The feedback regulation of AGO mRNA by

The feedback regulation of AGO1 mRNA by miR168 is essential for normal plant development; the excess or deficiency of AGO1 protein caused by abiotic or biotic stress interferes with miRNA-guided gene expression, resulting in developmental defects, abnormal phenotypes or symptoms (Mallory et al., 2009). As discussed above, the AGO1 level is kept in check by miR168-directed AGO1 mRNA cleavage, translational inhibition, siRNA-mediated AGO1 mRNA degradation, and AGO1-mediated posttranscriptional stabilization of miR168 (Lanet et al., 2009; Mallory and Vaucheret, 2009; Várallyay et al., 2010; Vaucheret et al., 2006, 2004). Thus, the maintenance of AGO1 R 428 is essentially regulated by coordinated miR168- and siRNA-mediated pathways. Accordingly, we propose a model for the breakdown of AGO1 homeostasis in the G7-infected Rsv1 soybean (Fig. 8). G7 infection induces the over-expression of AGO1 mRNA that triggers the AGO1 siRNA-mediated silencing pathway for the enhanced AGO1 mRNA degradation. SGS3, RDR6, SDE5 and DCL4/2 are likely involved in this process (Fig. 8). On the other hand, G7 infection also induces the over-accumulation of miR168, which mediates cleavage or translational inhibition of AGO1 mRNA, leading to repression of the AGO1 protein (Fig. 8). Therefore, these two pathways together break down the equilibrium of AGO1 and down-regulate AGO1. However, since AGO1 may be negatively regulated by ZWILLE/PINHEAD/AGO10 (ZLL) activity (Brodersen et al., 2008), it remains unclear if the excess miR168 may target other AGO mRNAs such as AGO10 to break AGO homeostasis. G7 infection may also induce other miRNAs such as the miR2118/miR482 family to down-regulate the activity of the plant NB–LRR defense gene family through the production of phased tasiRNAs (Zhai et al., 2011). The precise mechanism by which AGO1 homeostasis in the Rsv1 soybean is broken by G7 infection through excess miR168-mediated cleavage of AGO1 mRNA and translational inhibition pathways remains to be further investigated.

Materials and methods

The authors are very grateful to Jamie McNeil (AAFC, Canada) for expert technical assistance and Alex Molnar (AAFC) for art work. The authors are indebted to Prof. John Hill (Iowa State University) for kindly providing the SMV G7 infectious clone and to Prof. Said Ghabrial (University of Kentucky) for the generous gift of the BPMV vector. This work was supported in part by AAFC Genomics R&D Initiative (GRDI), the Natural Sciences and Engineering Research Council of Canada (NSERC), and Grain Farmers Ontario (GFO).

Recent reports have demonstrated that “functional” cures for HIV infection might sometimes be possible (Saez-Cirion et al., 2013; Hutter et al., 2009). Cessation of antiretroviral therapy, with or without allogeneic bone marrow transplantation, however, often leads only to a delay in the rebound of viral loads (Henrich et al., 2013; Persaud et al., 2013). Even if some individuals can maintain control of their viral loads throughout their lifetime, the limitations of using these strategies globally are apparent. Development of a prophylactic vaccine is still an essential component of any strategy to eradicate HIV infection worldwide.
Recombinant rhesus cytomegalovirus (RhCMV) vaccine vectors expressing Gag, Pol, Env, and a Rev–Tat–Nef fusion protein have been shown to induce immunity that can control and eventually clear a pathogenic SIVmac239 challenge virus in roughly half of the vaccinated rhesus macaques (Hansen et al., 2011; Hansen et al., 2013). A variety of other vaccine vectors have also achieved varying levels of apparent sterilizing protection in multiple low dose challenges (Barouch et al., 2012; Patel et al., 2013; Flatz et al., 2012; Letvin et al., 2011). Multiple low-dose challenge models closely mimic a heterosexual exposure to HIV because of the transmission of a small number of founder viruses from the challenge stock (Keele et al., 2009; Li et al., 2010). In men who have sex with men (MSM), however, multiple founder viruses are often transmitted during the time of initial exposure (Li et al., 2010; Tully et al., 2012). Since a greater number of founder viruses are transmitted during a high-dose challenge, this model may more accurately predict the efficacy of vaccines to prevent the transmission of HIV in MSM.

