Miracle-dz/UniFAR-FTUs huggingface dataset:
Coxiella burnetii Survival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-γ Mediates its Restoration and Bacterial Killing1

The subversion of microbicidal functions of macrophages by intracellular pathogens is critical for their survival and pathogenicity. The replication of Coxiella burnetii, the agent of Q fever, in acidic phagolysosomes of nonphagocytic cells has been considered as a paradigm of intracellular life of bacteria. We show in this study that C. burnetii survival in THP-1 monocytes was not related to phagosomal pH because bacterial vacuoles were acidic independently of C. burnetii virulence. In contrast, virulent C. burnetii escapes killing in resting THP-1 cells by preventing phagosome maturation. Indeed, C. burnetii vacuoles did not fuse with lysosomes because they were devoid of cathepsin D, and did not accumulate lysosomal trackers; the acquisition of markers of late endosomes and late endosomes-early lysosomes was conserved. In contrast, avirulent variants of C. burnetii were eliminated by monocytes and their vacuoles accumulated late endosomal and lysosomal markers. The fate of virulent C. burnetii in THP-1 monocytes depends on cell activation. Monocyte activation by IFN-γ restored C. burnetii killing and phagosome maturation as assessed by colocalization of C. burnetii with active cathepsin D. In addition, when IFN-γ was added before cell infection, it was able to stimulate C. burnetii killing but it also induced vacuolar alkalinization. These findings suggest that IFN-γ mediates C. burnetii killing via two distinct mechanisms, phagosome maturation, and phagosome alkalinization. Thus, the tuning of vacuole biogenesis is likely a key part of C. burnetii survival and the pathophysiology of Q fever.
Distributed adaptive routing for spidergon NoC

Spidergon is a popular NoC (Network-On-Chip) developed to realize cost effective multi-processor SoC (MPSoC) using a fixed optimized topology [1]. Increasing diversity of applications, quality of service requirements and deterministic routing schemes inhibit the performance by creating congestion bottlenecks. This paper presents an adaptive routing algorithm that exploits the path diversity of spidergon NoC and selects the optimal path on the basis of congestion level (CL). CL depicts current traffic conditions. Proposed scheme is compared with native deterministic routing schemes of spidergon NoC i.e. aFirst and aLast. Experimental results demonstrate that our algorithm distributes traffic evenly while reducing hot-spots resulting in a considerable performance improvement.
Effect of ZnCl2 and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

Purpose: NiCl2 (15 µM) enhances the ERG b-wave amplitude of vertebrate retina, up to 1.5-fold by blocking E/R-type voltage-gated Ca2+ channels, which is mediated by blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may be involved in the modulation of retinal signalling. Therefore, we tested the effect of both, ZnCl2 (10 to 500 µM) and DEDTC (100 to 500 µM), which chelates zinc ions for the capacity to influence the ERG b-wave amplitude. Methods: Transretinal potentials from the isolated bovine retina were recorded as electroretinograms and Ca2+ inward currents by patch-clamp recordings of stably Cav2.3 transfected HEK-293 cells, yielding an IC50 value of 5.3 µM for ZnCl2. Results: ZnCl2 (10–15 µM) increased the b-wave amplitude by 1.52-fold ± 0.12 (n = 6 retinas), which was partially reversible upon washout. The same 1.5-fold stimulation of the b-wave amplitude was reported recently for 15 µM NiCl2. The superfusion of isolated retinas by DEDTC (100 µM) caused a transient decrease of the ERG b-wave amplitude (0.75-fold ± 0.06; n = 4), suggesting that the co-secretion of Zn2+ ions may occur under scotopic conditions. Conclusion: The stimulatory effect of ZnCl2 on the ERG b-wave amplitude resembles the stimulatory effect of NiCl2 and may be mediated rather by the NiCl2-sensitive, Cav2.3 E-/R-type voltage-gated Ca2+ channels than by NiCl2-sensitive T-type channels.
Sensory lateralization in pain subjective perception for noxious heat stimulus

