Miracle-dz/UniFAR-FTUs huggingface dataset:
PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients

ABSTRACT Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this organism. To explore the role of PhoPQ in high-level clinical polymyxin resistance, P. aeruginosa strains with colistin MICs > 512 mg/liter that had been isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin E) were analyzed. Probable loss-of-function phoQ alleles found in these cystic fibrosis strains conferred resistance to polymyxin. Partial and complete suppressor mutations in phoP were identified in some cystic fibrosis strains with resistance-conferring phoQ mutations, suggesting that additional loci can be involved in polymyxin resistance in P. aeruginosa. Disruption of chromosomal phoQ in the presence of an intact phoP allele stimulated 4-amino-l-arabinose addition to lipid A and induced transcription from the promoter of the pmrH (arnB) operon, consistent with the known role of this lipid A modification in polymyxin resistance. These results indicate that phoQ loss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa.
Tax policy, social inequality and growth

The effects of social inequality usually include income inequality. Income inequality is augmented or reduced by tax policies. This paper finds empirical evidence that shifting the tax burden from the socially disadvantaged to the socially advantaged would cause gross domestic product (GDP) to rise. Specifically, this paper uses Reiterative Truncated Projected Least Squares – a regression technique that produces reduced-form estimates while solving the omitted variables’ problem – to estimate dGDP/d(Property Tax), dGDP/d(Corporate Tax), dGDP/d(Individual Tax) and dGDP/d(Sales Tax) for 23 countries using annual data from 1970 to 2012. GDP is measured in millions of US dollars and each tax is tax revenues as a per cent of GDP. For 13 of the 23 countries examined after 2008, we find that property and corporate taxes are the best taxes (increases GDP the most) to increase and individual income taxes and sales taxes are the worse to raise.
Evaluation of Systemic Inflammatory Response Biomarkers in Patients Receiving Chemotherapy for Unresectable and Recurrent Advanced Gastric Cancer

Background: The present study sought to evaluate an inflammation-based prognostic score (Glasgow prognostic score, GPS) and the neutrophil to lymphocyte ratio (NLR) as prognostic factors in patients receiving chemotherapy for advanced gastric cancer. Methods: The study enrolled 224 patients who received chemotherapy for advanced gastric cancer at the Kochi Medical School from 2007 to 2014. Clinicopathological information and systemic inflammatory response data were obtained to investigate associations between baseline cancer-related prognostic variables and survival outcomes. Results: The median survival time was significantly higher for patients with intestinal-type compared to diffuse-type histology (p = 0.039), a GPS 0 score compared to GPS 1 or 2 score (p = 0.004), and lower compared to higher NLR 4 (p = 0.002). Multivariate survival analysis identified high NLR 4 (HR 1.651; 95% CI 1.187-2.297; p = 0.003) and diffuse-type histology (HR 1.645; 95% CI 1.025-2.639; p = 0.039) as significant independent predictors associated with worse prognosis in the studied group of cancer patients. Conclusions: NLR and histological type are independent prognostic factors for patients receiving chemotherapy for unresectable and recurrent gastric cancer.
The rice transcription factor IDEF1 directly binds to iron and other divalent metals for sensing cellular iron status.

Iron is essential for most living organisms and its availability often determines survival and proliferation. The Oryza sativa (rice) transcription factor IDEF1 plays a crucial role in regulating iron deficiency-induced genes involved in iron homeostasis. In the present report, we found characteristic histidine-asparagine repeat and proline-rich regions in IDEF1 and its homolog in Hordeum vulgare (barley), HvIDEF1. An immobilized metal ion affinity chromatography assay revealed that IDEF1 and HvIDEF1 bind to various divalent metals, including Fe(2+) and Ni(2+) . Recombinant IDEF1 protein expressed in Escherichia coli contained mainly Fe and Zn. This metal-binding activity of IDEF1 was almost abolished by deletion of the histidine-asparagine and proline-rich regions, but DNA-binding and trans-activation functions were not impaired by the deletion. Transgenic rice plants constitutively overexpressing IDEF1 without these metal-binding domains failed to cause pleiotropic effects conferred by overexpression of full-length IDEF1, including a low germination rate, impaired seedling growth, tolerance to iron deficiency in hydroponic culture, and enhanced expression of various iron deficiency-inducible genes. Impairment of the transcriptional regulation of IDEF1 by deletion of the metal-binding domains occurred primarily at an early stage of iron deficiency. These results suggest that the histidine-asparagine and proline-rich regions in rice IDEF1 directly bind to divalent metals and sense the cellular metal ion balance caused by changes in iron availability.
MRI vs. histologic measurement of breast cancer following chemotherapy: Comparison with x‐ray mammography and palpation

