Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping of angiotensin II receptor subtype heterogeneity in rat brain

Angiotensin II (Ang II) exerts a number of central actions on fluid and electrolyte homeostasis, autonomic activity, and neuroendocrine regulation. In order to evaluate likely sites where these actions are mediated, Ang II receptor binding was localized in rat brain by in vitro autoradiography with the aid of the antagonist analogue l25I‐[Sar1, Ile8]Ang II. Two subtypes of Ang II receptor have been identified using recently developed peptide and nonpeptide antagonists. In the periphery, the receptor subtypes differ in distribution, second messenger coupling, and function. Brain Ang II receptor subtypes were therefore differentiated into AT‐1 (type I) and AT‐2 (type II) subtypes by using unlabelled nonpeptide antagonists specific for the two Ang II subtypes.
Multiple steps in the localization of bicoid RNA to the anterior pole of the Drosophila oocyte.

The anterior region of the Drosophila embryonic pattern is determined by a gradient of the bicoid (bcd) protein. The correct formation of this gradient requires the localization of bcd RNA to the anterior pole of the egg. Here we use a wholemount in situ technique to examine the process of bcd RNA localization during oogenesis and embryogenesis. While bcd protein becomes distributed in a gradient that extends throughout the anterior two thirds of the early embryo, bcd RNA remains restricted to a much smaller region at the anterior pole. The difference between these distributions indicates that the shape of the protein gradient must depend to some extent on the posterior movement of the protein after it has been synthesized. Four distinct phases of bcd RNA localization can be distinguished during oogenesis. Between stages 6 and 9 of oogenesis, the RNA accumulates in a ring at the anterior end of the oocyte. During the second phase, in stage 9-10a follicles, the RNA also localizes to the apical regions of the nurse cells, demonstrating that the nurse cells possess an intrinsic polarity. As the nurse cells contract during stages 10b-11, all of the bcd RNA becomes localized to the cortex at the anterior end of the oocyte. During a final phase that must occur between stage 12 of oogenesis and egg deposition, the RNA becomes localized to a spherical region that occupies a slightly dorsal position at the anterior pole. (ABSTRACT TRUNCATED AT 250 WORDS)
Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation

Sepsis, a potentially fatal clinical syndrome, is mediated by an early (e.g., tumor necrosis factor and IL-1) and late [e.g., high mobility group B-1 (HMGB1)] proinflammatory cytokine response to infection. Specifically targeting early mediators has not been effective clinically, in part because peak mediator activity often has passed before therapy can be initiated. Late-acting downstream effectors, such as HMGB1, that mediate sepsis lethality may be more relevant therapeutic targets. Ethyl pyruvate (EP) recently was identified as an experimental therapeutic that significantly protects against lethal hemorrhagic shock. Here, we report that EP attenuates lethal systemic inflammation caused by either endotoxemia or sepsis even if treatment begins after the early tumor necrosis factor response. Treatment with EP initiated 24 h after cecal puncture significantly increased survival (vehicle survival = 30% vs. EP survival = 88%, P < 0.005). EP treatment significantly reduced circulating levels of HMGB1 in animals with established endotoxemia or sepsis. In macrophage cultures, EP specifically inhibited activation of p38 mitogen-activated protein kinase and NF-κB, two signaling pathways that are critical for cytokine release. This report describes a new strategy to pharmacologically inhibit HMGB1 release with a small molecule that is effective at clinically achievable concentrations. EP now warrants further evaluation as an experimental “rescue” therapeutic for sepsis and other potentially fatal systemic inflammatory disorders.
Understanding and modifying beliefs about climate change through educational travel

