Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial

Introduction Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents. Methods In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs. Results Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly. Conclusions The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population. Trial registration ClinicalTrials.gov NCT02178748
Essays on Credit Ratings

This thesis consists of four self-contained articles, all of which contribute to the empirical research on credit ratings. Broadly speaking, the first two papers highlight two less ordinary “uses” of credit ratings, in the context of (1) measuring financial constraints and (2) bond market segmentation. The last two papers focus on a relatively new concept in the credit ratings’ literature, specifically the time variation in rating standards, by looking at the sovereign credit ratings, and at how the time variation in rating standards has been measured and interpreted in prior literature.By using an extensive set of tests and corporate investment decisions indicating various degrees of financial constraints, the first paper provides first-hand evidence of the ability of credit ratings to capture corporate responses consistent with various levels of financial constraints. We find that they outperform six common financial constraints proxies in each of our tests and shocks.In the second paper, I use an exogenous change in the index inclusion criteria for a large, widely followed bond index, to show that bonds also exhibit an “index” effect following either addition or deletion to the bond index. Furthermore, this exogenous change leads to different types of index effects, allowing me to compare, for the first time, the relative effect of positive (addition) and negative (deletion) changes in a bond index composition. In this comparison, I find that index addition triggers a market reaction twice as large as index deletion, suggesting that investor awareness may be an important channel for bond pricing.The third paper is the first to provide evidence of rating conservatism for sovereign (i.e. country) credit ratings. I find that a sovereign that received an AA rating in 1993 would only get an A+ twenty years later in spite of maintaining the same economic environment, and this change in conservatism is not justified by an increase in the default rates or by a riskier global environment.In the final paper, I revisit the method commonly used for measuring time variation (i.e. conservatism) of rating standards over time, and I find that the decrease in the year coefficients (i.e. the measure for conservatism according to prior research) is largely a result of common secular trends in the financial variables included in the model. While my findings do not disprove the existence of conservatism, they suggest that its true magnitude may be significantly lower, and that other empirical methods might be more suitable for its assessment. (Less)
Intravenous mycophenolate mofetil with low-dose oral tacrolimus and steroid induction for live donor liver transplantation.

OBJECTIVES Mycophenolate mofetil (MMF) is used in liver transplantation (LTx) to reduce rejection, nephrotoxicity, neurotoxicity, and the need for steroids. Lower trough concentrations and bioavailability have been reported with oral MMF in first week after LTx. These parameters improve after the first month postoperatively. Previously published studies have used oral formulations of MMF. In this study, we sought to examine survival, rejection, and nephrotoxicity rates using IV MMF in live donor liver transplantation (LDLT). PATIENTS AND METHODS Twenty-eight patients (mean age, 50.1 years; 15 men, 13 women) were examined between January 2000 and January 2004 with a mean follow-up of 17 months for survival, rejection, and renal function. RESULTS Four patients died at 2, 5, 8, and 18 months after LDLT from sepsis (n = 3) and recurrent hepatocellular carcinoma (n = 1). There were no retransplants; hence, patient and graft survival rates were the same (82.4%). Three patients (10.7%) experienced acute cellular rejection requiring treatment. The mean serum creatinine level prior to LDLT was 0.9 +/- 0.4 mg/dL, which remained stable throughout the study. One patient required hemodialysis during the perioperative period for 8 days. CONCLUSIONS In the current study, we demonstrate a new strategy of IV MMF administration with low-dose tacrolimus that provides for lower rates of acute rejection, better preservation of renal function, and one that is better tolerated compared with historical treatments after LTx.
Utilization of Homotypic and Heterotypic Proteins of Vesicular Stomatitis Virus by Defective Interfering Particle Genomes for RNA Replication and Virion Assembly: Implications for the Mechanism of Homologous Viral Interference

ABSTRACT Defective interfering (DI) particles of Indiana serotype of vesicular stomatitis virus (VSVInd) are capable of interfering with the replication of both homotypic VSVInd and heterotypic New Jersey serotype (VSVNJ) standard virus. In contrast, DI particles from VSVNJ do not interfere with the replication of VSVInd standard virus but do interfere with VSVNJ replication. The differences in the interfering activities of VSVInd DI particles and VSVNJ DI particles against heterotypic standard virus were investigated. We examined the utilization of homotypic and heterotypic VSV proteins by DI particle genomic RNAs for replication and maturation into infectious DI particles. Here we show that the RNA-nucleocapsid protein (N) complex of one serotype does not utilize the polymerase complex (P and L) of the other serotype for RNA synthesis, while DI particle genomic RNAs of both serotypes can utilize the N, P, and L proteins of either serotype without serotypic restriction but with differing efficiencies as long as all three proteins are derived from the same serotype. The genomic RNAs of VSVInd DI particles assembled and matured into DI particles by using either homotypic or heterotypic viral proteins. In contrast, VSVNJ DI particles could assemble only with homotypic VSVNJ viral proteins, although the genomic RNAs of VSVNJ DI particles could be replicated by using heterotypic VSVInd N, P, and L proteins. Thus, we concluded that both efficient RNA replication and assembly of DI particles are required for the heterotypic interference by VSV DI particles.
Oxidation of Cu,Zn-superoxide Dismutase by the Myeloperoxidase/Hydrogen Peroxide/Chloride System: Functional and Structural Effects

