Global Macroeconomic Performance: A Comparative Study Based on Composite Scores

This paper proposes a composite indicator designed to summarise in a single statistic a variety of different facets of macroeconomic performance and assesses relative performances of countries with respect to six macroeconomic variables, viz., the growth rate of real GDP, real per capita GDP, unemployment rate, fiscal balance, rate of inflation, and current account balance. An appropriate mathematical model to aggregate these variables to form composite scores has been implemented by adopting the MCDM (Multiple Criteria Decision Making) technique of TOPSIS (Technique for Order Preference by Similarity to Ideal Solution). This allows a parsimonious representation of a variety of different facets of macroeconomic performance and its inter-temporal comparison across countries. The distinctive features of the indicator relate to the domains covered, the normalisation methodology and the weights used for aggregation. Some existing indices like the Okun index and the Calmfors index turn out to be special cases of our proposed index. The data comprising a wide spectrum of countries and spanning the pre- and post- crisis years allow us to capture the effect of the recent global financial and economic crisis on the overall macroeconomic performance of countries relative to others. Not only do the relative performance scores show tremendous variability during the post-crisis years, but the measures of disarray are also at their highest, despite there being overall stability in the country rankings in terms of indicators, which are traditionally relied on, like GDP growth or per-capita GDP. A single graphical plot easily identifies countries that have performed consistently over time, and those whose overall macroeconomic performances have deteriorated sharply relative to others during the post-crisis years

Effects of Market Reforms and External Shocks on Indian Stock Indices: Evidence on Structural Breaks and Weak-Form Efficiency

This study explores stock market efficiency in India after allowing for potential structural changes induced by reforms processes and/or external shocks. The endogenous determination of structural break dates, using mostly Clemente, Montanes, & Reyes (1998) (CMR) methodology, allows us to identify important events in this respect. External shocks such as occasional stock market scams, policy and political regime changes, oil price shocks and the effect of global market meltdowns have caused abrupt or one time changes in the series mean (additive outlier model), while the reforms processes stand out to be the single most important cause for the gradual shifts in the level of stock indices (innovation outlier model). This underlines the importance of institution building and the domestic policy stance in countering external shocks

NEPHRO-PROTECTIVE ACTIVITY OF ISOLATED METHANOL FRACTIONS PHYTO-COMPOUND FROM BARK OF TERMINALIA ARJUNA

Objective: The aim of this study was to evaluate the antioxidant property of the isolated phytocompounds from TA (Terminalia arjuna) bark and in vivo study for nephro-protective and oxidative stress reducing activity in experimentally induced albino male rats.Methods: Fractions from methanol crude TA extract were collected by column chromatography and F27, F28, F29 fractions were selected on the basis of antioxidant property by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. The in vivo study performed by 30 albino male rats which were randomly divided into five groups: Group I (control)were taken normal food and water, Groups II (uremic) were injected acetaminophen intraperitoneally at the dose of 500 mg/kg/d for 10 d, Group III, IV and V(extract treatment) acetaminophen intraperitoneally at the dose of 500 mg/kg/d for 10 d with co-administered orally of methanol fraction F27, F28, F29 at the dose of 100 mg/kg/d for 15 d respectively.Results: After scarification of rats, the uremic marker plasma urea (80%), creatinine (85%) were elevated and antioxidant enzyme marker such as plasma SOD and catalase level were significantly increased (p<0.05)in Group IV compared to Group II. The total phenolic content of the F28 methanolic fraction was (815.48±8.11) mg gallic acid equivalent/g of extract. For isolation of available compound by 1H NMR study in F28 methanol fraction of TA bark was arjunoside IV which contained olefinic proton (a pair of carbon atom linked with double bond).Conclusion: Among the three methanolic fraction of TA bark, F28 was shown best antioxidative, nephron-protective and oxidative stress reducing property.Â

Tumor-Shed PGE2 Impairs IL2Rγc-Signaling to Inhibit CD4+ T Cell Survival: Regulation by Theaflavins

