Miracle-dz/UniFAR-FTUs huggingface dataset:
The ZnuABC high‐affinity zinc uptake system and its regulator Zur in Escherichia coli

In Escherichia coli, lacZ operon fusions were isolated that were derepressed under iron repletion and repressed under iron depletion. Two fusions were localized in genes that formed an operon whose gene products had characteristics of a binding protein‐dependent transport system. The growth defect of these mutants on TY medium containing 5 mM EGTA was compensated for by the addition of Zn2+. In the presence of 0.5 mM EGTA, only the parental strain was able to take up 65Zn2+. This high‐affinity transport was energized by ATP. The genes were named znuACB (for zinc uptake; former name yebLMI ) and localized at 42 min on the genetic map of E. coli. At high Zn2+ concentrations, the znu mutants took up more 65Zn2+ than the parental strain. The high‐affinity 65Zn2+ uptake was repressed by growth in the presence of 10 μM Zn2+. A znuA–lacZ operon fusion was repressed by 5 μM Zn2+ and showed a more than 20‐fold increase in β‐galactosidase activity when Zn2+ was bound to 1.5 μM TPEN [tetrakis‐(2‐pyridylmethyl) ethylenediamine]. To identify the Zn2+‐dependent regulator, constitutive mutants were isolated and tested for complementation by a gene bank of E. coli. A complementing gene, yjbK of the E. coli genome, was identified and named zur (for zinc uptake regulation). The Zur protein showed 27% sequence identity with the iron regulator Fur. High‐affinity 65Zn2+ transport of the constitutive zur mutant was 10‐fold higher than that of the uninduced parental strain. An in vivo titration assay suggested that Zur binds to the bidirectional promoter region of znuA and znuCB.
Bröcker , Johannes ; Korzhenevych , Artem Working Paper Forward looking dynamics in spatial CGE modelling

This paper sets up a multiregional dynamic framework by combining the optimal savings model with investment adjustment costs and the spatially disaggregated model with Dixit-Stiglitz structure in the modern sector. Because of increasing product diversity on the dynamic equilibrium path, the model belongs to the category of semi-endogenous growth models. The distinction of goods, factors, firms, and households by location, and the incorporation of trade costs in the model allow to study a variety of issues in regional and transport economics. We describe the model calibration and a taylor-made solution algorithm. The functionality is demonstrated using two illustrative examples.
Downregulation of transcription factor AP-2 predicts poor survival in stage I cutaneous malignant melanoma.

PURPOSE The transcription factor, activator protein (AP)-2, a 52-kd DNA-binding protein, is suggested to inhibit tumor growth through the activation of p21. To test this hypothesis, we analyzed AP-2 and p21 protein expressions in stage I cutaneous malignant melanomas to clarify their significance with regard to tumor progression and survival. PATIENTS AND METHODS A consecutive series of 369 clinical stage I cutaneous malignant melanoma patients were investigated using immunohistochemistry. The detected expression levels were correlated with each other, with clinicopathologic data, and with melanoma survival. RESULTS The loss of AP-2 expression was significantly associated with low p21 expression (P=.007), high tumor thickness (P=.001), high Clark's level (P=.046), high tumor-node-metastasis (TNM) category (P=.006), recurrent disease (P=.001), and male sex (P=.03). Tumor thickness, Clark's level, TNM category, bleeding, AP-2 index, and sex were all important predictors of both recurrence-free survival (RFS) and overall survival (OS) of melanoma in this order. In Cox's multivariate analysis, high tumor thickness (P=.0001), low AP-2 index (P=.0153), and bleeding (P=.0143) predicted poor RFS. Poor OS was predicted by high tumor thickness (P=.0008) and bleeding (P=.0092). CONCLUSION The loss of AP-2 expression seems to be associated with malignant transformation and tumor progression in cutaneous malignant melanoma. This tumor-suppressive action of AP-2 may be mediated through p21 regulation. Furthermore, decreased AP-2 expression is independently associated with elevated risk of subsequent metastatic behavior of stage I cutaneous malignant melanoma.
Integrating Palliative Care: A Postmodern Perspective

Hospice and palliative care philosophy is becoming increasingly incorporated into medical practice, education, and research. However, this process of integration may be hindered by continued adherence to several perceived conceptual dichotomies: natural and medicalized death, research and clinical care, and acceptance and denial of dying. These dichotomies were perhaps essential for the initial development of palliative care but could undermine the continuing evolution of care for the terminally ill. In this article, the authors deconstruct these dichotomies and advocate for a fully integrated model of palliative care.
Can E. coli or thermotolerant coliform concentrations predict pathogen presence or prevalence in irrigation waters?