This study investigated the functional and structural effects of bovine Cu,Zn-superoxide dismutase (Cu,Zn-SOD) oxidation by the myeloperoxidase (MPO)/hydrogen peroxide (H 2 O 2 )/chloride system and reagent hypochlorous acid (HOCl). Exposure to HOCl led to a fast inactivation accompanied by structural alterations. The residual SOD activity depended on the reactants concentration ratio and on the exposure time. The concomitant high consumption of HOCl indicated the presence of multiple targets on the protein. As assessed by SDS/PAGE, HOCl caused the dissociation of the protein into protomers at 16 kDa stable to both SDS and reducing conditions. Results from isoelectric focusing gels showed that exposure to HOCl induced the formation of modified protein derivatives, with a more acidic net electric charge than the parent molecule, consistent with the presence of additional ions observed in the electrospray ionization mass spectra. The reaction of protein with HOCl resulted in changes in protein conformation as assessed by the UV fluorescence and oxidation of the unique methionine and tyrosine, chlorination of several lysines with formation of chloramines. There was no significant formation of dityrosine and carbonyl groups. Exposure to high levels of HOCl resulted in complete enzyme inactivation, loss of additional lysine, histidine and arginine residues and coincident detection of weakly bound zinc and copper using 4-pyridylazaresorcinol. Collectively, the results suggest that the decrease of the dismutase activity is probably related to both dissociation into protomers and unfolding due to extensive oxidative modifications of amino acids.
Intragenomic Heterogeneity of Internal Transcribed Spacer rDNA in Neotropical Malaria Vector Anopheles aquasalis (Diptera: Culicidae)

Abstract Intragenomic heterogeneity of the internal transcribed spacer (ITS) array was investigated in Anopheles aquasalis Curry mosquitoes from two geographic locations in each of Brazil and Venezuela, and one in Suriname. Polymerase chain reaction-amplified copies of the ITS were cloned and sequenced. The length of the entire array ranged from 782 to 990 bp, with most variation due to microsatellite insertions in ITS1. We detected 40 different ITS1 sequences and 15 different ITS2 sequences of the 71 to 72 clones examined. The sequence divergence within localities ranged from 0.002 to 0.043 for ITS1 and from 0 to 0.006 for ITS2. Point mutations were common to both spacer regions, but dinucleotide microsatellite repeats were restricted to ITS1. Sequences from neither ITS1 nor ITS2 had a diagnostic distribution or were informative in distinguishing these populations, providing additional support for the status of An. aquasalis as a single species.
Transparency, Credibility and Predictability of Monetary Policy under Inflation Targeting in South Africa.

The adoption of inflation targeting in 2000 aimed to enhance the transparency and effectiveness of monetary policy in South Africa. Quantitative indexes reveal a strong rise in the transparency of monetary policy between 1994 and 2007. Inflation and interest rate expectations data, forward interest rate data and estimates of an interest rate policy rule, are used to explore the credibility and predictability of monetary policy since adopting inflation targeting. The evidence points to the new monetary policy framework being well-entrenched in financial markets’ expectations as early as 2001. Only small declines in interest rate forecast errors arise thereafter.
Global Political Risk and International Stock Returns

Using novel measures of politics-policy uncertainty we document predictable variation in stock market returns across countries. Country characteristics and existing global and local risk factors do not account for such predictability, leading to large abnormal returns, up to 15% per annum. We identify a global political risk factor (P-factor) commanding a risk premium of 11% per annum. Countries with high politics-policy uncertainty covary positively with the P-factor, thus earning higher average returns. Augmenting the global market portfolio with the P-factor significantly reduces pricing errors and improves cross-sectional fit. Politics-policy uncertainty affects returns through both cash flow and discount rate channels.
Changing patterns of Hodgkin lymphoma incidence in Singapore

A bimodal age‐specific incidence pattern with a relatively high proportion of cases occurring in adolescents and young adults is a hallmark of Hodgkin lymphoma (HL) epidemiology in Western industrialized countries. The young adult incidence peak is believed to reflect the association between HL risk in young adults and an affluent childhood socioeconomic environment. However, the dynamic development of the young adult incidence peak following socioeconomic development implied by this interpretation has scarcely been demonstrated in a single population over time. We, therefore, analyzed incidence patterns of HL in Singapore between 1968 and 2004, during which time period a socioeconomic transition towards Western World lifestyles took place. As hypothesized a HL incidence peak emerged among adolescents and young adults in Singapore. Thus, in the age groups 15–19 and 20–24 years incidence rates increased annually by 7.0% (95% confidence interval 3.4%–10.7%) and 3.4% (0.1%–6.8%), respectively, in men and by 13.7% (9.1%–18.6%) and 12.2% (7.8–16.8%), respectively, in women between 1968 and 2004. However, the incidence peak remained considerably lower than what can be observed in young adults in the Western World. It remains to be determined to what extent the current lower incidence of HL in young Asian adults should be attributed to birth cohort phenomena, as would be suggested by continued increase in incidence, and to ethnic variation in HL susceptibility between Asian and non‐Asian populations, respectively. © 2008 Wiley‐Liss, Inc.
Comparison of the anesthetic effects of intrathecal levobupivacaine + fentanyl and bupivacaine + fentanyl during caesarean section.