Abstract Understanding the factors that shape individuals’ beliefs about climate change is key to the development of effective climate change communication and education strategies. In this study, we test a path model of the social psychological antecedents of beliefs about climate change and evaluate the effectiveness of an educational travel program in changing them. Results show that environmental worldview and affective association with nature are two significant predictors of students’ belief in the occurrence of climate change. Gender was found to influence belief in an anthropogenic causation, while political orientation was a significant predictor of conviction that climate change is occurring. Regression analysis was used to test for changes in climate beliefs before and after participation in an educational travel experience, compared to a control group, using a quasi-experimental design. Results indicate participation strengthened climate change beliefs.
Functional role of efferents to the avian retina. I. Analysis of retinal ganglion cell receptive fields

Receptive fields of retinal ganglion cells were analyzed during extracellular microelectrode recordings in the optic tract of the lightly anesthetized pigeon. Four major types of receptive field can be distinguished among the 359 fibers studied. Twenty‐five percent of the receptive fields are relatively simple, responding at on and at off to stationary spots of light in the central region. All of the receptive fields have inhibitory surrounds of varying strength that do not produce a response when illuminated alone, but antagonize responses from the central region. Motion sensitive units comprise 15% of the recorded population; they are similar to the on‐off center type except that responses to stationary stimuli are absent or very weak while responses to moving stimuli are vigorous. Directionally selective units also have the basic features of on‐off, inhibitory surround cells, but respond to moving stimuli well from the preferred direction and not at all from the null direction. Directional cells have a broad range of null directions; in about one‐third of the units the range becomes broader when the stimulus involves both center and surround of the receptive field, thus enhancing directional selectivity. Directionally selective units are common, comprising 38% of the units studied. Cells unresponsive to stimuli moving from anterior in the visual field are much more common than other types, while cells unresponsive to stimuli from posterior in the field are rare. A few units (11 %) respond only at on or at off to stationary stimuli in their receptive field centers; they also have antagonistic but unresponsive receptive field surrounds. The area of the visual field sampled is uniform in regard to the relative numbers of the four major receptive field types.
MATE CHOICE BASED UPON NATURALLY OCCURRING COLOR‐PATTERN VARIATION IN A GUPPY POPULATION

This study tested the effect of differences in the extent of orange pigment in the color pattern of male guppies on the sexual responsiveness of females. Fish used in this study were descendants of a single natural population from the Paria River of Trinidad. Males from this population have unusually large, brilliant orange spots. I used three experimental approaches to test for discrimination by females among males based on the relative area of orange in color patterns: 1) the time to mating when a male was presented to a virgin female; 2) the frequency of sexual responses of females to passing, nondisplaying males; and 3) the proportion of a male's courtship displays that elicited a female sexual response. In all three experiments, females appeared to discriminate against males with less‐than‐average amounts of orange in their color patterns. In at least one experiment, however, the increase in female responsiveness with increasing amounts of orange leveled off and possibly decreased at high levels of orangeness. This suggests that there may be no advantage of increased amounts of orange above a certain level. These results suggest that female choice is a mechanism for the evolution of color patterns in guppies and may have contributed to the distinctive color pattern of the Paria population.
Metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin by human hepatic CYP isoforms: evidence for selectivity towards CYP3A4