Abstract An increase in food-borne illnesses in the United States has been associated with fresh produce consumption. Irrigation water presents recognized risks for microbial contamination of produce. Water quality criteria rely on indicator bacteria. The objective of this review was to collate and summarize experimental data on the relationships between pathogens and thermotolerant coliform (THT) and/or generic E. coli, specifically focusing on surface fresh waters used in or potentially suitable for irrigation agriculture. We analyzed peer-reviewed publications in which concentrations of E. coli or THT coliforms in surface fresh waters were measured along with concentrations of one or more of waterborne and food-borne pathogenic organisms. The proposed relationships were significant in 35% of all instances and not significant in 65% of instances. Coliform indicators alone cannot provide conclusive, non-site-specific and non-pathogen-specific information about the presence and/or concentrations of most important pathogens in surface waters suitable for irrigation. Standards of microbial water quality for irrigation can rely not only on concentrations of indicators and/or pathogens, but must include references to crop management. Critical information on microbial composition of actual irrigation waters to support criteria of microbiological quality of irrigation waters appears to be lacking and needs to be collected.
Dissociable Brain Activation Responses to 5-Hz Electrical Pain Stimulation: A High-field Functional Magnetic Resonance Imaging Study

BackgroundTo elucidate neural correlates associated with processing of tonic aching pain, the authors used high-field (3-T) functional magnetic resonance imaging with a blocked parametric study design and characterized regional brain responses to electrical stimulation according to stimulus intensity–response functions. MethodsPain was induced in six male volunteers using a 5-Hz electrical stimulus applied to the right index finger. Scanning sequences involved different levels of stimulation corresponding to tingling sensation (P1), mild pain (P2), or high pain (P3). Common effects across subjects were sought using a conjunction analyses approach, as implemented in statistical parametric mapping (SPM-99). ResultsThe contralateral posterior/mid insula and contralateral primary somatosensory cortex were most associated with encoding stimulus intensity because they showed a positive linear relation between blood oxygenation level–dependent signal responses and increasing stimulation intensity (P1 < P2 < P3). The contralateral secondary somatosensory cortex demonstrated a response function most consistent with a role in pain intensity encoding because it had no significant response during the innocuous condition (P1) but proportionally increased activity with increasingly painful stimulus intensities (0 < P2 < P3). Finally, a portion of the anterior cingulate cortex (area 24) and supplementary motor area 6 demonstrated a high pain–specific response (P3). ConclusionsThe use of response function modeling, conjunction analysis, and high-field imaging reveals dissociable regional responses to a tonic aching electrical pain. Most specifically, the primary somatosensory cortex and insula seem to encode stimulus intensity information, whereas the secondary somatosensory cortex encodes pain intensity information. The cingulate findings are consistent with its proposed role in processing affective–motivational aspects of pain.
Identification of G proteins in lacrimal gland.

PURPOSE The intent of this study was to identify and characterize guanine nucleotide binding proteins (G proteins) that are a component of cell signaling of stimulus-secretion coupling in lacrimal gland. METHODS Membranes were isolated from the lacrimal glands of male Sprague-Dawley rats and New Zealand rabbits and were used to identify G proteins in lacrimal gland by Western blot analysis. Solubilized membrane proteins from lacrimal glands and from a positive tissue control (SH-SY5Y cells) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The alpha subunits of the G proteins were identified by immunoreactivity, with specific peptide directed antisera against Gs alpha, Gi alpha 1, Gi alpha 1/2, and Go alpha. The initial characterization of coupling of specific G proteins to receptors was accomplished by preincubation of membranes with nonimmune serum, anti-Gs alpha, or anti-Go alpha antiserum and assay of adenylyl cyclase activity in the presence of the neuropeptide, vasoactive intestinal peptide (VIP), or forskolin. RESULTS Gs alpha, Gi alpha 3, and Go alpha were present in all three membrane preparations. Gs alpha subunits were detected as two bands at 45 to 48 kd and 48 to 54 kd. Gi alpha 3 was detected as a single protein at 40 to 41 kd, and at least one form of Go alpha with a molecular weight of 40 kd was detected in all three preparations. Gi alpha 1 was detected in immunoblots of rat lacrimal and SH-SY5Y membranes at 41 kd, and the density of the band was enhanced in blots probed with anti-Gi alpha 1/2 antiserum. Immunoreactivity to anti-Gi alpha 1 or anti-Gi alpha 1/2 was faint or not detectable in rabbit lacrimal membranes. A prominent band was detected in rabbit and rat lacrimal but not in SH-SY5Y membranes at 31 kd with anti-Gi alpha 1/2 antiserum, which may represent a G protein involved in exocytosis. Coupling of VIP receptor activation to adenylyl cyclase by Gs alpha was evidenced by the reduction of VIP stimulation of the enzyme by preincubation of rabbit membranes with anti-Gs alpha antiserum. In contrast, preincubation of membranes with anti-Go alpha antiserum resulted in an increase in activity of adenylyl cyclase in the presence of VIP. CONCLUSIONS Detection of specific alpha subunits in lacrimal gland indicates that Gs, Gi, and Go are present in rabbit and rat lacrimal gland. Both Gs and Go influence VIP stimulation of lacrimal adenylyl cyclase and thus are presumed to be involved in signal transduction, leading to second-messenger accumulation and subsequent regulation of lacriminal function, including secretion. In addition, an unidentified protein is present in lacrimal gland that may represent one of the guanine nucleotide binding proteins involved in exocytosis.
Inhibitors of nitric oxide synthase induce larval settlement and metamorphosis of the polychaete annelid Capitella teleta