The aim of the present study was to identify and characterize hemispheric lateralization for pain intensity perception. A sample of 351 healthy volunteers was tested by the immersion of the right hand for 10 s followed by the same test for the left hand (RL group; n = 199) or in a random sequence (RND group; n = 152) into a water bath (48°C, 15 s). Pain intensity was self-reported by the Visual Analogue Scale (VAS). The motor hemispherical Lateralization Index (LI) was obtained by the Edinburgh Inventory. Gender, hand skin fold, interstimulus time and menstrual cycle data in case of female subjects were recorded. The sample, 60.7% females and 39.3% males, 20.4 - 0.18 (mean - SEM) years old, showed 92.1% right-handed subjects. Left hand VAS was significantly higher than right hand VAS for RL (7.24 - 1.31 vs 6.74 - 1.52; p < 0.01) and RND (7.24 - 0.82 vs 6.73 - 1.25; p < 0.01) both for right- and left-handed subjects. A low but significant correlation for VAS scores and LI was found ( r = 0.14; p < 0.05 or r = 0.18; p < 0.05, for left or right hand, respectively). Skin fold was statistically similar in both hands ( p > 0.05) being highly correlated with each other ( r = 0.68; p < 0.05). Pain subjective perception was not correlated to interstimulus time ( r = -0.01; p > 0.05). Females showed significantly higher values than males for both left and right hand VAS scores. Periovulatory phase VAS value was significantly higher than luteal phase VAS only for the right hand test (7.57 - 0.20 vs 6.47 - 0.33; p < 0.01). The results of the present study suggest a lateralization of pain intensity perception to the right hemisphere not correlated with the motor hemispheric lateralization.
Mannitol Challenge Does Not Confirm Bronchial Hyperreactivity in Some Histamine-Responsive Asthmatic Children

Objective. The aim of this study was to compare the usefulness of mannitol provocation test to that of classical histamine challenge in children with PC20FEV1 histamine lower than 4 mg/ml. Methods. Twenty-two adolescent patients (mean age of 15.4 ± 4.1 years) with established asthma (PC20FEV1 histamine below 4 mg/ml) were included in this study. Bronchial challenge with mannitol was performed 1–2 days after the test with histamine. Results. The fraction of positive results of mannitol test was markedly lower when compared with the histamine challenge (72.7% vs. 100%, p = .015). The test was discontinued in one case due to severe coughing after inhalation of 315 mg of mannitol. Coughing during inhalation of dry mannitol powder occurred in most patients, although drinking water after subsequent doses alleviated this symptom in nearly all of them. Of note, triboelectrification of the inhaler and capsules was observed during the administration of consecutive mannitol doses, markedly hindering the delivery of this provoking agent. The relative decrease in FEV1 resulting from bronchial provocation was significantly lower following mannitol delivery when compared with the histamine test (70.3% vs. 81.6% of resting value, p < .001). Significant correlation was not observed between the values of PC20FEV1 histamine and PD15FEV1 mannitol levels. Conclusions. Bronchial challenge with mannitol can be used as a screening test in everyday practice, but one cannot exclude bronchial hyperresponsiveness based on its negative results. Moreover, its usefulness is limited by the influence of static on the delivery of sequential mannitol doses and coughing which can be often associated with mannitol inhalation.
An Unconditional Quantile Analysis of the Determinants of Self-Employed Income across Regional Economies: An Initial Assessment

Supporters claim entrepreneurship is critical to building and sustaining regional economies in both urban and rural areas. Proponents argue that economic development practices that support entrepreneurship are essential because they cultivate innovation which, in turn, creates new jobs, new wealth, and a better quality of life. However, real self-employed per capita income has decreased over the last decade in the three states examined here. This downward trend highlights the need to examine the drivers of entrepreneurial income. The income of self-employed workers is critical to economic development because a major goal of economic policy is to increase incomes not just employment. Identifying and quantifying the personal, cultural, and regional (especially agglomerative) economic factors that influence self-employed income provides policy makers with another tool to enhance economic development efforts. This study uses data from the American Community Survey for three states (Georgia, North Carolina, and South Carolina) in ordinary and unconditional quantile regressions to investigate relationships between individual entrepreneurial income and (1) individual personal attributes, (2) social/institutional assets available to the entrepreneur, and the (3) regional economic environment. Personal attributes, such as education and gender, and the importance of self-employed income to total family income partially explain self-employment income variation. We test for the positive impact of agglomerative effects through lagged per capita income, metropolitan status, and concentration of financial services. We also test the hypothesis that agglomerative effects are greater for higher levels of self-employed income. Results support a generally positive relationship between the agglomerative variables and self-employed income and the hypothesis that agglomerative type effects are stronger for individuals with higher self-employed income.
Yeast Sequencing Reports