Twenty consecutive patients with breast cancer were evaluated following chemotherapy using MRI to assess the size of cancer residua and compare these data with subsequent histologic measurements of the viable tumor. This retrospective study also involved assessment of the preoperative size of the malignancy as determined by physical exam and x‐ray mammogram. These values were later compared with the histology. The tumor size correlation coefficient between MRI and pathologic analysis was the highest, at 0.93. Physical exam and x‐ray mammography (available for 17 patients) produced correlation coefficients of 0.72 and 0.63, respectively, compared to histologic measurement. The accuracy of MRI did not vary with the size of cancer residua. MRI is an accurate method for preoperative assessment of breast cancer residua following chemotherapy. J. Magn. Reson. Imaging 2001;13:868–875. © 2001 Wiley‐Liss, Inc.
Time Dependence of Cellular Chemical Changes Induced in Prostate PC-3 Cancer Cells by Two Structurally Related Cardenolides Monitored by Fourier Transform Infrared (FT-IR) Spectroscopy

Human PC-3 prostate cancer cells were incubated in the presence of two cardenolides, i.e., ouabain and 19-hydroxy-2“-oxovoruscharin. Their effects were monitored by infrared spectroscopy of the cells after different exposure times to the cardenolides. Analysis of changes in absorbance intensities indicated that, for both compounds, the absorbance at one wavenumber with a minor contribution of a second wavenumber is sufficient to build a linear model accurate enough to assign more than 97% of the spectra to their correct time slot. Student t-tests and two-dimensional correlation analysis (2D-COS) indicated that both drugs have very similar effects on PC-3 cells. However, asynchronous 2D maps revealed significant differences and allowed the sequence of the spectral changes to be determined: 1395 → 1695 cm−1 for ouabain, and 1400 → 1655 → 1100 → 1250 → 1020 cm−1” for 19-hydroxy-2“-oxovoruscharin. 2D correlation map subtraction allowed the identification of very specific differences in the impact of both compounds on PC-3 cells, in particular the ability of 19-hydroxy-2”-oxovoruscharin to affect nucleic acid of PC-3 cells.
Order Flows, Delta Hedging and Exchange Rate Dynamics

This paper proposes a microstructure model of the FX options and spot markets. On both market segments, dealers receive customer order flows and use this private information strategically to speculate during interdealer rounds. This non-payoff information is first impounded in private dealers’ inventories before affecting prices. Derivative trading impacts the equilibrium exchange rate via feedback effects of delta hedging strategies followed by option dealers to cover the FX risk embedded in their options portfolio. It is shown that depending on the correlation between spot and option order flows, the volatility of the exchange rate can either be amplified or reduced. JEL Classification: F31, D4, D82, D84, G13.
Curcumin reduces burn progression in rats.

OBJECTIVES Cutaneous burns are dynamic injuries with a central zone of necrosis surrounded by a zone of ischemia. Conversion of this ischemic zone to full necrosis over the days following injury is due in part to highly reactive oxygen radicals. Curcumin is a component of the Oriental spice turmeric that has been shown to have antioxidant and antiapoptotic properties. The authors hypothesized that treatment of burns with curcumin would reduce the conversion of the ischemic zone to full necrosis. METHODS This was a randomized controlled experiment. Twenty Sprague-Dawley rats were used. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20-mm full-thickness burns separated by three 5 x 20-mm unburned interspaces (zone of ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30 minutes before injury and at 24, 48, and 72 hours after injury. Wounds were observed at one, two, and three days after injury for visual evidence of necrosis in the unburned interspaces. Full-thickness biopsy specimens from the interspaces were evaluated with hematoxylin and eosin staining seven days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi-square tests. RESULTS Forty comb burns with 120 unburned interspaces were created, evenly distributed between curcumin and vehicle alone. The percentage of interspaces that progressed to full-thickness necrosis at one, two, three, and seven days after injury in the curcumin and vehicle groups were 30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p = 0.02), and 63% versus 95% (p = 0.02), respectively. CONCLUSIONS Pretreatment of rats with oral curcumin followed by once-daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.
Tackling Epistemological Naivety: Large-Scale Information Systems and the Complexities of the Common Good

We have arrived at a situation in which policymakers and ethicists are considering abandoning informed consent in the governance of certain new technologies, many of which are related to large-scale information systems. A paradigm case is the problem with using individuals’ informed consent to regulate biobanks. As sometimes suggested, there is a need for “new ethical frameworks. ”
[Effects of insulin-like growth factor-1 on the myocardium in diabetic rats].

