Miracle-dz/UniFAR-FTUs huggingface dataset:
A Mercaptoacetamide-Based Class II Histone Deacetylase Inhibitor Increases Dendritic Spine Density via RasGRF1/ERK Pathway.

BACKGROUND The accumulation of amyloid-β (Aβ) leads to the loss of dendritic spines and synapses, which is hypothesized to cause cognitive impairments in Alzheimer's disease (AD) patients. In our previous study, we demonstrated that a novel mercaptoacetamide-based class II histone deacetylase inhibitor (HDACI), known as W2, decreased Aβ levels and improved learning and memory in mice. However, the underlying mechanism of this effect is unknown. OBJECTIVE Because dendritic spine formation is associated with cognitive performance, here we investigated whether HDACI W2 regulates dendritic spine density and its molecular mechanism of action. METHODS To examine the effect of HDACI W2 on dendritic spine density, we conducted morphological analysis of dendritic spines using GFP transfection and Golgi staining. In addition, to determine the molecular mechanism of W2 effects on spines, we measured the levels of mRNAs and proteins involved in the Ras signaling pathway using quantitative real-time PCR, immunocytochemistry, and western analysis. RESULTS We found that HDACI W2 altered dendritic spine density and morphology in vitro and in vivo. Additionally, W2 increased the mRNA or protein levels of Ras GRF1 and phospho-ERK. Moreover, knockdown of RasGRF1 and inhibition of ERK activity prevented the W2-mediated spinogenesis in primary hippocampal neurons. CONCLUSION Our Class II-selective HDACI W2 promotes the formation and growth of dendritic spines in a RasGRF1 and ERK dependent manner in primary hippocampal neurons.
Mercury(II) binds to both of chymotrypsin's histidines, causing inhibition followed by irreversible denaturation/aggregation

The toxicity of mercury is often attributed to its tight binding to cysteine thiolate anions in vital enzymes. To test our hypothesis that Hg(II) binding to histidine could be a significant factor in mercury's toxic effects, we studied the enzyme chymotrypsin, which lacks free cysteine thiols; we found that chymotrypsin is not only inhibited, but also denatured by Hg(II). We followed the aggregation of denatured enzyme by the increase in visible absorbance due to light scattering. Hg(II)‐induced chymotrypsin precipitation increased dramatically above pH 6.5, and free imidazole inhibited this precipitation, implicating histidine‐Hg(II) binding in the process of chymotrypsin denaturation/aggregation. Diethylpyrocarbonate (DEPC) blocked chymotrypsin's two histidines (his40 and his57) quickly and completely, with an IC50 of 35 ± 6 µM. DEPC at 350 µM reduced the hydrolytic activity of chymotrypsin by 90%, suggesting that low concentrations of DEPC react with his57 at the active site catalytic triad; furthermore, DEPC below 400 µM enhanced the Hg(II)‐induced precipitation of chymotrypsin. We conclude that his57 reacts readily with DEPC, causing enzyme inhibition and enhancement of Hg(II)‐induced aggregation. Above 500 µM, DEPC inhibited Hg(II)‐induced precipitation, and [DEPC] >2.5 mM completely protected chymotrypsin against precipitation. This suggests that his40 reacts less readily with DEPC, and that chymotrypsin denaturation is caused by Hg(II) binding specifically to the his40 residue. Finally, we show that Hg(II)‐histidine binding may trigger hemoglobin aggregation as well. Because of results with these two enzymes, we suggest that metal‐histidine binding may be key to understanding all heavy metal‐induced protein aggregation.
Validity Testing of Technology Acceptance Model Based on Factor Analysis Approach

Successful implementation of Information Technology can be judged or predicted from the user acceptance. Technology acceptance model (TAM) is a model that is built to analyze and understand the factors that influence the acceptance of the use of technologies based on the users perspective. In other words, TAM offers a powerful explanation related to acceptance of the technology and its behavior. TAM model has been applied widely to evaluate various information systems (IS) or information technology (IT), but it is the lack of research related to the evaluation of the TAM model itself. This study aims to determine whether the model used TAM is still relevant today considering rapid development of information communication technology (ICT). In other words, this study would like to test whether the TAM measurement indicators are valid and can represent each dimension of the model. The method used is quantitative method with factor analysis approach. The results showed that all indicators valid and can represent each dimension of TAM, those are perceived usefulness, perceived ease of use and behavioral intention to use. Thus the TAM model is still relevant used to measure the user acceptance of technology.
Fast forward selection for generalized estimating equations with a large number of predictor variables