The surplus of the National fund continues to increase every

The surplus of the National fund continues to increase every year. From the time of the creation of the National fund, the major revenue was non-tax (sales of property and agricultural lands), but every year the tax-revenue share is becoming a larger portion of the total revenue of the National fund (Fig. 4).
Davis et al. (2001) suggest measuring the effectiveness of the oil revenue fund by its effect on the relationship between the government expenditure and resource export earnings. The data shows a possible positive correlation between Kazakhstan\’s government expenditure and export of oil (Fig. 5). Also, the correlation looks stronger before 2001, while from 2001 on (after creation of the National fund), government expenditure looks less correlated with oil exports.
Nevertheless, there is a strong relationship between the government\’s revenue and expenditure with oil prices (Fig. 6).
An economy\’s dependency on oil resources can be measured in two ways (Liuksila, Garcia, & Bassett, 1994): external dependency shows how a country relies on oil exports to obtain foreign exchange (the share of oil export to total export), while fiscal dependency on the other hand, measures how the public sector relies on oil revenues (the share of oil taxes to total fiscal revenue). Data which is necessary to calculate external dependency of Kazakhstan is available, but oil revenue of Kazakhstan, which is needed to calculate fiscal dependency, is not available. That is why payments of oil and gas companies to the government of Kazakhstan from National Reports on the implementation of the extractive industry transparency initiative in Kazakhstan 2005–2011 (available at were used as approximate data. These reports provide payments of selected oil, gas and mining companies. During the R 428 2005–2008 payments by oil and gas companies are not separated from payments by mining companies. From 2009 only tax payments to the budget from the oil and gas companies (excluding mining companies) were used. Since in 2005 only payments of 38 oil, gas and mining companies available, while in 2006–2011 payments of 103–170 oil, gas and mining companies are available, we calculated fiscal dependency over the period 2006–2011. Oil revenue is divided between the government budget and the National fund. That is why total fiscal revenue was calculated as a sum of government revenue and payments of oil companies which were deposited into the National fund. Employing these measurements and plotting the share of Kazakhstan\’s oil exports to its total exports against the share of oil revenue to total revenue shows that Kazakhstan has a high external oil dependency (Fig. 7). About 70 percent of export earning and 40 percent of the fiscal revenue can be definitively associated with the economic activities of the oil sector. For comparison, Fig. 8, based on the work of Liuksila et al. (1994) shows that Nigeria, Saudi Arabia and Venezuela, which are also oil-dependent countries, have over 60 percent external and fiscal dependency (Fig. 8).
As is the case for most oil-producing countries, Kazakhstan has benefited from the upward trend in oil prices that is largely attributable to the strong demand for energy products over the past few years. A simple test of correlation depicted in the graph below affirms the positive correlation between Kazakhstan\’s GDP and the world oil price and between Kazakhstan\’s GDP and the country\’s oil production (Figs. 9 and 10).
The portion of fund\’s revenue in Kazakhstan\’s total revenue is constantly increasing (Fig. 11).

Theoretical analysis

Empirical work


In 1997, Zbigniew Brzezinski who once served as President Jimmy Carter\’s National Security Advisor published his seminal book The Grand Chessboard: American Primacy and Its Geostrategic Imperatives with the goal of formulating a long-term strategy for US foreign policy in the post-Cold War period. The central argument of the book was that the US primacy in the world depended foremost on its success in maintaining political, economic and military dominance over the Eurasian supercontinent, which Brzezinski presumptuously depicted as “the chief geopolitical prize for America”. Such a bold assertion, however, was actually based on the self-confidence of the US policymakers of the period who boasted a strong political standing and powerful economy at home and an unequalled political, economic, military and cultural influence abroad in the immediate aftermath of the Cold War.