BACKGROUND:Many tumors are associated with decreased cellular immunity and elevated levels of prostaglandin E2 (PGE2), a known inhibitor of CD4+ T cell activation and inducer of type-2 cytokine bias. However, the role of this immunomodulator in the survival of T helper cells remained unclear. Since CD4+ T cells play critical roles in cell-mediated immunity, detail knowledge of the effect tumor-derived PGE2 might have on CD4+ T cell survival and the underlying mechanism may, therefore, help to overcome the overall immune deviation in cancer. METHODOLOGY/PRINCIPAL FINDINGS:By culturing purified human peripheral CD4+ T cells or Jurkat cells with spent media of theaflavin- or celecoxib-pre-treated MCF-7 cells, we show that tumor-shed PGE2 severely impairs interleukin 2 receptor gammac (IL2Rgammac)-mediated survival signaling in CD4+ T cells. Indeed, tumor-shed PGE2 down-regulates IL2Rgammac expression, reduces phosphorylation as well as activation of Janus kinase 3 (Jak-3)/signal transducer and activator of transcription 5 (Stat-5) and decreases Bcl-2/Bax ratio thereby leading to activation of intrinsic apoptotic pathway. Constitutively active Stat-5A (Stat-5A1 6) over-expression efficiently elevates Bcl-2 levels in CD4+ T cells and protects them from tumor-induced death while dominant-negative Stat-5A over-expression fails to do so, indicating the importance of Stat-5A-signaling in CD4+ T cell survival. Further support towards the involvement of PGE2 comes from the results that (a) purified synthetic PGE2 induces CD4+ T cell apoptosis, and (b) when knocked out by small interfering RNA, cyclooxygenase-2 (Cox-2)-defective tumor cells fail to initiate death. Interestingly, the entire phenomena could be reverted back by theaflavins that restore cytokine-dependent IL2Rgammac/Jak-3/Stat-5A signaling in CD4+ T cells thereby protecting them from tumor-shed PGE2-induced apoptosis. CONCLUSIONS/SIGNIFICANCE:These data strongly suggest that tumor-shed PGE2 is an important factor leading to CD4+ T cell apoptosis during cancer and raise the possibility that theaflavins may have the potential as an effective immunorestorer in cancer-bearer

Searching for Heavy-Tailed Probability Distributions for Modeling Real-World Complex Networks

Perhaps the most recent controversial topic in network science research is to determine whetherreal-world complex networks are scale-free or not. Recently, Broido and Clauset [A.D. Broido, A. Clauset,Nature Communication, 10, 1017 (2019)] asserted that the degree distributions of real-world networks arerarely power law under statistical tests. Such complex networks, including social, biological, information,temporal, and brain networks, are often heavy-tailed where the assumption on the scale-free nature of realworld heavy-tailed networks become insignificant as the complex system evolves over time. The failure ofpower law distribution in fitting the degree distribution data is mainly due to the presence of an identifiablenon-linearity within the entire degree distribution in a log-log scale of a complex heavy-tailed network. In thisstudy, we attempt to address this issue by proposing a new class of heavy-tailed probability distributions formodeling the entire degree distributions of complex networks. We introduce a new family of generalizedLomax models (GLM) to capture the non-linearity of these heavy-tailed networks. These newly introducedGLM-type distributions provide better fitting and greater flexibility to the entire node degree distributionof complex networks. Several statistical properties of the proposed model, such as extreme value andinferential statistical properties, are derived into this context. Interestingly, the GLM family belongs to thebasin of attraction of Frechet distribution, a heavy-tailed extreme value distribution. Rigorous experimentalanalysis showcases the excellent performance of the proposed family of distributions while fitting the heavytailed real-world complex networks over fifty real-world datasets in comparison with benchmark probabilitymodels. Our results show that GLM-type distributions are not rare, able to model almost 90% of the testednetworks accurately compared to benchmark probability models

Comparison of Lethal and Nonlethal Mouse Models of Orientia tsutsugamushi Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection

The antigenic diversity of Orientia tsutsugamushi as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of O. tsutsugamushi infection using the two strains, Karp (New Guinea) and Woods (Australia). The models included the lethal model: Karp intraperitoneal (IP) challenge; and the nonlethal models: Karp intradermal (ID), Woods IP, and Woods ID challenges. We monitored bacterial trafficking to the liver, lung, spleen, kidney, heart, and blood, and seroconversion during the 21-day challenge. Bacterial trafficking to all organs was observed in both the lethal and nonlethal models of infection, with significant increases in average bacterial loads observed in the livers and hearts of the lethal model. Multicolor flow cytometry was utilized to analyze the CD4+ and CD8+ T cell populations and their intracellular production of the cytokines IFNγ, TNF, and IL2 (single, double, and triple combinations) associated with both the lethal and nonlethal murine models of infection. The lethal model was defined by a cytokine signature of double- (IFNγ-IL2) and triple-producing (IL2-TNF-IFNγ) CD4+ T-cell populations; no multifunctional signature was identified in the CD8+ T-cell populations associated with the lethal model. In the nonlethal model, the cytokine signature was predominated by CD4+ and CD8+ T-cell populations associated with single (IL2) and/or double (IL2-TNF) populations of producers. The cytokine signatures associated with our lethal model will become depletion targets in future experiments; those signatures associated with our nonlethal model are hypothesized to be related to the protective nature of the nonlethal challenges

