spironolactone occurred at concentrations far higher than those needed to block mineralocorticoid receptor, suggesting an action directly on the enzymes involved in steroid production. In contrast, eplerenone did not inhibit basal, Ang II, forskolin, pregnenolone-stimulated cortisol, or aldosterone production. Together, these data demonstrate that opposed to spironolactone, pharmacologic concentrations of eplerenone do not inhibit adrenal cell aldosterone or cortisol production.
Neuronal systems and circuits involved in the control of food intake and adaptive thermogenesis

With the still‐growing prevalence of obesity worldwide, major efforts are made to understand the various behavioral, environmental, and genetic factors that promote excess fat gain. Obesity results from an imbalance between energy intake and energy expenditure, which emphasizes the importance of deciphering the mechanisms behind energy balance regulation to understand its physiopathology. The control of energy balance is assured by brain systems/circuits capable of generating adequate ingestive and thermogenic responses to maintain the stability of energy reserves, which implies a proper integration of the homeostatic signals that inform about the status of the energy stores. In this article, we overview the organization and functionality of key neuronal circuits or pathways involved in the control of food intake and energy expenditure. We review the role of the corticolimbic (executive and reward) and autonomic systems that integrate their activities to regulate energy balance. We also describe the mechanisms and pathways whereby homeostatic sensing is achieved in response to variations of homeostatic hormones, such as leptin, insulin, and ghrelin, while putting some emphasis on the prominent importance of the mechanistic target of the rapamycin signaling pathway in coordinating the homeostatic sensing process.
Adaptive Neural Network Control for Piezoelectric Hysteresis Compensation in A Positioning System

Piezoelectric (PZT) actuators are popularly applied as actuators in micro-positioning systems due to its characteristic of infinitely small displacement resolution. Piezoelectricity material has nonlinear hysteresis phenomena. Owing to its nonlinear hysteresis effect, the tracking control accuracy of the precision positioning system is difficultly achieved. Hence, it is desirable to take hysteresis effect into consideration for improving the control performance. In this paper, a trajectory tracking controllers composed of adaptive neural network and PI controller is presented for a nano-positioner driven by a piezoactuator to realize the control performance that the displacement of a nano-positioner driven by a piezo-actuator can follow accurately the reference input signal and the transient response of the system can be improved. In this paper, some computer simulations are made to show that the system output can track the reference input exactly and the system transient response can be improved
The “ABC” of Virus‐Specific T Cell Immunity in Solid Organ Transplantation

Transplant patients are at increased risk of viral complications due to impaired control of viral replication, resulting from HLA mismatching between graft and host and the immunosuppression needed to avert alloimmune reactions. In the past decade, quantitative viral load measurements have become widely available to identify patients at risk and to inform treatment decisions with respect to immunosuppressive drugs and antiviral therapies. Because viral loads are viewed as the result of viral replication and virus‐specific immune control, virus‐specific T cell monitoring has been explored to optimize management of adenovirus, BK polyomavirus and cytomegalovirus (“ABC”) in transplant patients. Although most studies are descriptive using different technologies, the overall results show that the quantity and quality of virus‐specific T cells inversely correlate with viral replication, whereby strong cellular immune responses are associated with containment of viral replication. The key obstacles to the introduction of assays for virus‐specific T cells into clinical practice is the definition of reliable cutoffs for clinical decision making, the poor negative predictive value of some assays, and the absence of interventional trials justifying changes of antiviral treatment or immunosuppression. More clinical research is needed using optimized assays and targets before standardization and commutability can be envisaged as achieved for viral load testing.
Altered transmission of HOX and apoptotic SNPs identify a potential common pathway for clubfoot