We propose a new variable selection criterion designed for use with forward selection algorithms; the score information criterion (SIC). The proposed criterion is based on score statistics which incorporate correlated response data. The main advantage of the SIC is that it is much faster to compute than existing model selection criteria when the number of predictor variables added to a model is large, this is because SIC can be computed for all candidate models without actually fitting them. A second advantage is that it incorporates the correlation between variables into its quasi‐likelihood, leading to more desirable properties than competing selection criteria. Consistency and prediction properties are shown for the SIC. We conduct simulation studies to evaluate the selection and prediction performances, and compare these, as well as computational times, with some well‐known variable selection criteria. We apply the SIC on a real data set collected on arthropods by considering variable selection on a large number of interactions terms consisting of species traits and environmental covariates.
Speech Intelligibility Prediction Based on the Envelope Power Spectrum Model with the Dynamic Compressive Gammachirp Auditory Filterbank

In this study, we develop a new method to realize speech intelligibility prediction of synthetic sounds processed by nonlinear speech enhancement algorithms. A speech envelope power spectrum model (sEPSM) was proposed to account for subjective results on a spectral subtraction, but it is untested by recent state-of-the-art speech enhancement algorithms. We introduce a dynamic compressive gammachirp auditory filterbank as the front-end of the sEPSM (dcGC-sEPSM) to improve the predictability. We perform subjective experiments on speech intelligibility (SI) of noise-reduced sounds processed by the spectral subtraction and a recently developed Wiener filter algorithm. We compare the subjective SI scores with the objective SI scores predicted by the proposed dcGC-sEPSM, the original GT-sEPSM, the three-level coherence SII (CSII), and the shorttime objective intelligibility (STOI). The results show that the proposed dcGC-sEPSM performs better than the conventional models.
Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers

Three attenuated Salmonella typhi strains have been constructed by introducing deletions in aroC and aroD or deletions in cya and crp into one of two wild-type parent strains, Ty2 or ISP1820. These mutant strains were designated CVD 906 (ISP1820 delta aroC delta aroD), CVD 908 (Ty2 delta aroC delta aroD), and chi 3927 (Ty2 delta cya delta crp). Two studies were conducted with 36 healthy adult inpatient volunteers to determine in a double-blind fashion the safety and immunogenicity of approximately 5 x 10(4) and 5 x 10(5) CFU of each of these three vaccine candidates given as a single dose. No statistically significant difference in the incidence of reactions among vaccinees was observed. Fever (oral temperature greater than or equal to 38.2 degrees C) occurred in 2 of 12 volunteers who received CVD 906, in 0 of 12 who received CVD 908, and in 1 of 12 who received chi 3927. Vaccine bacteremia without symptoms occurred in 1 of 12 vaccinees who received CVD 906, in 0 of 12 who received CVD 908, and in 2 of 12 who received chi 3927. Overall, 19 (53%) of 36 vaccinees developed immunoglobulin G antibody to S. typhi lipopolysaccharide after vaccination, with no statistically significant differences in the rate of seroconversion among volunteers in the three groups. We conclude that defined mutations in the aromatic biosynthetic pathway and in the cyclic AMP global regulatory system attenuate S. typhi. Mutant strains CVD 906, CVD 908, and chi 3927 are highly (and approximately equally) immunogenic but possibly differ in their propensity to induce fever. Further studies are needed to document the apparent relative safety of CVD 908 as a typhoid vaccine and as a vaccine carrier of foreign antigens.
Human immunodeficiency virus-related lymphomas: a possible association between tumor proliferation, lack of ploidy anomalies, and immune deficiency.