br Statistical Analysis br Descriptive statistics are expressed as mean

Statistical Analysis

Descriptive statistics are expressed as mean ± standard deviation for continuous variables and as frequency and percentages for nominal variables. A paired t test was used to compare the excursion and peak motion speed between the right R 428 and the left diaphragm. The associations between the excursions of the diaphragms and participants\’ characteristics were evaluated by means of the Pearson\’s correlation coefficient and a simple linear regression or Student\’s t test depending on the type of variable (ie, continuous or nominal variable). Continuous variables were height, weight, BMI, tidal volume, vital capacity (VC, %VC), forced expiratory volume (FEV1, FEV1%, and %FEV1), and nominal variables were gender and smoking history. The robustness of the results of the univariate analyses was assessed with multiple linear regression models. The significance level for all tests was 5% (two sided). All data were analyzed using a commercially available software program (JMP; version 12, SAS, Cary, NC, USA).


Participants\’ Characteristics

Table 1 shows the clinical characteristics of all the participants (n = 172).

Excursions and Peak Motion Speeds of the Bilateral Diaphragm

Univariate Analysis of Associations Between the Diaphragmatic Excursions and Participants\’ Demographics

Figure 3. Estimated regression line of the excursion of the diaphragm on BMI or tidal volume. (a) Association between BMI and excursion of the right diaphragm. (b) Association between BMI and excursion of the left diaphragm. (c) Association between tidal volume and excursion of the right diaphragm. (d) Association between tidal volume and excursion of the left diaphragm. Lines show estimated regression (a–d). All scatterplots show correlations (P < 0.05). BMI, body mass index.Figure optionsDownload full-size imageDownload high-quality image (226 K)Download as PowerPoint slide

Multivariate Analysis of Associations Between the Excursions and Participants\’ Demographics

Multiple linear regression analysis using all variables as factors (Model 1) demonstrated Inversion weight, BMI, and tidal volume were independently associated with the bilateral excursion of the diaphragms (all P < 0.05) after adjusting for other clinical variables, including age, gender, smoking history, height, VC, %VC, FEV1, FEV1%, and %FEV1. There were no significant associations between the excursion of the diaphragms and variables including age, gender, smoking history, height, VC, %VC, FEV1, FEV1%, and %FEV1 (Table 4). Additionally, a multiple linear regression model using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2) was also fit as a sensitivity analysis, taking into account the correlation among variables (eg, BMI, height, and weight; VC and %VC; FEV1, FEV1%, and %FEV1). Model 2 (Supplementary Data S1) gave results consistent with Model 1 (Table 4): higher BMI and higher tidal volume were independently associated with the increased bilateral excursion of the diaphragms (all P < 0.05). The adjusted R2 in Model 1 was numerically higher than that in Model 2 (right, 0.19 vs. 0.16, respectively; left, 0.16 vs. 0.13, respectively).

br br The presence of better

The presence of better credit information quality available through credit registries/bureaus may reduce asymmetric information in the credit market. It lowers the likelihood for lenders to depend on credit rationing to mitigate information asymmetry across observationally distinguishable groups. Better depth of credit information may help lenders sort out profitable entrepreneurs or firms in sectors with high informal firm presence that would have been credit rationed in the absence of credit registries.

Overall, we contend that since a weak quality of institutional environment increases the costs and decreases the benefits assumed by formal firms and in addition, reduces the costs attributed to informality; we expect formal businesses competing against informal firms to be more credit-constrained than other formal SMEs.

3. Data, variables, descriptive statistics

(a). Data collection

Our main data source is the World Bank Enterprise Surveys (WBES) where we obtain firm-level information from 2009 to 2012 in 86 countries. We gather data regarding the institutional environment of each country from three sources—the Worldwide Governance Indicators developed by Kaufmann, Kraay, and Mastruzzi (2010), the Doing Business of the World Bank ( and the Credit Depth of Information index developed by the World Bank. We obtain the macroeconomic variables from the World Development Indicators.

