Miracle-dz/UniFAR-FTUs huggingface dataset:
Asc and Ipaf Inflammasomes Direct Distinct Pathways for Caspase-1 Activation in Response to Legionella pneumophila

ABSTRACT Caspase-1 activation is a key feature of the innate immune response of macrophages elicited by pathogens and a variety of toxins. Here, we determined the requirement for different adapter proteins involved in regulating host processes mediated by caspase-1 after macrophage infection by Legionella pneumophila. The adapter protein Asc was found to be important for caspase-1 activation during L. pneumophila infection. Activation of caspase-1 through Asc did not require the flagellin-sensing pathway involving the host nucleotide-binding domain and leucine-rich repeat-containing protein Ipaf (NLRC4). Asc-dependent caspase-1 activation was inhibited by high extracellular potassium levels, whereas Ipaf-dependent activation was unaffected by potassium treatment. Activation of caspase-1 in macrophages occurred independently of Nalp3 and proteasome activity, suggesting that a previously uncharacterized mechanism for caspase-1 activation through Asc may be triggered by L. pneumophila. Rapid pore formation and pyroptosis induced by L. pneumophila required caspase-1, Ipaf, and bacterial flagellin but occurred independently of Asc. Equivalent levels of active interleukin-18 (IL-18) were detected in the lungs of mice infected with a flagellin-deficient strain of L. pneumophila and Asc-deficient mice infected with wild-type L. pneumophila. Active IL-18 was undetectable in the lungs of Asc-deficient mice infected with an L. pneumophila flagellin mutant, indicating independent roles for Ipaf and Asc in caspase-1-mediated processing and release of IL-18 in vivo. Ipaf-dependent activation of caspase-1 restricted bacterial replication in vivo, whereas Asc was dispensable for restriction of L. pneumophila replication in mice. Thus, L. pneumophila-mediated caspase-1 activation involves the coordinate activities of inflammasomes differentially regulated by Ipaf and Asc.
Accumulation and Effects of Natural Mixtures of Persistent Organic Pollutants (POP) in Zebrafish after Two Generations of Exposure

Effects of exposure to environmentally realistic mixtures of persistent organic pollutants (POP) harvested from aquatic ecosystems in Norway were studied in an in vivo zebrafish model. POP were extracted from burbot (Lota lota) liver from two separate lakes, Lake Losna and Lake Mjøsa, and exposed to zebrafish through the diet in a two-generation study. Effects on survival, growth, sex ratio, and timing of puberty were investigated. In addition, the biomarkers 7-ethoxyresorufin O-deethylase (EROD) and vitellogenin (Vtg) were measured. The ratios of contaminant levels in extracts collected from Lake Mjøsa:Lake Losna were 6, 10, and 270 for polychlorinated biphenyls (PCB), dichlorodiphenyltrichloroethanes (DDT), and polybrominated diphenyl ethers (PBDE), respectively. The concentration range of POP measured in zebrafish was lower than in burbot originating from Lake Mjøsa, but comparable to concentrations previously reported in humans and wildlife. The results showed that exposure to environmentally realistic mixtures of POP exerted a negative effect on survival of fish in both generations. The marked drop in survival during 9–20 days post fertilization (dpf) suggested that this period may be a critical window for development. In both generations an earlier onset of puberty was observed and a higher proportion of males than females was noted in exposed fish compared to controls. Suprising effects of exposure were found on body weight. In the first generation (F0), body weight was significantly higher in both exposure groups compared to controls, while in the next generation (F1) the same exposures were associated with a decrease in body weight. Zebrafish exposed to relatively low quantities of POP showed a significant induction of biomarkers (EROD and Vtg), while fish exposed to higher exposure doses did not demonstrate induction.
Openness to Trade, Convergence in Tastes and Growth Rates Dierences in an Evolutionary Model of Structural Change