Clubfoot is a common birth defect that affects 135,000 newborns each year worldwide. It is characterized by equinus deformity of one or both feet and hypoplastic calf muscles. Despite numerous study approaches, the cause(s) remains poorly understood although a multifactorial etiology is generally accepted. We considered the HOXA and HOXD gene clusters and insulin‐like growth factor binding protein 3 (IGFBP3) as candidate genes because of their important roles in limb and muscle morphogenesis. Twenty SNPs from the HOXA and HOXD gene clusters and 12 SNPs in IGFBP3 were genotyped in a sample composed of non‐Hispanic white and Hispanic multiplex and simplex families (discovery samples) and a second sample of non‐Hispanic white simplex trios (validation sample). Four SNPs (rs6668, rs2428431, rs3801776, and rs3779456) in the HOXA cluster demonstrated altered transmission in the discovery sample, but only rs3801776, located in the HOXA basal promoter region, showed altered transmission in both the discovery and validation samples (P = 0.004 and 0.028). Interestingly, HOXA9 is expressed in muscle during development. An SNP in IGFBP3, rs13223993, also showed altered transmission (P = 0.003) in the discovery sample. Gene–gene interactions were identified between variants in HOXA, HOXD, and IGFBP3 and with previously associated SNPs in mitochondrial‐mediated apoptotic genes. The most significant interactions were found between CASP3 SNPS and variants in HOXA, HOXD, and IGFBP3. These results suggest a biologic model for clubfoot in which perturbation of HOX and apoptotic genes together affect muscle and limb development, which may cause the downstream failure of limb rotation into a plantar grade position. © 2009 Wiley‐Liss, Inc.
Challenging trends in configuration research: Where are the configurations?

The configuration approach to the study of organizations is enjoying increasing popularity, in part, due to the methodological advances of qualitative comparative analysis. I argue that there are significant contrasts between earlier taxonomic clustering and typology approaches to configuration and the newer ones being pursued with the qualitative comparative analysis methodology. I compare the two approaches and their application, arguing that what is missing in many studies, old and new, often due to the lack of qualitative evidence, is “configuration itself”—that is, contrasting common, thematic, and rich characterizations that provide insight into how organizations function.
Hormonal regulation of endometrial olfactomedin expression and its suppressive effect on spheroid attachment onto endometrial epithelial cells.

BACKGROUND Olfactomedin (Olfm) is a member of a diverse group of extracellular matrix proteins important for neuronal growth. Recent microarray studies identified Olfm as one of the down-regulated transcripts in receptive endometrium at the time of embryo attachment and implantation. However, the underlying molecular mechanisms that govern Olfm expression and its effect on embryo attachment and implantation remain unknown. METHODS The expression of Olfm in the human endometrium was investigated by real-time PCR, western blotting and immunohistochemistry on human endometrial biopsies from natural and ovarian stimulated cycles. To investigate the function of Olfm in trophoblast-endometrial cell attachment, an in vitro spheroid-endometrial cell co-culture study was performed. RESULTS Human endometrial Olfactomedin-1 and -2(Olfm-1 and -2) transcripts decreased significantly from the proliferative to the secretory phases of the menstrual cycle. Olfm protein was strongly expressed in the luminal and glandular epithelium and moderately in the stromal cells of human endometria. Ovarian stimulation significantly decreased (P < 0.05) the expression of endometrial Olfm-1 and -2 transcripts in patients receiving IVF treatment when compared with those in the natural cycle. Importantly, recombinant Olfm-1 suppressed JAr spheroid attachment onto Ishikawa cells and this was not associated with changes of β-catenin and E-cadherin expression in trophoblast and endometrial cells. CONCLUSIONS Decreased expression of Olfm during the receptive phase of the endometrium may allow successful trophoblast attachment for implantation.
The hepatitis B virus X‐gene product trans‐activates both RNA polymerase II and III promoters.