We have isolated a mutant which exhibits partial constitutivity for a-specific gene expression in a cells. The wild-type gene was cloned and demonstrated to be allelic to the STE13 gene, which encodes the dipeptidyl aminopeptidase involved in processing of the a-factor prepropheromone. Thus, the mating defect of the stel3 mutations in a cells may result both from the production of incompletely processed a-factor and from the increased expression of a-specific genes. The STE13 open reading frame of 931 amino acids contains a putative membrane-spanning segment near its amino terminus and is 31% identical to a second yeast dipeptidyl aminopeptidase (DAP2). A null mutant of STEl3 has been constructed: it is viable and sporulation-proficient. The sequence has been deposited in the GenBank data library under Accession Number L21944.
Backpropagation learning algorithm with different learning coefficients for each layer

When considering the algorithm of error backpropagation learning, it is seen that the learning of each layer is not completed independently. This paper proposes a DLBP learning algorithm which uses different learning coefficients for each layer. By changing the ratio of the learning coefficients, the following can be controlled: • the learning progress of the hidden units; • the influence of the hidden units on the network. With DLBP learning, we can construct the corresponding networks to the different requirement such as; • to obtain a network with small number of hidden units; and • to obtain a fault tolerant network.
Cancer procoagulant in patients with adenocarcinomas

Cancer procoagulant (CP) is a cysteine proteinase that may be produced by malignant and foetal tissue. The possible role of CP in the pathogenesis of cancer-related thrombosis has been suggested recently. The purpose of the study was to evaluate coagulation prothrombotic markers and their relation to CP concentration in the blood of patients with gastrointestinal adenocarcinomas (GIAC). The study group consisted of 45 patients with confirmed diagnosis of adenocarcinoma (stomach, 18 patients; colon, 27 patients) and without evident metastatic disease. In 24 patients further observation showed metastases. The control group for CP was composed of 10 healthy subjects. Blood samples were drawn on the admission day, before any treatment. Among 45 patients with GIAC, deep venous thrombosis was observed in two (4.4%). In all patients the CP activity in the serum was found, and the mean CP activity shortened the coagulation time almost three times compared with the healthy control group. Also, the mean thrombin–antithrombin complex concentration was above the normal range. A significant elevation of the mean prothrombin fragment 1+2 plasma content in this group of patients was noticed. Despite these observations, CP remained within the normal range and did not correlate with thrombin–antithrombin complex or prothrombin fragment 1+2 plasma concentrations. A positive correlation was observed between serum CP and fibrinogen concentration, and a negative correlation between CP and free protein S plasma content (P = 0.04 and P = 0.025, respectively). A negative correlation between activated protein C resistance ratio and protein C activity in the plasma was confirmed. Protein C activity in the plasma showed a correlation with free protein S plasma content. Analysis of factors influencing the activated partial thromboplastin time revealed the presence of antiphospholipid antibodies in seven persons from the study group (in three cases of IgG and in four cases of IgM class). Our data suggest that CP is a minor risk factor for deep venous thrombosis in GIAC patients. To confirm this, however, the number of patients and controls should be larger. After 3 years of observation, the follow-up in 10 living GIAC patients showed nobody with thromboembolic disease.
Transient tachypnea of the newborn: what is new?