1. The metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (BFBFC) to 7-hydroxy-4-trifluoromethylcoumarin (HFC) was studied in human liver microsomes and in cDNA-expressed human liver CYP isoforms. For purposes of comparison, some limited studies were also performed with 7-benzyloxyquinoline (7BQ). 2. Initial interactive docking studies with a homology model of human CYP3A4 indicated that BFBFC was likely to be a selective substrate for CYP3A4 with a relatively high binding affinity, due to the presence of several key hydrogen bonds with active site amino acid residues. 3. Kinetic analysis of NADPH-dependent BFBFC metabolism to HFC in three preparations of pooled human liver microsomes revealed mean (+/- TSEM) Km and Vmax = 4.6 +/- 0.3 microM and 20.0 +/- 3.8 pmol/min/mg protein, respectively. 4. The metabolism of BFBFC to HFC was determined in a characterized bank of 24 individual human liver microsomal preparations employing a BFBFC substrate concentration of lO microM (i.e. around twice Km). Good correlations (r2 = 0.736-0.904) were observed between BFBFC metabolism and markers of CYP3A isoforms. 5. While 10O microM BFBFC was metabolized to HFC by cDNA-expressed CYP3A4, little or no metabolism was observed with cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 6. The metabolism of 10 microM BFBFC in human liver microsomes was markedly inhibited by 5-50 microM troleandomycin and 0.2-5 microM ketoconazole, but stimulated by 0.2-10 microM alpha-naphthoflavone. The metabolism of 10 microM BFBFC in human liver microsomes was also markedly inhibited by an antibody to CYP3A4. 7. Kinetic analysis of NADPH-dependent 7BQ metabolism to 7-hydroxyquinoline (7HQ) in human liver microsomes revealed Km and Vmax = 70 microM and 3.39 nmol/min/mg protein, respectively. 8. While 80 microM 7BQ was metabolized to 7HQ by cDNA-expressed CYP3A4, only low rates of metabolism were observed with cDNA-expressed CYPIA2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 9. In summary, by correlation analysis, the use of cDNA-expressed CYP isoforms, chemical inhibition and inhibitory antibodies, BFBFC metabolism in human liver microsomes appears to be primarily catalysed by CYP3A4. BFBFC may be a useful fluorescent probe substrate for human hepatic CYP3A4, but compared with 7BQ has only a low rate of metabolism in human liver microsomes.
Nitrate- and nitrite-sensing protein NarX of Escherichia coli K-12: mutational analysis of the amino-terminal tail and first transmembrane segment

Nitrate and nitrite control of anaerobic respiratory gene expression is mediated by dual two-component regulatory systems. The sensors NarX and NarQ each communicate nitrate and nitrite availability to the response regulators NarL and NarP. In the presence of nitrate, the NarX protein acts as a positive regulator ("kinase") of both NarL and NarP activity. In the presence of nitrite, the NarX protein acts primarily as a negative regulator ("phosphatase") of NarL activity but remains a positive regulator of NarP activity. In other topologically similar sensory proteins, such as the methyl-accepting chemotaxis proteins, the transmembrane regions are important for signal transduction. We therefore used localized mutagenesis of the amino-terminal coding region to isolate mutations in narX that confer an altered signaling phenotype. Five of the mutations studied alter residues in the amino-terminal cytoplasmic tail, and five alter residues in the first transmembrane segment. Based on patterns of target operon expression in various regulatory mutant strain backgrounds, most of the mutant NarX proteins appear to have alterations in negative control function. One mutant, with a change of residue Leu-11 to Pro in the cytoplasmic tail, exhibits strikingly altered patterns of NarL- and NarP-dependent gene expression. We conclude that the amino terminus of the NarX protein is important for the differential response to nitrate and nitrite.
Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis.

OBJECTIVE To compare the levels of biogenic amines in the cerebrospinal fluid (CSF) of primary fibromyalgia syndrome (PFS) patients with those in the CSF of controls. METHODS Metabolites of serotonin, norepinephrine, and dopamine were identified in CSF, using high performance liquid chromatography with coulometric detection. RESULTS CSF levels of metabolites from all 3 neurotransmitters were lower in PFS patients than in controls. CONCLUSION A low rate of turnover of several neurotransmitters supports the proposed hypothesis of a metabolic defect in PFS and suggests that the defect occurs at a neuroregulatory level.
Land Transfer Strategy and Industrial Structure Upgrading —Analysis Based on Geographical Externality