The transcriptional regulatory activity of the human hepatitis B virus (HBV) X‐gene product was investigated. We demonstrate a new property for the HBV X‐gene, the strong transcriptional trans‐activation of promoters for class III genes. The stimulation of RNA polymerase III (pol III) as well as pol II promoters is shown in cells transiently transfected with the X‐gene, and after its stable integration into hepatocytes. We demonstrate that X‐gene containing cells stimulate the frequency of pol III transcription initiation by 20‐ to 40‐fold, and accelerate the rate of formation of stable pol III initiation complexes in a manner indistinguishable from that of adenovirus E1a protein. Since the transcription factor TFIIIC has been shown to be limiting in the formation of stable pol III initiation complexes, template commitment experiments were performed which titrate the level of this factor in extracts. We show that X‐protein containing extracts are far more efficient in forming stable pol III preinitiation complexes that cannot be competed away upon addition of a second template, indicating that TFIIIC is very probably a target of the X‐protein. Thus, the HBV X‐protein is apparently a member of a family of trans‐activators capable of stimulating both pol II and III promoters, which includes the adenovirus E1a‐protein and SV40 t antigen.
Thin, fast, and flexible

Amorphous silicon has long been the king of flat panel displays. It began its reign in PC monitors and high-definition TV, then conquered netbooks, e-readers, and smartphones. No other substance was as suitable for the thin-film transistors that sit behind a display's hundreds of thousands of pixels, turning each one on or off. But soon the dominion of amorphous silicon will pass, because it can't provide what coming generations of electronic products will require. For one thing, it isn't fast enough. Next-generation LCD TVs will be refreshed at least 240 times a second, which is two to four times as quick as today's versions; that way, they'll provide sharper fast-action sports and movies. Three-dimensional displays will need refresh rates twice again as high, to provide all that fast-motion goodness to each eye.
Theoretical modeling for carrier diffusion coefficient of one-dimensional Si wires around room temperature

This paper uses the semi-microscopic theory to elucidate the effective diffusion coefficient of carriers in one-dimensional Si wire devices. The theoretical model assumes that the primary spectrum of the diffusion process of majority and minority carriers rules the diffusion process; a statistical assessment of the diffusion coefficient is performed based on quantum-mechanical analysis. The theory reveals that the diffusion coefficient drastically decreases as the cross-sectional area falls under the sub-10-nm range.
Characterization of a Strain of Chlamydia pneumoniae Isolated from a Coronary Atheroma by Analysis of theomp1 Gene and Biological Activity in Human Endothelial Cells

ABSTRACT Chlamydia pneumoniae is a respiratory pathogen that has been associated with chronic inflammatory diseases such as asthma and atherosclerosis. Recent isolation of C. pneumoniae from human carotid and coronary atheromas provides additional support for a role of this organism in atherogenesis. We characterized the coronary strain C. pneumoniae A-03 by sequence analysis of the major outer membrane protein gene (omp1). In addition, the in vitro activities of A-03 and three respiratory strains of C. pneumoniae (BAL-16, TW-183, and T-2634) were examined in infected human umbilical vein endothelial cells (HUVEC) by analysis of the production of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and soluble intercellular cell adhesion molecule 1 (sICAM-1). Sequence analysis of omp1 of C. pneumoniaeA-03, compared to prototype strains TW-183 and AR-39, revealed five nucleotide changes resulting in nonsynonymous codons. Of interest was a nonconservative amino acid substitution (Ser to Pro) in position 61 of variable segment 1. In vitro, the extent of MCP-1, IL-8, and sICAM-1 production was dependent on the C. pneumoniae strain examined at low multiplicities of infection following 24 h of incubation. Strain A-03 displayed the lowest stimulatory activity in infected HUVEC, while T-2634 induced the highest levels of MCP-1, IL-8, and sICAM-1 among all strains examined. Heat-inactivated C. pneumoniae failed to stimulate production of these proteins by all strains tested. In contrast, only partial inhibition was observed by UV-inactivated organisms. Results from this study demonstrate that unlike prototype respiratory strains of C. pneumoniae, the coronary strain A-03 displays divergence in the omp1 gene. In addition, the stimulation of chemokines and adhesion molecules involved in the recruitment of leukocytes to sites of inflammation byC. pneumoniae may be important in the pathogenesis of diseases associated with this organism, including atherosclerosis.
Persistence of H5 and H7 Avian Influenza Viruses in Water