The paper develops a multi-sectorial growth model that links a Post-Keynesian macroframework to an evolutionary modelling of technical change and industrial dynamics. Economic growth is driven by the aggregate demand dynamics, function of domestic and foreign income dynamics and of the economies relative competitiveness. The latter results from the interactions between micro-dynamics of technical change and macro-dynamics as wage dynamics. The structures of the economies are directly linked to the structure of aggregate demand. Following Pasinetti (1981), Verspagen (1993) and Lorentz (2006), we assume that the structure of aggregate demand is derived from the combination of sectoral satiation level. We assume that these satiation levels are related to the characteristics of the goods proposed by the producers. Through this model we then aim to analyse the eect of this convergence in taste on the growth pattern of the economies.
Immigration and Perceived Ethnic Threat: Cultural Capital and Economic Explanations

This article aims to study to what extent the share of immigrants in a country influences individuals' perceptions of ethnic threat and how this can be explained by theories of economic and cultural threat. Following an economic logic, people with a weak socio-economic position should have a greater perception of ethnic threat. This would be more so if the share of low-educated immigrants in a country was relatively high. Following a cultural logic, greater perceptions of ethnic threat should be found among individuals with a weak cultural position, which would apply more strongly if the share of non-Western immigrants in a country was relatively high. Both theories are studied using data from the first round of the European Social Survey, enriched with country-specific variables. The results are discussed in terms of their implications for the theories under scrutiny and in the light of current scientific debates about the influence of immigration on Western societies.
Universal steganalysis using IQM and multiclass discriminator for digital images

As the modern world is gradually becoming internet and computer savvy with huge amount of information stored and exchanged over the internet through digital images for covert communication. There are different methods to hide information in digital images in different domain. First part of this paper gives concise information about different approaches for exiting steganalysis techniques for information detection in images. The objective of this paper is to know limitation of exiting Steganalysis techniques and proposed a Universal Steganalysis technique with the help of prominent statistical features of digital images through which the presence of information will be detected. There are lot of techniques for features extraction and classification. All techniques treat different images as same, therefore the different statistical properties of different images are considered for prominent feature selection. Second part consist of proposed model for universal Steganalysis.
Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C.

BACKGROUND & AIMS It is unclear whether hepatitis C virus (HCV) is eradicated in patients with chronic hepatitis C who achieved a sustained virologic response (SVR). METHODS In this long-term follow-up study, including chronic hepatitis C patients who achieved SVR after interferon-based therapy, the presence of residual HCV RNA in serum, liver, and peripheral blood mononuclear cells (PBMCs) was assessed, using transcription-mediated amplification (sensitivity, <9.6 IU/mL). The benefit of SVR on liver fibrosis was evaluated using the METAVIR score. RESULTS A total of 344 patients were followed up for a median duration of 3.27 years (range, 0.50-18 y; interquartile range [IQR], 1.68-5.35 y). A total of 114 patients had a posttreatment liver tissue (median, 0.50 y; range, 0-14 y; IQR, 0-3.5 y) and a total of 156 had one PBMC (median, 3.0 y; range, 0.50-18 y; IQR, 1.25-5.50 y). Serum HCV RNA remained undetectable (1300 samples), indicating that none of the patients had a relapse. HCV RNA was detectable in 2 of 114 (1.7%) liver specimens, and in none of 156 PBMC specimens. Histologic analysis of 126 paired pretreatment and posttreatment liver biopsy specimens (median, 0.50 y; range, 0-14 y; IQR, 0-3.5 y) showed that fibrosis stage was improved in 56%, stable in 32%, deteriorated in 12%. Regression of cirrhosis was observed in 9 of 14 (64%) (95% confidence interval, 39-89) patients. No cirrhosis decompensation was observed, and 3 patients developed hepatocellular carcinoma. CONCLUSIONS In this large cohort of chronic hepatitis C patients, SVR was durable up to 18 years after treatment cessation, in addition to fibrosis stability/improvement (88%) and cirrhosis regression (64%). The presence of residual HCV RNA was observed only in liver tissue (1.7%). This result strongly suggests that SVR may be considered to show eradication of HCV infection.
Strategyproof and Nonbossy Multiple Assignments