OBJECTIVE To observe the effects of insulin-like growth factor-1(IGF-1) on myocardial fibrosis and myocardial cell apoptosis in diabetic rats, so as to clarify the potential benefit of IGF-1 on diabetic cardiomyopathy. METHODS Diabetic rats were induced by caudal injection of STZ, and the diabetic rats were randomly divided into 3 groups:diabetes group, the insulin treatment group and the IGF-1 treatment group.Normal control (NC) group did not receive any therapy. The experiment lasted 10 weeks and the heart weight was recorded to calculate the heart weight index. The serum insulin and IGF-1 level were determined.HE staining and Masson staining were taken on the left ventricular tissue. The cardiomyocyte apoptosis were measured by methods of terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) , the expression levels of IGF-1R in cardiomyocytes were measured by immunohistochemical and Western blot. RESULTS Compared with diabetes group, the heart weight index of the insulin treatment group and the IGF-1 treatment group were significantly decreased. Serum levels of IGF-1 in diabetes group were significantly decreased compared with NC group, and the levels were significantly increased in IGF-1 treatment group. The results of HE and Masson staining showed that compared with NC group, diabetes rats' myocardial tissue were damaged. Myocardial tissue pathological changes of rats were significantly improved after insulin and IGF-1 treatment. The result of TUNEL indicant cardiomyocyte apoptosis index in diabetes group was obviously increased than the NC group, and that in IGF-1 treatment group were decreased compared with diabetes group. IGF-1R levels in diabetic rats myocardial tissue were rised than the NC group, it was declined in IGF-1 treatment group, but in insulin treatment group the levels had no obvious change. CONCLUSIONS IGF-1 can inhibite the myocardial fibrosis and cardiomyocyte apoptosis. It maybe have the possible effect on the treatment of diabetic cardiomyopathy.
Markets and Operations - Summer Qb 2005

This article reviews developments since the Spring Quarterly Bulletin in sterling financial markets, UK market structure and the Bank's official operations. Short-term nominal sterling interest rates fell as market participants appeared to revise downwards their views on the likely future path of monetary policy. Longer-term sterling forward rates also fell. In effective terms, sterling depreciated. UK equity prices declined over the review period, perhaps reflecting a perception of a slightly weaker outlook for UK companies' earnings prospects, and/or a revision to investors' risk appetite. The Bank of England implemented interim reforms to its operations in the sterling money markets.
Dietary fat preference and effects on performance of piglets at weaning

Objective An experiment was to evaluate the interplay of dietary lipid sources and feeding regime in the transition from sow milk to solid food of abruptly weaned piglets. Methods Soon after weaning, 144 piglets were selected and were trained over a 15 day period to experience gradually reducing dietary fat content from 12% to 6% for lard (L), soybean oil (S), and coconut oil (C) and their feeding behavior and diet preference then tested in a behavior observation experiment. Another 324 weaned piglets were used in three consecutive feeding experiments to measure the effect of different dietary fats on performance and feed choice in the four weeks after abrupt weaning. The lipid sources were used as supplements in a 3% crude fat corn/soya basal diet, with 6% of each being included to form diets 9C, 9S, and 9L respectively, and their effects on performance measured. Combinations of these diets were then further compared in fixed blends or free choice selection experiments. Results Piglets pre-trained to experience reducing lipid inclusion showed different subsequent preferences according to lipid source, with a preference for lard at 9%, soybean oil at 3%, and coconut oil at 6% inclusion rate (p<0.001). Following abrupt weaning, whilst after 4 weeks those fed 9C had the heaviest body weights (18.13 kg, p = 0.006). Piglets fed a fixed 1:1 blend of 9C+9S had a poorer feed conversion ratio (FCR = 1.80) than those fed a blend of 9C+9L (FCR = 1.4). The 9C and 9L combination groups showed better performance in both fixed blend and free choice feeding regimes. Conclusion After abrupt weaning, they still have dependence on high oleic acid lipids as found in sow milk. A feeding regime offering free choice combination of lipids might give the possibility for piglets to cope better with the transition at weaning, but further research is needed.
Molecular Taxonomy of the Genus Chlorobium

This review summarizes molecular studies on the taxonomy of the genusc Chlorobium. Furthermore, we try to introduce a comprehensive view of how joining traditional phenotypic-based taxonomy with the current molecular approaches leads to a more natural classification. Moreover, we introduce the current insights that molecular techniques have brought to the detection and identification of nonisolated Chlorobium strains in their environments
A Noise Reconfigurable All-Digital Phase-Locked Loop Using a Switched Capacitor-Based Frequency-Locked Loop and a Noise Detector