Based on 251 prefecture-level cities in China from 2003 to 2014, this paper examines the impact of land transfer strategies of local governments on the upgrading of industrial structure from the perspective of the first and second geographical externalities. The study found that: the local government land transfer strategy can improve the pace of local evolution from primary industry to secondary and tertiary industry; by increasing its relative share, it is conducive to upgrading the quantity of industrial structure upgrading; the local government land transfer strategy has uncertainties on the qualitative impact of industrial structure upgrading; the local government land transfer strategy has uncertainties; The influence of land transfer strategy on the rationalization of industrial structure is uncertain. Local government’s land transfer strategy enhances local government’s land transfer funds, strengthens local government’s financial resources, and local government promotes the amount of industrial structure upgrading through the allocation of financial input. In terms of geographical externalities, the land transfer strategy of local governments is competitive, and the land transfer strategy of local governments can easily lead to the competition of funds, technology, talents and other resources among local governments.
Induced Price Leadership and (Counter-)Spying Rivals' Play Under Incomplete Information

We analyze spying out a rival’s price in a Bertrand market game with incomplete information. Spying transforms a simultaneous into a robust sequential moves game. We provide conditions for profitable espionage. The spied at firm may attempt to immunize against spying by delaying its pricing decision if its cost is low. This, however, adversely affects beliefs and becomes self-defeating. The spy may also be a counterspy or be fooled to report strategically distorted information. This gives rise to an intriguing signaling problem that admits only partially separating equilibria. Surprisingly, counter-espionage may aggravate the price leadership induced by spying. Altogether, our analysis offers an explanation and generalization of robust Stackelberg-Bertrand games.
Automated characterization of the fetal heart in ultrasound images using fully convolutional neural networks

Automatic analysis of fetal echocardiography screening images could aid in the identification of congenital heart diseases. The first step towards automatic fetal echocardiography analysis is locating the fetal heart in an image and identifying the viewing (imaging) plane. This is highly challenging since the fetal heart is small with relatively indistinct anatomical structural appearance. This is further compounded by the presence of artefacts in ultrasound images. Herein we provide a state-of-art solution for detecting the fetal heart and classifying each individual frame as belonging to one of the standard viewing planes using fully convolutional neural networks (FCNs). Our FCN model achieves a classification error rate of 23.48% on real-world clinical ultrasound data. We also present comparative performance for analysis of different FCN architectures.
Fluoxetine as a treatment for post-traumatic stress disorder.

OBJECTIVE To assess the effectiveness of fluoxetine in the treatment of post-traumatic stress disorder (PTSD) in adults. METHODS A meta-analysis was conducted between April 2008 and December 2010 at West China Hospital, Chengdu, China. Any randomized controlled trials (RCTs) in which fluoxetine were used for PTSD were considered through computerized databases up to September 2010 such as MEDLINE, EBSCO, EMBASE, and ELSEVIER. The RCTs were strictly assessed by investigators for inclusion in the study, collated trial data, and trial quality. The results of 7 RCTs included were combined in this meta-analysis to determine the effectiveness of fluoxetine on PTSD. RESULTS Significant findings from the randomized and placebo-controlled trials suggest that fluoxetine could be an effective medication for PTSD (Respond: relative risk=1.21, 95% confidence interval [CI]: 1.03-1.43; Davidson Trauma Scale total score: weighted mean differences=-7.73, 95% CI: -11.69-3.76). In addition, fluoxetine can cause fairly mild adverse effects for those PTSD patients. CONCLUSION Findings suggest that fluoxetine is an effective treatment for PTSD, with mild adverse effects on individuals.
Imaging cardiac morphology in hypertrophic cardiomyopathy: recent advances