We consider the allocation of heterogeneous indivisible objects without using monetary transfers. Each agent may be assigned more than one object. We show that an allocation rule is strategyproof, nonbossy, and satisfies citizen sovereignty if and only if it is a sequential dictatorship. In a sequential dictatorship agents are assigned their favorite objects that are still available, according to a sequentially endogenously determined hierarchy of the agents. We also establish that replacing nonbossiness by a stronger criterion restricts the characterized class of allocation rules to serial dictatorships, in which the hierarchy of the agents is fixed a priori.
Replication Study of Ulcerative Colitis Risk Loci in a Lithuanian–Latvian Case–Control Sample

Background:Differences between populations might be reflected in their different genetic risk maps to complex diseases, for example, inflammatory bowel disease. We here investigated the role of known inflammatory bowel disease–associated single nucleotide polymorphisms (SNPs) in a subset of patients with ulcerative colitis (UC) from the Northeastern European countries Lithuania and Latvia and evaluated possible epistatic interactions between these genetic variants. Methods:We investigated 77 SNPs derived from 5 previously published genome-wide association studies for Crohn's disease and UC. Our study panel comprised 444 Lithuanian and Latvian patients with UC and 1154 healthy controls. Single marker case–control association and SNP-SNP epistasis analyses were performed. Results:We found 14 SNPs tagging 9 loci, including 21q21.1, NKX2-3, MST1, the HLA region, 1p36.13, IL10, JAK2, ORMDL3, and IL23R, to be associated with UC. Interestingly, the association of UC with previously identified variants in the HLA region was not the strongest association in our study (P = 4.34 × 10−3, odds ratio [OR] = 1.25), which is in contrast to all previously published studies. No association with any disease subphenotype was found. SNP-SNP interaction analysis showed significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes and increased risk for UC (P = 1.64 × 10−6, OR = 2.44). The association has been confirmed in the Danish study group (P = 0.04, OR = 3.25). Conclusions:We confirmed the association of the 9 loci (21q21.1, 1p36.13, NKX2-3, MST1, the HLA region, IL10, JAK2, ORMDL3, and IL23R) with UC in the Lithuanian–Latvian population. SNP-SNP interaction analyses showed that the combination of SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk for UC.
Lung Transplant Ischemia Reperfusion Injury: Metalloprotease Inhibition Down-regulates Exposure of Type V Collagen, Growth-Related Oncogene-Induced Neutrophil Chemotaxis, and Tumor Necrosis Factor-α Expression

Background. Immunity to type V collagen [col(V)] contributes to lung transplant rejection. Matrix metalloproteases (MMPs), which are induced by transplant-related ischemia-reperfusion injury (IRI), could expose col(V) and regulate local IRI-induced inflammation. Methods. To test the hypothesis that MMPs induce col(V) exposure and inflammation, Wistar-Kyoto rats were treated with the MMP inhibitor, COL-3, before inducing lung IRI without transplantation, and in parallel studies, Wistar-Kyoto lung donor and recipients were treated with COL-3 pre- and postisograft lung transplantation. Results. Ischemia-reperfusion injury induced growth-related oncogene/CINC-1-dependent neutrophil influx, and up-regulated tumor necrosis factor-α. MMP2 and MMP9, induced at 4 and 24 hr after IRI, respectively, were associated with detection of antigenic col(V) in bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-α; abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the donor before lung harvest and in the recipient after lung transplantation resulted in improved oxygenation and diminished polymorphonuclear leukocyte influx into the isograft. Conclusion. MMP inhibition may be a potential therapy to prevent release of antigenic col(V) and ameliorate IRI in the transplant recipient.
Animal Disease Economic Impacts: A Survey of Literature and Typology of Research Approaches

Animal diseases such as bovine spongiform encephalopathy (BSE) are a threat to the animal product marketing sector and the broader economy. Policy makers and industry stakeholders seek a means of assessing a disease threat's economic impacts when evaluating prevention and mitigation measures. But, differences in the focus of the impact analysis (production level, market prices, welfare), level of analysis (geographically, marketing phase) and proposed policy alternatives all influence the analytical approach. This paper surveys previous research, focusing on methodological approaches and results. Drawing from past research and future economic data needs, a typology is developed to guide researchers when defining the scope and policy alternatives of various research approaches.
The Effect of Selection for Sternopleural Bristle Number on Mating Behaviour in DROSOPHILA MELANOGASTER.