The neurotransmitter nitric oxide (NO) has been implicated in the inhibitory control of metamorphosis of some marine gastropods, echinoderms, and ascidians. We have explored whether or not metamorphosis of metatrochophore larvae of the polychaete annelid Capitella teleta is also regulated by NO. Immunohistochemical analysis revealed a bilateral group of three large nitric oxide synthase (NOS) immunoreactive cells that lie dorsal to the pharynx and extend ventral processes toward the pharynx in the region of the dorsal pharyngeal pad. Smaller NOS-immunoreactive cells were distributed widely throughout the body but concentrated in the prostomium and pygidium. Histological analysis for NO, using the NO detector diaminofluorescein-FM, showed that NO concentration was high in the larval midgut, although diffuse amounts of NO were detected throughout the body. Inhibitors of NOS, including s-methylisothiourea sulfate, aminoguanidine hemisulfate, 7-nitroindazole, and N-methyl-L-arginine all induced settlement and metamorphosis of the Capitella larvae in a concentration-dependent manner. The NO donor nitroprusside prevented the induction of settlement and metamorphosis induced by the NOS inhibitor N-methyl-L-arginine, but did not prevent settlement and metamorphosis induced by a marine sediment extract, exogenous serotonin, or by the serotonin reuptake inhibitor fluoxetine. Pre-incubating larvae with the serotonin receptor antagonist ketanserin also inhibited settlement and metamorphosis in response to NOS inhibitors. These results suggest that endogenous production of NO maintains the larval state in C. teleta, and that endogenous serotonin stimulates metamorphosis in a way similar to that described previously for larvae from other major invertebrate phyla.
The pregnane X receptor in tuberculosis therapeutics

Introduction: Among the infectious diseases, tuberculosis (TB) remains the second most common cause of death after HIV. TB treatment requires the combination of multiple drugs including the rifamycin class. However, rifamycins are activators of human pregnane X receptor (PXR), a transcription factor that regulates drug metabolism, drug resistance, energy metabolism and immune response. Rifamycin-mediated PXR activation may affect the outcome of TB therapy. Areas covered: This review describes the role of PXR in modulating metabolism, efficacy, toxicity and resistance to anti-TB drugs; as well as polymorphisms of PXR that potentially affect TB susceptibility. Expert opinion: The wide range of PXR functions that mediate drug metabolism and toxicity in TB therapy are often underappreciated and thus understudied. Further studies are needed to determine the overall impact of PXR activation on the outcome of TB therapy.
Growth and plasma zinc responses of young pigs fed pharmacologic levels of zinc.

Three trials were conducted to evaluate high levels of Zn addition from various Zn sources on growth performance and plasma Zn responses of 8-kg pigs. Zinc supplements were added to 20% CP starting diets (125 mg of Zn/kg) containing antibiotics. Trial 1 was done to evaluate plasma Zn responses of pigs fed three different feed-grade Zn sources: ZnO where supplemental Zn levels were 0, 250, 500, 1,000, 3,000, and 5,000 mg/kg; ZnSO4 at 1,500 or 2,500 mg of Zn/kg; and a zinc-lysine complex (Zn-Lys) at 1,500 or 2,500 mg of Zn/kg. Plasma Zn concentration as a function of supplemental Zn intake was fitted to a broken-line for ZnO data and to simple linear models for ZnSO4 and Zn-Lys data. For ZnO, plasma Zn did not increase until concentrations > 1,000 mg Zn/kg were fed. Above this level, plasma Zn increased linearly (P < .01) for all three sources of Zn, although slopes of the ZnO and Zn-Lys response curves were 56% (P < .05) and 110%, respectively, of the ZnSO4 slopes. In Trial 2, five diets were fed: basal, 3,000 and 5,000 mg of Zn/kg from ZnO, and 3,000 and 5,000 mg of Zn/kg from ZnSO4. Daily gain and daily feed intake were increased (P < .05) by ZnO addition, regardless of level, whereas ZnSO4 addition increased these performance indices only at the 3,000 mg of Zn/kg level of supplementation. Plasma Zn responses to ZnSO4 addition were almost double those of ZnO addition. (ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy and Tolerability in Migraine Prophylaxis of Flunarizine in Reduced Doses: A Comparison with Propranolol 160 Mg Daily

This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d. = FLU 10 mg and 5 mg o.d. = FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n = 58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P< 0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P< 0.001) and showed a trend for noninferiority of FLU5 and propranolol (P = 0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe.
Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow.