Abstract Although fecal–oral transmission of avian influenza viruses (AIV) via contaminated water represents a recognized mechanism for transmission within wild waterfowl populations, little is known about viral persistence in this medium. In order to provide initial data on persistence of H5 and H7 AIVs in water, we evaluated eight wild-type low-pathogenicity H5 and H7 AIVs isolated from species representing the two major influenza reservoirs (Anseriformes and Charadriiformes). In addition, the persistence of two highly pathogenic avian influenza (HPAI) H5N1 viruses from Asia was examined to provide some insight into the potential for these viruses to be transmitted and maintained in the environments of wild bird populations. Viruses were tested at two temperatures (17 C and 28 C) and three salinity levels (0, 15, and 30 parts per thousand sea salt). The wild-type H5 and H7 AIV persistence data to date indicate the following: 1) that H5 and H7 AIVs can persist for extended periods of time in water, with a duration of infectivity comparable to AIVs of other subtypes; 2) that the persistence of H5 and H7 AIVs is inversely proportional to temperature and salinity of water; and 3) that a significant interaction exists between the effects of temperature and salinity on the persistence of AIV, with the effect of salinity more prominent at lower temperatures. Results from the two HPAI H5N1 viruses from Asia indicate that these viruses did not persist as long as the wild-type AIVs.
Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein.

BACKGROUND A possible role of autoimmunity in Alzheimer disease pathogenesis has recently attracted increasing attention. Vaccination with amyloid-beta peptide was reported to cause marked reduction in amyloid deposition, but it also induced encephalitis. Not much is known regarding neurofibrillary tangle-related autoimmune effects. OBJECTIVE To use the main component of tangles-microtubule-associated tau protein-to test the feasibility of active induction of a neuroautoimmune disorder in mice. DESIGN Prospective, randomized controlled animal study. SETTING University medical center research laboratory. Subjects Female C57BL/6 mice. INTERVENTIONS Inoculation with recombinant human tau protein emulsified in complete Freund adjuvant and with pertussis toxin. MAIN OUTCOME MEASURES Clinical, immunologic, pathologic, and behavioral evaluations were performed. RESULTS Vaccination with tau protein induced histopathologic features of Alzheimer disease and tauopathies, indicated by the presence of neurofibrillary tangle-like structures, axonal damage, and gliosis. Also, mononuclear infiltrates without demyelination in the central nervous system, accompanied by neurologic deficits (such as a limp tail and limb paralysis), were observed. Anti-tau antibodies were detected in the serum of tau-immunized mice. CONCLUSIONS These results provide a link between tau autoimmunity and tauopathy-like abnormalities and indicate potential dangers of using tau for immunotherapy. This experimental autoimmune tauopathy-like model is due to a pathogenic immune response against an intraneuronal antigen and is not related to myelin antigens.
Introducing educational interventions for first year medical students in the area of cancer clinical trials: Impact on attitudes and confidence

Background. This study tested the feasibility and efficacy of a multi-faceted educational intervention designed to increase medical students’ confidence in discussing cancer clinical trials with patients. Method. First year students were provided with written resources, problem-based learning scenarios, and an optional practicum. Results. Pre/Post results indicated significant increases in confidence levels; however, these results were tempered with declines in attitudes related to clinical trials. Conclusions. Integrating clinical trials education into existing medical school curriculum is both feasible and desirable. This intervention was successful in increasing students’ confidence levels in discussing clinical trials with patients and deserves continued study.
Early Neurodevelopment in Infants With Deformational Plagiocephaly