In an attempt to identify a biologic basis for the aggressive clinical behavior of human immunodeficiency virus (HIV)-associated lymphomas (HAL), dual-parameter flow-cytometric analysis was performed on 22 paraffin-embedded biopsy specimens. Cases were analyzed for DNA ploidy, the percentage of cells in S-phase (proliferative activity), and content of a recently identified proliferation-associated nuclear antigen, p105. The DNA-content analysis of 22 HALs was compared with that of 109 cases of intermediate-grade non-Hodgkin's lymphoma (NHL) unrelated to the acquired immune deficiency syndrome (AIDS) studied previously in our laboratory and 125 cases of high-grade NHL reported in the literature. The proliferative activity was higher in intermediate-grade HAL relative to non-AIDS NHL (24.0% v 10.4%; P = .03), and in high-grade HAL in comparison with NHLs of similar histology unassociated with HIV infection (24.8% v 19%), although the latter did not reach statistical significance. The number of mitoses per 10 high-power fields was found to correlate with the percentage of cells in S-phase (r = .68; P = .0004). Although p105 content tended to be higher in HAL than in an AIDS-related complex (ARC)-associated hyperplastic lymph node control, no statistically significant associations were found between p105 content and proliferative activity or the number of mitoses per 10 high-power fields. When compared with non-AIDS NHLs of comparable grade, there was a trend toward a lower incidence of DNA aneuploidy in both intermediate- (25% v 56%) and high-grade (38.5% v 60%) HALs. The higher proliferative activity and lower incidence of DNA aneuploidy found in HAL relative to non-AIDS NHL of comparable histologic grade may represent differences in pathogenesis and may underlie the poor prognosis of HIV-associated NHL.
Echinococcus granulosus in northern Queensland. 1. Prevalence in cattle.

OBJECTIVE To determine the prevalence and geographical distribution of hydatidosis and investigate factors that might be expected to influence the prevalence of hydatids in cattle in Queensland north of the Tropic of Capricorn. To determine the effect of natural levels of infection on carcase weight and subsequent economic loss. PROCEDURE An abattoir survey conducted in 1981 provided information on the distribution, prevalence and viability of hydatid cysts in cattle from all shires north of the Tropic of Capricorn in Queensland. Livers, lungs and spleens from 10,382 cattle were palpated at abattoirs in Cairns, Townsville and Rockhampton to detect hydatid cysts. Prevalence of infection in cattle in each shire was estimated from results of the abattoir study together with reports of infection in a further 22,185 cattle obtained from abattoir records. Linear modelling was used to define the effect of geographical origin, age, breed and sex on prevalence of infection. Differences in the weights of carcases between infected and non-infected cattle of the same age, sex, breed and property of origin were examined. The economic loss to the beef industry in the region surveyed was estimated. RESULTS Cattle infected with hydatids originated almost entirely from regions to the east of the Great Dividing Range. The mean prevalence inside this zone was 28% compared with 3% in other areas. Viable protoscoleces were found in 0.7% of cysts. Geographical origin and age of the cattle were the most significant factors influencing prevalence. Infection with hydatids had no effect on carcase weight. Economic loss was limited to that associated with condemnations of organs at meat inspection, estimated to be 0.5 million dollars per annum in 1981 and 6 million dollars in 2004. The distribution of hydatids in Queensland north of the Tropic of Capricorn corresponded most closely with the distribution of small wallabies such as Macropus dorsalis (black-striped wallaby), M parryi (whiptail wallaby) and M rufogriseus (red-necked wallaby). CONCLUSIONS It was concluded that cattle are not an important part of maintaining the life-cycle of E granulosus in Queensland north of the Tropic of Capricorn. Within the endemic zone, which is almost all to the east of the Great Dividing Range, the local pattern of bovine echinococcosis is most likely to be determined by the presence or absence of small species of wallaby such as M dorsalis, M parryi and M rufogriseus.
Suppression of Ixodes scapularis (Acari: Ixodidae) Following Annual Habitat-Targeted Acaricide Applications Against Fall Populations of Adults