Scrub Typhus Vaccine Candidate Kp r56 Induces Humoral and Cellular Immune Responses in Cynomolgus Monkeys

A truncated recombinant 56-kDa outer membrane protein of the Karp strain of Orientia tsutsugamushi (Kp r56) was evaluated in cynomolgus monkeys (Macaca fascicularis) for immunogenicity and safety as a vaccine candidate for the prevention of scrub typhus. This recombinant antigen induced strong humoral and cellular immune responses in two monkeys and was found to be well tolerated. Antigen-specific immunoglobulin M (IgM) and IgG were produced to almost maximal levels within 1 week of a single immunization. Peripheral blood mononuclear cells from vaccinated animals showed an induction of antigen-specific proliferation and gamma interferon production. The Kp r56 was not as efficient as infection with live organisms in preventing reinfection but was able to reduce the inflammation produced at the site of challenge. This report describes the results of the first systematic study of the immunogenicity of a recombinant scrub typhus vaccine candidate in a nonhuman primate model

Re-confirmation of PGE₂ as the molecule behind tumor-induced perturbation in CD4⁺ T cell survival signaling.

<p>A, MCF-7 cells were treated with theaflavins or celecoxib or transfected with Cox-2-siRNA and the levels of Cox-2 and GAPDH (internal control) mRNA were determined by RT-PCR (<i>upper panel</i>). Western blot analysis was performed for the determination of levels of Cox-2 or α-Actin (internal control) proteins (<i>middle panel</i>). In parallel experiments the amount of tumor-secreted PGE₂ in the cell-free supernatant was determined by ELISA (<i>lower panel</i>). B, Purified CD4⁺ T cells were cultured in the presence of media alone or MCF-7-spent media (tumors were either pre-treated with 25 µg/ml theaflavins/3.5 ng/ml PGE₂/50 µM celecoxib or transfected with 300pmole Cox-2-siRNA) for 48 h. Expression levels of IL2Rγc and Bcl-2 as well as phosphorylation status of Jak-3/-Stat-5 were determined by Western blotting in which α-Actin was used as internal control (<i>upper panel</i>). In parallel experiments, flowcytometric determination of percent cell death (<i>lower panel</i>) was established. Values are mean±S.E.M. of three independent experiments.</p

Tumor-shed PGE₂ is responsible for CD4⁺ T cell apoptosis.

<p>A, Tumor-secreted PGE₂ over time in cell-free spent media of MCF-7 cells (control (○), Cox-2-siRNA-transfected (Δ) or theaflavin-treated (•) was determined by ELISA. B, Percent CD4⁺ T cell death (Annexin-V-PE⁺/7AAD⁺), induced by the spent media as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007382#pone-0007382-g002" target="_blank">Fig. 2A</a>, was plotted over time. Values are mean±S.E.M. of three independent sets of experiments.</p

Stat-5A transfection confers resistance to CD4⁺ T cells from tumor-induced death.

<p>A, Stat-5A (<i>left panel</i>) and Stat-5B (<i>right panel</i>) isoforms were immunoprecipitated from cell lysates using specific antibodies and then Western blotted with anti-phospho-tyrosine or anti-Stat-5A/Stat-5B antibodies to determine phosphorylation status of specific proteins. B, Jurkat T cells were transfected with control vector, wild-type <i>Stat-5A/Stat-5B</i>, C-terminal truncated <i>Stat-5A</i>₇₁₃/<i>Stat-5B</i>₇₁₈ or constitutively active <i>Stat-5A1*6</i> genes and were cultured in the presence of media alone or MCF-7 spent media (±theaflavins) for 48 h. Percent cell death (Annexin-V-PE⁺/7AAD⁺) was determined flow cytometrically. Values are mean±S.E.M. of three independent sets of experiments.</p