An infant born by cesarean delivery is at risk of having excessive pulmonary fluid which makes predisposition to transient tachypnea of the newborn (TTN), because fetal thorax compression during labor leads to the loss of large volumes liquid from the lungs. At birth, the pulmonary epithelium switches from predominantly facilitated Cl− secretion to predominantly active Na+ reabsorption with the increase expression epithelial Na+-channels (ENaC). Diminished activity or immaturity of this process may contribute to the development of TTN. Familial clustering of some TTN cases shows a genetic predisposition in the developing of this disorder. Antenatal glucocorticoids induce lung Na+ reabsorption by increasing the number and activity of channels even in hypoxia. Since a large release of fetal adrenaline occurs late in labor stimulating ENaC to start reabsorbing lung fluids, aerolized β-agonists may be used in the treatment. Genetic predisposition for β-adrenergic hyporesponsiveness may cause TTN in newborn period, and asthma/wheezing in older age groups. Although furosemide accelerates lung fluid resorption and cause pulmonary vasodilatation, oral or aerosolized furosemide cannot be recommended as treatment for TTN unless additional data become available.
Formation of tissue factor–factor VIIa–factor Xa complex promotes cellular signaling and migration of human breast cancer cells

Summary. Tissue factor (TF) is a transmembrane glycoprotein that initiates blood coagulation when complexed with factor (F)VIIa. Recently, TF has been shown to promote cellular signaling, tumor growth, angiogenesis, and metastasis. In the present study, we examined the pathway by which TF–FVIIa complex induces cellular signaling in human breast cancer cells using the Adr‐MCF‐7 cell line. This cell line has high endogenous TF expression as measured by flow cytometry and expression of protease‐activated receptors 1 and 2 (PAR1 and PAR2) as determined by reverse transcriptase‐polymerase chain reaction analysis. Both PAR1 and PAR2 are functionally active as determined by induction of p44/42 mitogen‐activated protein kinase (MAPK) phosphorylation using specific agonist peptides. We found that MAPK phosphorylation in this cell line was strongly induced by the combination of FVIIa and factor (F)X, but not by FVIIa alone at a concentration of FVIIa that approaches physiological levels. Induction of MAPK phosphorylation involved the formation of TF–FVIIa–FXa complex and occurred by a pathway that did not require thrombin formation, indicating a critical role for FXa generation. In addition, induction of MAPK phosphorylation was found to be independent of PAR1 activation. We then examined whether TF–FVIIa complex formation could promote tumor cell migration using a modified Boyden chamber chemotaxis assay. The combination of FVIIa and FX, but not FVIIa alone, strongly induced migration of tumor cells by a pathway that probably involves PAR2, but not PAR1 activation. MAPK phosphorylation was found to be required for the induction of cell migration by the combination of FVIIa and FX. These data suggest that TF–FVIIa‐mediated signaling in human breast cancer cells occurs most efficiently by formation of the TF–FVIIa–FXa complex. One of the physiological consequences of this signaling pathway is enhanced cell migration that is probably mediated by PAR2, but not PAR1 activation.
Antisense oligonucleotide specific for transforming growth factor-beta 1 inhibit both in vitro and in vivo growth of MBT-2 murine bladder cancer.

INTRODUCTION AND OBJECTIVES TGF-beta is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-beta by malignant cells may be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In this study, we used a TGF-beta producing C3H/He-MBT-2 murine bladder tumor model to investigate the feasibility of antisense oligonucleotide (ODN) gene therapy strategy to block the production of TGF-beta from tumor cells and evaluate its influence on both in vitro tumor growth and in vivo tumor formation. MATERIALS AND METHODS Using a plasmid, pRUFCD, we constructed a recombinant plasmid pRUFCD/TGF-beta 1(-) containing antisense TGF-beta ODN and then transfected in into MBT-2 cells by electroporation. Three transfectant clones were successfully obtained by their resistance to 5-fluorouracil and cytosine. RESULTS The secretion of TGF-beta from the three obtained TGF-beta antisense-blocked MBT-2 cell clones, as assessed by ELISA, were all decreased. Moreover, they all exhibited smaller colony size in the in vitro anchorage-independent soft agar colony forming assay. Tumor growths in mice injected with these three clones were all inhibited compared with those injected with parental tumor cells. CONCLUSION This study demonstrates that after reducing the secretion of TGF-beta 1 on tumor cells by TGF-beta 1 antisense, ODN can inhibit their in vitro growth and in vivo tumor formation suggesting that this approach can be a potentially useful strategy to abolish the adverse immunosuppression effect of TGF-beta 1 producing autologous tumor vaccine and therefore to enhance host antitumor immune response.
Association of a Polymorphic Variant of the Adiponectin Gene with Insulin Resistance in African Americans