ABSTRACT Spring acaricide applications directed against nymphal Ixodes scapularis have been shown to be effective, but are perceived by the public as having significant adverse environmental impacts, particularly against nontarget organisms. Targeting the adult stage of I. scapularis in the fall would hypothetically result in indirect control of subsequent subadult stages while avoiding other arthropods that are typically inactive during this period. We demonstrate that single fall applications of deltamethrin for 3 consecutive years immediately reduced fall questing adults, while also rapidly reducing the abundance of all postembryonic stages. Deltamethrin applied to the shrub-layer vegetation resulted in levels of control between 97.1% and 100% at 7 days postapplication. Repeated applications against the reproductive stage of I. scapularis progressively reduced the abundance of larvae and nymphs in treated plots, reaching 91.4% and 100% by the conclusion of the study.
Consequences of calcium decline on the embryogenesis and life history of Daphnia magna

ABSTRACT Ambient calcium is declining in thousands of soft-water lake habitats in temperate regions as a consequence of unsustainable forestry practices, decreased atmospheric calcium deposition and acidic deposition. As their exoskeleton is heavily reinforced with calcium, freshwater crustaceans have a high specific calcium requirement relative to other aquatic organisms. Daphnia, in particular, is an ideal crustacean for investigating the consequences of calcium decline because it is an abundant and important member of freshwater zooplankton communities. Although it has been established that adult and juvenile Daphnia have different tolerances to low ambient calcium as a result of their different life stage-specific calcium requirements, the consequences of declining calcium on embryonic development have never been investigated. Here, we describe the distribution of calcium in embryonic stages of D. magna and introduce a novel and easy to use staging scheme. We tested whether calcium can be traced from mothers to their offspring. Finally, we assessed the fitness consequences of maternal provisioning in limiting calcium environments. We found that while embryos require calcium for their development and moulting, they do not equilibrate with environmental calcium levels. Instead, we were able to trace calcium from mothers to their offspring. Furthermore, our data strongly suggest that females are faced with an allocation trade-off between providing calcium to their offspring and using it for growth and moulting. Together, these data provide novel insights into the consequences of calcium decline for freshwater zooplankton. Summary: Ambient calcium is declining in thousands of soft-water lake habitats. Daphnia females provision their offspring with calcium and through that incur a potential allocation trade-off.
Experience-dependent plasticity in the auditory cortex and the inferior colliculus of bats: role of the corticofugal system.

In the big brown bat, Eptesicus fuscus, the response properties of neurons and the cochleotopic (frequency) maps in the auditory cortex (AC) and inferior colliculus can be changed by auditory conditioning, weak focal electric stimulation of the AC, or repetitive delivery of weak, short tone bursts. The corticofugal system plays an important role in information processing and plasticity in the auditory system. Our present findings are as follows. In the AC, best frequency (BF) shifts, i.e., reorganization of a frequency map, slowly develop and reach a plateau approximately 180 min after conditioning with tone bursts and electric-leg stimulation. The plateau lasts more than 26 h. In the inferior colliculus, on the other hand, BF shifts rapidly develop and become the largest at the end of a 30-min-long conditioning session. The shifted BFs return (i. e., recover) to normal in approximately 180 min. The collicular BF shifts are not a consequence of the cortical BF shifts. Instead, they lead the cortical BF shifts. The collicular BF shifts evoked by conditioning are very similar to the collicular and cortical BF shifts evoked by cortical electrical stimulation. Therefore, our working hypothesis is that, during conditioning, the corticofugal system evokes subcortical BF shifts, which in turn boost cortical BF shifts. The cortical BF shifts otherwise would be very small. However, whether the cortical BF shifts are consequently boosted depends on nonauditory systems, including nonauditory sensory cortices, amygdala, basal forebrain, etc., which determine the behavioral relevance of acoustic stimuli.
Dispersion Flattened Porous-Core Honeycomb Lattice Terahertz Fiber for Ultra Low Loss Transmission