BACKGROUND Induction of donor-specific tolerance to tissue or organ allografts can readily be achieved by administration of allogeneic bone marrow to neonatal rodents; however, in adult recipients induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning. Described here is a novel method of promoting transplantation tolerance that involves inoculation of donor bone marrow into the thymus of transiently immunosuppressed adult recipients. METHODS Prospective Wistar-Furth recipients were inoculated with allogeneic Lewis bone marrow cells (BMCs) either intrathymically or intravenously in conjunction with a single dose of antilymphocyte serum 2 to 3 weeks before receiving donor-strain cardiac allografts. Recipients were monitored for graft survival and examined for presence of hematopoietic chimerism. RESULTS Intrathymic but not intravenous inoculation of donor BMCs led to permanent survival of donor-strain cardiac allografts, whereas third-party Dark agouti cardiac allografts were rejected promptly. Persistence of donor chimerism was demonstrated in the thymus of Wistar-Furth recipients of intrathymic Lewis BMCs for as long as 3 weeks after BMC inoculation. CONCLUSIONS Intrathymic inoculation of BMCs concurrently with a single dose of antilymphocyte serum induces donor-specific unresponsiveness to rat cardiac allografts. The unresponsiveness may be the result of deletion or functional inactivation of alloreactive clones maturing in a thymus bearing donor alloantigen. Intrathymic inoculation of BMCs deserves further evaluation as a possible clinical strategy for the induction of transplantation tolerance.
Revenue Management with Correlated Demand Forecasting

Many airlines are struggling to survive in today's economy. A crucial contribution to the success of an airline is an e cient management of its revenues. The problem underlying revenue management is for the airline to decide whether to accept customer requests for air travel on a real time basis in order to maximize its expected revenue. Typically, an airline o ers several products (itinerary and fare class combinations) and operates a network of many resources (class cabin in a given ight). Demand forecasting is a crucial component of airline revenue management. Most of the papers in this area consider univariate demand which is then modelled with a statistical distribution, the normal and gamma distributions being the most popular (McGill and van Ryzin 1999; Lee 1990). However, in practice the available capacity is allocated dynamically between di erent products and thus is makes sense to take into account the potential correlations among product demand. At the same time, demand for any single product is recorded over the entire booking horizon at xed time points (snapshots). In this framework it is natural to investigate whether there is correlation among realizations of demand for any individual product in di erent booking periods. Inter product and inter temporal correlations of demand have been documented empirically (McGill 1995). For e ciency reasons, it is therefore important to take them into account in a demand forecasting model.
Normotensive scleroderma renal crisis with diffuse alveolar damage after corticosteroid therapy

A 68-year-old woman with systemic sclerosis developed acute respiratory failure due to diffuse alveolar hemorrhage and normotensive scleroderma renal crisis (SRC) shortly after the initiation of corticosteroid therapy. Treatment with angiotensin-converting enzyme inhibitor and plasmapheresis had failed in this patient. Autopsy showed diffuse alveolar damage and thrombotic micro-angiopathy. The sequence of events in this patient clarifies the pathologic process of normotensive SRC, and suggests a causative role of corticosteroid therapy and normotensive SRC.
Development of Autoimmune Diabetes in the Absence of Detectable IL-17A in a CD8-Driven Virally Induced Model

Recent studies have shown that IL-17 can contribute beneficially to pathogen defense but also that excessive IL-17 levels are associated with chronic inflammation and autoimmune disorders. To date, the role of IL-17 in viral infections and type 1 diabetes is ambiguous. In this study, we used IL-17A enhanced green fluorescent protein bicistronic reporter mouse strains to analyze in situ production of IL-17A. Upon Klebsiella pneumoniae bacterial infection, CD4+ and γδ T cells produce IL-17A. In contrast, CD4+ or CD8+ T cells do not produce IL-17A in response to acute or protracted viral infection with lymphocytic choriomeningitis virus or during autoimmune diabetes development in the CD8-driven lymphocytic choriomeningitis virus-induced model of type 1 diabetes. We conclude that viral elimination and type 1 diabetes can occur in the absence of detectable IL-17A production, suggesting IL-17A is not essential in these settings.