I N a separate paper we have reported the results of disruptive selection for sternopleural bristle number in Drosophila melanogaster. Experimental procedures were the same as those of THODAY and GIBSON (1 962) and THODAY ( 1964), but in contrast to their results, disruptive selection did not lead to reproductive isolation between the high and low parts of the population. One explanation for THODAY and GIBSON’S results would be the existence in their population of a genetic correlation between bristle number and isolation tendency, which may even have been expressed in the unselected population as assortative mating for bristle number. If this were so, lines directly selected for high and for low bristle number would show isolation. as our
Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology

Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions.
The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner

Tumors with mutant BRAF and some with mutant RAS are dependent upon ERK signaling for proliferation, and their growth is suppressed by MAPK/ERK kinase (MEK) inhibitors. In contrast, tumor cells with human EGF receptor (HER) kinase activation proliferate in a MEK-independent manner. These findings have led to the development of RAF and MEK inhibitors as anticancer agents. Like MEK inhibitors, the RAF inhibitor PLX4032 inhibits the proliferation of BRAFV600E tumor cells but not that of HER kinase-dependent tumors. However, tumors with RAS mutation that are sensitive to MEK inhibition are insensitive to PLX4032. MEK inhibitors inhibit ERK phosphorylation in all normal and tumor cells, whereas PLX4032 inhibits ERK signaling only in tumor cells expressing BRAFV600E. In contrast, the drug activates MEK and ERK phosphorylation in cells with wild-type BRAF. In BRAFV600E tumor cells, MEK and RAF inhibitors affect the expression of a common set of genes. PLX4032 inhibits ERK signaling output in mutant BRAF cells, whereas it transiently activates the expression of these genes in tumor cells with wild-type RAF. Thus, PLX4032 inhibits ERK signaling output in a mutant BRAF-selective manner. These data explain why the drug selectively inhibits the growth of mutant BRAF tumors and suggest that it will not cause toxicity resulting from the inhibition of ERK signaling in normal cells. This selectivity may lead to a broader therapeutic index and help explain the greater antitumor activity observed with this drug than with MEK inhibitors.
SGR1, SGR2, and SGR3: Novel Genetic Loci Involved in Shoot Gravitropism in Arabidopsis thaliana

In higher plants shoots show a negative gravitropic response but little is known about its mechanism. To elucidate this phenomenon, we have isolated a number of mutants with abnormal shoot gravitropic responses in Arabidopsis thaliana. Here we describe mainly three mutants: sgr1–1, sgr2–1, and sgr3–1 (shoot gravitropism). Genetic analysis confirmed that these mutations were recessive and occurred at three independent loci, named SGR1, SGR2, and SGR3, respectively. In wild type, both inflorescence stems and hypocotyls show negative gravitropic responses. The sgr1–1 mutants showed no response to gravity either by inflorescence stems or by hypocotyls. The sgr2–1 mutants also showed no gravitropic response in inflorescence stems but showed a reduced gravitropic response in hypocotyls. In contrast, the sgr3–1 mutant was found to have reduced gravitropic responses in inflorescence stems but normal gravitropic responses in hypocotyls. These results suggest that some genetic components of the regulatory mechanisms for gravitropic responses are common between inflorescence stems and hypocotyls, but others are not. In addition, these sgr mutants were normal with respect to root gravitropism, and their inflorescence stems and hypocotyls could carry out phototropism. We conclude that SGR1, SGR2, and SGR3 are novel genetic loci specifically involved in the regulatory mechanisms of shoot gravitropism in A. thaliana.
A biphasic calcium phosphate coating for potential drug delivery affects early osseointegration of titanium implants