We propose the design of a novel porous-core honeycomb lattice photonic crystal fiber (PH-PCF) with extremely low loss and flattened dispersion for guiding terahertz (THz) wave. Finite element method is used to investigate in detail the properties of the designed waveguide. The single modeness, effective material loss (EML), confinement loss (<inline-formula> <tex-math notation="LaTeX">$L_{c}$ </tex-math></inline-formula>), effective modal area, bending loss, distribution of power in different regions, and the dispersion profile of the designed structure are systematically analyzed. Simulation results of the proposed PH-PCF confirm that the bulk material absorption loss of the host material Topas can be reduced by 88.87% using the proposed design. The obtained EML is as low as 0.02227 cm<sup>−1</sup> at operating frequency <inline-formula> <tex-math notation="LaTeX">$f = 1$ </tex-math></inline-formula> THz and the dispersion is ±0.15 ps/THz/cm, flattened over a band of frequency as wide as 1.15 THz. Besides, the reported design also offers negligible <inline-formula> <tex-math notation="LaTeX">$L_{c}$ </tex-math></inline-formula> and relatively smaller bending loss as compared with other contemporary studies.
Buprenorphine effects in methadone-maintained volunteers: effects at two hours after methadone.

Buprenorphine is an opioid partial agonist being developed for possible use in the treatment of opioid dependence. In a previous study up to 8 mg of buprenorphine administered 20 hr after a daily dose of methadone in methadone-maintained volunteers produced neither agonist-like nor antagonist-like effects. The purpose of this study was to examine the effects of buprenorphine challenges given 2 hr after a daily methadone dose in maintained volunteers. Seven male volunteers maintained on 30 mg of methadone daily underwent pharmacologic challenges two to three times per week. Medication challenges consisted of double-blind i.m. injections of buprenorphine (0.5-8.0 mg), the opioid antagonist naloxone (0.1 and 0.2 mg), the prototypic opioid mu agonist hydromorphone (5 and 10 mg) or saline. Assessments of physiologic measures, volunteers' self-reports and observer ratings of drug effects were collected in a laboratory session for 2 hr after drug administration, and then for 8 additional hr postsession. Results from the laboratory session showed that on subject and observer ratings naloxone produced typical antagonist-like effects, hydromorphone produced mild agonist-like effects and buprenorphine produced antagonist-like effects. Interestingly, buprenorphine's antagonist activity was not directly dose-related; its most prominent antagonist effects occurred at the 1- and 2-mg doses. These results are consistent with buprenorphine's action as a partial mu opioid agonist and demonstrate that antagonist-like effects can occur under some conditions suggesting buprenorphine should have a low abuse liability in methadone-maintained patients.
The Allergen-Induced Airway Hyperresponsiveness in a Human-Mouse Chimera Model of Asthma Is T Cell and IL-4 and IL-5 Dependent

The cellular and molecular mechanisms involved in the airway hyperresponsiveness (AHR) of patients with allergic asthma remain unclear. A role for Th2 inflammatory cells was suggested based on murine asthma models. No direct evidence exists on the role of these cells in human asthma. The development of a mouse-human chimera might be useful, allowing the in vivo study of the components of the human immune system relevant to asthma. We investigated the role of allergen-reactive T lymphocytes in a human-mouse SCID model. SCID mice were reconstituted intratracheally with human PBMC from healthy, nonallergic, nonasthmatic donors and exposed to an aerosol of house dust mite allergen after i.p. injection with Dermatophagoides pteronyssinus I Ag and alum. The donor T lymphocytes had a Th1 cytokine phenotype. The reconstituted and allergen-challenged mice developed AHR to carbachol. The mouse airways and lungs were infiltrated with human T lymphocytes. No eosinophils or increases in human IgE were observed. The intrapulmonary human T lymphocytes demonstrated an increase in intracytoplasmic IL-4 and IL-5 and a decrease in IFN-γ after exposure to allergen adjuvant. Antagonizing human IL-4/IL-13 or IL-5 resulted in a normalization of the airway responsiveness, despite a sustained intracellular Th2 cytokine production. These results provide evidence that the activated human allergen-reactive Th2 cells producing IL-4 or IL-5 are pivotal in the induction of AHR, whereas no critical role for eosinophils or IgE could be demonstrated. They also demonstrate that human allergen-specific Th1 lymphocytes can be driven to a Th2 phenotype.