Programmability is one of the most significant advantages of a digital phase-locked loop (PLL) compared with a charge-pump PLL. In this paper, a digital PLL that extends programmability to include noise is introduced. A digitally controlled oscillator (DCO) using a switched capacitor for frequency feedback is proposed to maintain a constant figure of merit while reconfiguring its noise performance. The proposed DCO offers an accurate and linear frequency tuning curve that is insensitive to environmental changes. A noise detection circuit using the statistical property of a bang-bang phase and frequency detector is proposed to autonomously adjust the output noise level depending on the noise specification. A prototype design is fabricated in a 28-nm FDSOI process. The integrated phase noise of the proposed PLL can be configured from 2.5 to 15 ps, while the power consumption ranges from 1.7 to 5 mW.
Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression

As its role in tumor progression emerges, the PI3K/PKB (Akt) pathway presents an appealing cancer therapeutic target. Recent studies have investigated the mechanisms underlying the tumor-promoting effects of this pathway. PKB triggers a network that positively regulates G1/S cell cycle progression through inactivation of GSK3-beta, leading to increased cyclin D1, and inhibition of Forkhead family transcription factors and the tumor suppressor tuberin (TSC2), leading to reduction of p27Kip1. The identification of p21Waf1/Cip1 and p27Kip1 as novel substrates of PKB provided new insights into mechanisms whereby hyperactivation of this lipid signaling pathway may lead to cell cycle deregulation in human cancers. The PI3K pathway may also play a key role in the G2/M transition and its constitutive activation may lead to defects in DNA damage checkpoint control.
Biological weathering and the long‐term carbon cycle: integrating mycorrhizal evolution and function into the current paradigm

The dramatic decline in atmospheric CO2 evidenced by proxy data during the Devonian (416.0–359.2 Ma) and the gradual decline from the Cretaceous (145.5–65.5 Ma) onwards have been linked to the spread of deeply rooted trees and the rise of angiosperms, respectively. But this paradigm overlooks the coevolution of roots with the major groups of symbiotic fungal partners that have dominated terrestrial ecosystems throughout Earth history. The colonization of land by plants was coincident with the rise of arbuscular mycorrhizal fungi (AMF), while the Cenozoic (c. 65.5–0 Ma) witnessed the rise of ectomycorrhizal fungi (EMF) that associate with both gymnosperm and angiosperm tree roots. Here, we critically review evidence for the influence of AMF and EMF on mineral weathering processes. We show that the key weathering processes underpinning the current paradigm and ascribed to plants are actually driven by the combined activities of roots and mycorrhizal fungi. Fuelled by substantial amounts of recent photosynthate transported from shoots to roots, these fungi form extensive mycelial networks which extend into soil actively foraging for nutrients by altering minerals through the acidification of the immediate root environment. EMF aggressively weather minerals through the additional mechanism of releasing low molecular weight organic chelators. Rates of biotic weathering might therefore be more usefully conceptualized as being fundamentally controlled by the biomass, surface area of contact, and capacity of roots and their mycorrhizal fungal partners to interact physically and chemically with minerals. All of these activities are ultimately controlled by rates of carbon‐energy supply from photosynthetic organisms. The weathering functions in leading carbon cycle models require experiments and field studies of evolutionary grades of plants with appropriate mycorrhizal associations. Representation of the coevolution of roots and fungi in geochemical carbon cycle models is required to further our understanding of the role of the biota in Earth's CO2 and climate history.
Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes*

The cellular and molecular basis of growth hormone (GH) actions on the heart remain poorly defined, and it is unclear whether GH effects on the myocardium are direct or mediated at least in part via insulin-like growth factor (IGF-1). Here, we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate model to study the effects of GH because of artifactual loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR. Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt intracellular pathways in the cells expressing GHR. Although exposure to GH resulted in a significant increase in the size of the cardiomyocyte and increased expression of c-fos, myosin light chain 2, and skeletal α-actin mRNAs, there were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in response to GH stimulation. In this model, GH increased incorporation of leucine, uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In contrast, GH decreased uptake of 2-deoxy-d-glucose and levels of Glut1 protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in cellular metabolic profile in the absence of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be independent of IGF-1.
HBV Infection in Patients With End-Stage Renal Disease

Controlling the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major triumphs in the management of end-stage renal disease. However, HBV incidence and prevalence rates remain high in dialysis patients in less-developed countries, and HBV within dialysis units continues to spread in the industrialized world. Overall response rates to HBV vaccination are lower in dialysis patients than in the nondialysis population. Lamivudine is effective in the treatment of HBV infection in the dialysis setting. Presence of hepatitis B surface antigen (HbsAg) has a negative impact on patient survival after renal transplantation. Several issues remain unanswered with regard to the management of HBV infection in dialysis patients, including the management of lamivudine resistance and the optimal timing and duration of antiviral therapy. Liver biopsy prior to renal transplantation is crucial in order to identify and exclude patients with advanced fibrosis or even cirrhosis.