Hypertension, type 2 diabetes, and obesity are common complex disorders that contribute to cardiovascular (CV) disease. Insulin resistance increases CV risk and is present in these disorders. Adiponectin, a protein secreted by adipocytes with metabolic and vascular protective effects, is lower in obesity and insulin resistance. Several single nucleotide polymorphisms (SNP) have been identified in the adiponectin (ADIPOQ) gene. Associations of ADIPOQ polymorphisms with diabetes and obesity have been described in Caucasians and Asians. The purpose of this study was to determine if genetic variants of ADIPOQ are associated with insulin resistance and CV risk in African Americans. Metabolic traits (lipids, glucose, insulin, and insulin sensitivity) and blood pressure were measured in 273 African Americans. DNA was examined by DNA sequence analysis and SNPs of candidate genes including ADIPOQ were studied. Statistica analyses were performed by regression of the quantitative trait phenotypes on the groups defined by the SNP genotypes, adjusting for age, sex, and body mass index (BMI). SNP 712 (rs3774261) ofthe/lD/POQgene showed significant association with insulin resistance (p= 0.001). Despite the relatively small sample, our results indicate that genes that regulate adipocyte function may have a regulatory role in the expression of metabolic traits in obesity‐associated chronic disease.
The macroeconomic impact of news about policy and news about the economy in ECB announcements

Central bank announcements simultaneously convey information about monetary policy and the economic outlook. We use changes in interest rate expectations and stock prices around the time of policy announcements to disentangle the impact of news about monetary policy from that of news about the economic outlook. We find that both play a significant role in the dynamics of inflation and economic growth, and that controlling for news about the economy helps us to measure more accurately the transmission of monetary policy. JEL Classification: E32, E52, E58
Efficacy of intravesical ropivacaine injection on urinary symptoms following ureteral stenting: a randomized, controlled study.

PURPOSE Previous studies suggest that intravesical administration of nonsteroidal anti-inflammatory drugs may reduce the troublesome voiding symptoms and pain related to ureteral stenting. The objective of this study was to investigate the effectiveness of a long-acting local anesthetic, ropivacaine, injected submucosally into the bladder to control ureteral stent-associated symptoms. MATERIALS AND METHODS A randomized, single-blinded, study approved by our Institutional Review Board of adult patients scheduled for ureteroscopic stone surgery and possible stent placement was conducted. Patients were randomized to either the treatment cohort, who received five injections of 2 mL 0.5% ropivacaine around the ureteral orifice or to the control cohort, who received five injections of 2 mL of 0.9% normal saline in identical locations. Pain scale questionnaires were provided to each subject preoperatively and at postoperative hours 2, 4, 8, 24, and 48 as well as on the day of stent removal. Student's t test and Wilcoxon signed rank sum tests were used for Gaussian and nonparametric data, respectively. RESULTS Twenty-two patients were randomized evenly into the two cohorts. The ropivacaine group consisted of 11 patients (eight men and three women) with a mean age of 56.2 years (standard deviation [SD] = 12, range 27-69), and the saline group consisted of eleven patients (six men and five women) with a mean age of 47.8 years (SD = 6.6, range 37-58). Intraoperative parameters appeared similar between the two cohorts. Intraoperative and postoperative narcotic usage was not different between the two groups, except at postoperative hour 2 when it favored the ropivacaine cohort (P = 0.05). Trends favoring ropivacaine in flank pain, bladder pain, genitalia pain, and hematuria domains were seen as long as 8 hours and up to the day of stent removal. Trends of less magnitude and duration were seen in the dysuria domain. No differences were seen in the frequency and urgency domains. CONCLUSIONS Our preliminary investigation with intravesical injection of ropivacaine before ureteroscopic surgery demonstrated trends toward decreased pain and voiding symptoms in this small-sample study. Inclusion of a larger sample should definitively address the effectiveness of intravesical ropivacaine and its impact on stent-related symptoms.