We restrict our sample to micro, small, and medium firms because they R 428 are more likely to be affected by informal sector practices than large enterprises (González & Lamanna, 2007). Following the size definition used by the European Commission, we consider firms with less than 250 employees.4 Micro firms are defined as those employing less than 10 employees, small firms with at least 10 but no more than 50 employees, and medium firms with at least 50 but no more than 250 employees.

Table 1 (Appendix A) reports the percentage of firms facing competition from informal firms by country on the original survey sample (56.66%), on our study sample which consists of firms with information on all the variables defined in our paper (55.31%), and on our final sample consisting of our study sample but excluding large enterprises (56.3%). It shows that the proportion of firms facing competition from informal firms does not vary a lot across these three samples. Statistics on the final sample show that Dominica has the lowest percentage (10.71%) whereas Cameroon has the highest proportion (90.22%) of surveyed SMEs that have competitors from the informal sector. Table 2 (Appendix A) presents the distribution of firms according to their size on our study sample. Micro firms account for more than 24% of the study sample, while small firms and medium firms account for a little over 42% and 24%, respectively, and large firms with less than 9%. Thus, by restricting our sample to firms with less than 250 employees, we consider more than 91% of the study sample. Moreover, Table 2 also reports the percentage of firms facing competition from informal firms according to firm size. We observe that while 63.32% of the micro firms face competition from informal firms, on average, less than half of the large enterprises have competitors from the informal sector.

Measurements Blood samples were collected before and

2.3. Measurements
Blood samples were collected before and 4 weeks following R 428 with PPSV23, and serum samples were stored at −20 °C until used for testing. For serotype-specific IgG, antibody concentrations of 14 serotypes included in PPSV23 (serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) were measured using pneumococcal electrochemiluminescence (Pn ECL) assay [18]. Moreover, IgG concentration for serotype 6A, which is not included in PPSV23, was measured to assess possible cross-reactivity afforded by an immune response to serotype 6B, which is included in PPSV23. OPA was measured for 6 serotypes (3, 4, 6B, 14, 22F, and 23F) using multiplexed OPA (MOPA) assay [19]. The Pn ECL and OPA testing were performed at PPD Vaccines and Biologics Laboratory (Wayne, PA, USA) and at the University of Alabama (Birmingham, AL, USA), respectively.
Injection-site and systemic AEs occurring within 14 days postvaccination were collected. Deaths and other vaccine-related serious adverse events (SAEs) were recorded throughout the study. All subjects were asked to record any injection-site reaction and daily body temperature (oral method) in a vaccine diary for 5 consecutive days postvaccination. Causal relationship between the reported AEs and receipt of PPSV23 was assessed by the study investigators.

The cohort comprised patients who

The cohort comprised 50 patients who at the time of sampling were receiving two NRTIs plus either efavirenz (80%) or nevirapine and had a median duration of viral load suppression < 50 copies/ml of 6.4 years (Table 1). Patients with duration of suppressive ART above the median of 6.4 years were older and had a lower nadir CD4 cell count, a marginally higher current CD4 cell count, and lower frequencies of CD4 and CD8 R 428 expressing CD38 relative to subjects with shorter duration. They were also more likely to have experienced changes in the composition of the NRTI backbone after first starting ART. Overall 25/50 patients (50%) changed one or more component of the NRTI backbone, with median 1 drug change per subject (IQR 0–1). At the time of sampling, NRTI backbones were tenofovir/emtricitabine (37/50, 74%), abacavir/lamivudine (10/50, 20%), or zidovudine/lamivudine (3/50, 6%). Residual plasma HIV-1 RNA was detected in 29/50 patients (58%) at levels ranging between 1 and 35 copies/ml, whereas 2-LTR circular HIV-1 DNA was detected in 16/50 patients (32%) at levels ranging between 5 and 35 copies/106 PBMC. All subjects had detectable HIV-1 DNA, with total and integrated HIV-1 DNA levels of median 2.6 and 1.9 log10 copies/106 PBMC, respectively. None of the patients had detectable CMV DNA in plasma, whereas 3/50 patients (6%) had detectable EBV DNA.