BACKGROUND Calcium phosphate (CaP) surface coatings may accelerate osseointegration and serve as a drug delivery system for mineral-binding biomolecules. In a pilot study, the impact of a commercially available, thin CaP coating on early osseous bone remodeling was compared with a modern, subtractive-treated rough surface (SLA-like) in an animal trial. METHODS In 16 rabbits, 32 endosseous implants (CaP; n = 16, SLA-like; n = 16) were bilaterally inserted in the proximal tibia after randomization. After 2 and 4 weeks, bone-implant contact (BIC;%) in the cortical (cBIC) and the trabecular bone (sBIC) as well as volume of bone within the screw thread with the highest amount of new-formed bone (area;%) were analyzed. RESULTS After 2 weeks, cBIC was significantly higher for CaP when compared with SLA-like (58 ± 7% versus 40.4 ± 18%; P = 0.021). sBIC for CaP was 14.7 ± 8% and for SLA-like 7.2 ± 7.8% (P = 0.081). For area, the mean volumes were 82.8 ± 10.8% for CaP and 73.6 ± 22% for SLA-like (P = 0.311). After 4 weeks, cBIC was 42.9 ± 13% for the CaP and 46.5 ± 29.1% for the SLA-like group (P = 0.775). An sBIC of 6.9 ± 9.3% was calculated for CaP and of 12.3 ± 4.8% for SLA-like (P = 0.202). The values for area were 62.3 ± 24.1% for CaP and 50.1 ± 25.9% for SLA-like (P = 0.379). CONCLUSIONS The CaP coating has putative additional advantages in the early osseoconduction phases. It seems suitable for a feasible and clinical applicable bioactivation.
Let There Be Light—Optoprobes for Neural Implants

Over the past decades, optical technologies have entered neural implant technologies. Applications such as optogenetics, near-infrared spectroscopy (NIRS), and direct-near-infrared stimulation (NIS) request technical devices that combine electrical and optical recording as well as stimulation capabilities using light sources and/or optical sensors. Optoprobes are the technical devices that meet these requirements. This paper provides basic insights into optogenetic mechanisms, the background of NIRS and NIS, and focuses on fundamental requirements of technical systems from a biological background. The state of the art of optoprobes is reviewed and attention is drawn on the potential long-term stability of these technical devices for chronic neural implants. Further, material selection for stiff and flexible devices, applicable light sources, waveguide and coupling concepts, packaging paradigms as well as system assembly and integration aspects are discussed in view of biocompatible and biostable devices. This paper also considers the physical background of light scattering and heat generation when light sources are implanted into biological tissue.
Consolidating Corporate Control: Divisional Versus Whole-Company Leveraged Buyouts

We examine the empirical relation between firm characteristics and the likelihood of choosing a restructuring choice between two types of leveraged buyouts: a whole-company leveraged buyout (WLBO) and a divisional leveraged buyout (DLBO). Our findings suggest that firm characteristics such as volatility of cash flow and growth potential play an important role in determining a firm's restructuring choice between a WLBO and a DLBO. In particular, firms with greater volatility of cash flow and/or greater future growth potential are more likely to adopt a DLBO than a WLBO as their restructuring choice. These results are consistent with the notion that although low-growth, high-cash-flow firms would create the most value for stockholders by paying out cash and tying future cash flows to the firm's debt service through a WLBO, high-growth, low-cash-flow firms would be better off by selling assets if those assets would be better managed under a DLBO. Southern Finance Association and the Southwestern Finance Association.
On the pricing of undesirable state-contingent outputs

This paper adapts the models of Frisch (1965) and Murty and Russell (2006) on the modelling of undesirable outputs to a state-contingent setting with a specific emphasis on agricultural production technologies. The Chambers and Fare (2008) approach to calculating shadow prices for DEA technologies is extended to encompass state-contingent production problems. These contributions are implemented empirically using a dataset obtained from a survey of Catalan farmers.