Purpose of review To describe new cardiac MRI (CMR) findings on cardiac structure and myocardial composition in hypertrophic cardiomyopathy (HCM). Recent findings Quantitative CMR assessment of replacement fibrosis and interstitial fibrosis can risk stratify HCM patients for adverse outcomes. Patients with global LVH (increased LV mass index) have more adverse outcomes. The HCM phenotype with a spiral distribution of hypertrophy entails a good prognosis. Myocardial noncompaction can be associated with HCM, as are papillary muscle and mitral apparatus abnormalities. Genotype positive, phenotype negative relatives of HCM probands may be detected by myocardial motion abnormalities. Emerging CMR methods for myocardial fiber disarray and altered myocardial stiffness may shed more light on cardiac structure, function and outcomes in HCM in coming years. Summary CMR structural features of HCM, including severity and distribution of hypertrophy and fibrosis, can augment clinical evaluation of HCM. New CMR phenotypes, associated papillary muscle, mitral leaflet and myocardial noncompaction abnormalities, role of left atrial enlargement, findings in genotype positive phenotype negative HCM, and emerging methods for the detection of myocardial fiber disarray and altered myocardial stiffness may shed light in coming years.
The long-term effects of compressed gas diving on lung function in New Zealand occupational divers: a retrospective analysis.

OBJECTIVES Long-term effects of occupational diving on lung function are uncertain. No previous study has been conducted on New Zealand occupational divers. The aim of this study was to investigate changes in divers' lung function over a five year period. METHODS The lung function data of all occupational divers with two spirometric determinations separated by a five year interval (N = 336 out of 1,475 currently registered divers) were entered into a database and analysed for changes (5.6 years mean). The trends were correlated against gender, smoking status and years of diving experience (as more accurate diving exposure data were not available). Spirometric indices were compared with predicted reference values derived from New Zealand (WRS), Australian (Gore), and American (NHANES III and Knudson) populations. RESULTS Small, but signifi cant, decreases were found in FEV1 (0.27% against predicted per annum, P = 0.02) and PEF (0.47% per annum, P = 0.04) using the NHANES III equations. No other changes in lung function parameters reached statistical significance (P < 0.05) using any of the four sets of prediction equations. No changes correlated significantly with reported years diving. CONCLUSION Observed changes to occupational divers' lung function tests over 5.6 years were small and unrelated to years of diving, which might be due to a 'healthy worker effect'. Clinical relevance is unlikely, but this requires further evaluation. There was significant disparity in normative values derived from the four sets of prediction equations and there is some consequential concern about the ongoing utility of such surveillance of New Zealand professional divers.
Histologic features of conjunctival melanoma predictive of metastasis and death (an American Ophthalmological thesis).

PURPOSE In conjunctival melanoma, tumor thickness and nonlimbal location are associated with poor prognosis. However, other established high-risk features for cutaneous melanoma, including ulceration, mitotic figures, epithelioid cell type, and lymphovascular invasion, have not previously been studied extensively for their prognostic value in conjunctival melanoma. We examined the hypothesis that these features also predict regional nodal metastasis and death in conjunctival melanoma. METHODS The medical records of 44 of 46 consecutive conjunctival melanoma patients treated between June 2003 and December 2009 were retrospectively reviewed; tumor tissue was not available for the two excluded patients. Demographic and clinicopathologic features, including tumor location, tumor thickness, ulceration, mitotic rate, histology, lymphovascular invasion, and microsatellitosis, were reviewed. Outcome measures included regional nodal metastasis, distant metastasis, and death. RESULTS Twenty-six women and 18 men had a median age of 62 years. Regional nodal metastasis occurred in 7 patients (16%) and distant metastasis in 9 (20%). Median follow-up was 40 months. At last follow-up, 10 patients (23%) had died of disease. Tumor thickness>2.0 mm, ulceration, and mitotic figure>1/mm2 predicted regional nodal metastasis and death from disease. In addition to these three histologic features, vascular invasion, epithelioid cell type, and microsatellitosis significantly predicted death from disease. Tumor location (bulbar vs nonbulbar) was not correlated with regional nodal metastasis or death. CONCLUSIONS In conjunctival melanoma, as in cutaneous melanoma, thicker tumor, ulceration, and higher mitotic rate are correlated with regional nodal metastasis. In addition, lymphovascular invasion, epithelioid cell type, and microsatellitosis are correlated with melanoma-related death.