AbstractThe objective of this study was to characterize the early neurodevelopmental profile of Australian infants with deformational plagiocephaly (DP). Twenty-one infants with a confirmed diagnosis of DP (mean age, 7.9 months; SD, 2.0 months) were assessed on the Bayley Scales of Infant Development, Second Edition, before treatment. As a group, infants with DP showed significantly weaker motor skills compared with the normative population. Patients with DP did not significantly differ from normative population estimates with respect to cognitive abilities. Males with DP displayed significantly reduced motor abilities compared to females. These findings do not suggest that DP causes developmental problems, but DP could be a marker for risk of developmental problems. Screening for developmental concerns in infants with DP is therefore important.
Speed Sensorless Variable Structure Torque Control of Induction Motor

Induction motor speed sensorless torque control, which allows operation at low and zero speed, optimizing both torque response and efficiency, is proposed. The control is quite different than the conventional field-oriented or direct torque controls. A new discontinuous stator current FPGA based controller and rotor flux observer based on sliding mode and Lyapunov theory are developed, analyzed and experimentally verified. A smooth transition into the field weakening region and the full utilization of the inverter current and voltage capability are possible. The reference tracking performance of speed and rotor flux is demonstrated in terms of transient characteristics by experimental results.
Effects of Inundated Vegetation on X-Band HH–VV Backscatter and Phase Difference

TerraSAR-X HH and HH-VV polarization data of a wetland in Estonia are used to study the effects of HH-VV phase difference on detecting inundated vegetation. Patches with different tree species composition are selected from two images representing flooded and unflooded conditions. Contribution of the double bounce mechanism is studied via phase difference and backscatter analysis. An increase in both HH and HH-VV backscatter was observed for all study cases in flooded conditions, as compared to unflooded periods. Over the different patches, HH backscatter increased from 2.3 dB to 8.2 dB, while for HH-VV - from 3 dB to 9.8 dB. The HH-VV channel allowed for a better separation between flooded and un flooded forest than HH, with the difference between the HH-VV and HH backscatter increase in inundated conditions ranging from 0.2 dB for coniferous stands with a tree height of less than 10 m to 1.6 dB for deciduous stands with a tree height of less than 10 m. A larger separation on both channels was in general observed in deciduous stands as the leaf-off season allowed for a better penetration depth. A considerable phase shift between HH and VV channels ranging from 10° to 28° was observed due to inundation, suggesting a strong contribution from the double bounce mechanism. For unflooded patches, the difference in backscatter between the two acquisition dates ranged from -0.8 dB to 1 dB for HH, and from 0 dB to 2 dB for HH-VV channel. Phase shift for unflooded patches varied from 5° to 8°.
Temporary and Permanent Noise-induced Threshold Shifts: A Review of Basic and Clinical Observations

Objective: To review basic and clinical findings relevant to defining temporary (TTS) and permanent (PTS) threshold shifts and their sequelae. Data Sources: Relevant scientific literature and government definitions were broadly reviewed. Data Synthesis: The definitions and characteristics of TTS and PTS were assessed and recent advances that expand our knowledge of the extent, nature, and consequences of noise-induced hearing loss were reviewed. Conclusion: Exposure to intense sound can produce TTS, acute changes in hearing sensitivity that recover over time, or PTS, a loss that does not recover to preexposure levels. In general, a threshold shift ≥10 dB at 2, 3, and 4 kHz is required for reporting purposes in human studies. The high-frequency regions of the cochlea are most sensitive to noise damage. Resonance of the ear canal also results in a frequency region of high-noise sensitivity at 4 to 6 kHz. A primary noise target is the cochlear hair cell. Although the mechanisms that underlie such hair cell damage remain unclear, there is evidence to support a role for reactive oxygen species, stress pathway signaling, and apoptosis. Another target is the synapse between the hair cell and the primary afferent neurons. Large numbers of these synapses and their neurons can be lost after noise, even though hearing thresholds may return to normal. This affects auditory processing and detection of signals in noise. The consequences of TTS and PTS include significant deficits in communication that can impact performance of military duties or obtaining/retaining civilian employment. Tinnitus and exacerbation of posttraumatic stress disorder are also potential sequelae.