BACKGROUND Regional anesthesia techniques are increasingly preferred for caesarean section. The aim of the present study was to compare the anesthetic effects of levobupivacaine + fentanyl and bupivacaine + fentanyl on the mother and newborn during elective caesarean section under spinal anesthesia. METHODS In this prospective study, 50 gravidas, who were scheduled for cesarean section were enrolled after Ethics Committee approval had been obtained. The patients were randomized into one of the following two groups: bupivacaine + fentanyl group (group B; n = 25), 7.5 mg of 0.5% bupivacaine + 15 microg fentanyl intrathecally; levobupivacaine + fentanyl group (group L; n = 25), 7.5 mg of 0.5% levobupivacaine + 15 microg fentanyl intrathecally. The patients were immediately placed in supine position with 20-30 degrees head up-tilt. The level of sensory and motor blocks were evaluated by pin-prick test and Bromage scale, respectively. RESULTS The time to sensory block at the T4 dermatome was shorter in group B (group B, 4.8 min; group L, 6.0 min; p < 0.05). The time to maximum motor block was also shorter in group B (group B, 3.4 min; group L, 4.7 min; p < 0.05). The duration of analgesia was longer in group L compared to group B (group B, 102 min; group L, 118 min; p < 0.05). CONCLUSIONS Time to sensory and maximum motor block was shorter in the bupivacaine + fentanyl group. On the other hand, a longer duration of analgesia was achieved in the levobupivacaine + fentanyl group. Although levobupivacaine is a novel drug, it is a good alternative for bupivacaine.
Performance Measurement in Emerging Market Social Enterprises using a Balanced Scorecard

Abstract Performance measurement in social enterprises is important; however, up to now, there is no agreement on which tool to use, especially for those in emerging markets. Therefore, this study used a balanced scorecard to quantitatively measure performance of 446 social enterprises in South Africa. The findings show that the adapted perspectives of a balanced scorecard such as customer, organizational learning and growth, finance and internal processes can be used as performance indicators. This study developed and tested an adapted balanced scorecard that can be used as a performance instrument for enterprises that do not have specific measurement tools.
Effect of concentration on the accuracy of convective imaging distribution of a gadolinium-based surrogate tracer.

OBJECT Accurate real-time imaging of coinfused surrogate tracers can be used to determine the convective distribution of therapeutic agents. To assess the effect that a concentration of a Gd-based surrogate tracer has on the accuracy of determining the convective distribution, the authors infused different concentrations of Gd-diethylenetriamine pentaacetic acid (DTPA) in primates during MR imaging. METHODS Five nonhuman primates underwent convective infusion (1 or 5 mM, 21-65 μl) of Gd-DTPA alone, Gd-DTPA and (14)C-sucrose, or Gd-DTPA and (14)C-dextran into the bilateral striata. Animals underwent real-time MR imaging during infusion (5 animals) and autoradiographic analysis (2 animals). RESULTS Gadolinium-DTPA could be seen filling the striata at either concentration (1 or 5 mM) on real-time MR imaging. While the volume of distribution (Vd) increased linearly with the volume of infusion (Vi) for both concentrations of tracer (1 mM: R(2) = 0.83; 5 mM: R(2) = 0.96), the Vd/Vi ratio was significantly (p < 0.0001) less for the 1-mM (2.3 ± 1.0) as compared with the 5-mM (7.4 ± 1.9) concentration. Autoradiographic and MR volumetric analysis revealed that the 5-mM concentration most accurately estimated the Vd for both small (sucrose [359 D], 12% difference between imaging and autoradiographic distribution) and large (dextran [70 kD], 0.2% difference) molecules compared with the 1-mM concentration (sucrose, 65% difference; dextran, 68% difference). CONCLUSIONS The concentration of infused Gd-DTPA plays a critical role in accurately assessing the distribution of molecules delivered by CED. A 5-mM concentration of Gd-DTPA most accurately estimated the Vd over a wide range of molecular sizes.
A brittle star-like robot capable of immediately adapting to unexpected physical damage

A major challenge in robotic design is enabling robots to immediately adapt to unexpected physical damage. However, conventional robots require considerable time (more than several tens of seconds) for adaptation because the process entails high computational costs. To overcome this problem, we focus on a brittle star—a primitive creature with expendable body parts. Brittle stars, most of which have five flexible arms, occasionally lose some of them and promptly coordinate the remaining arms to escape from predators. We adopted a synthetic approach to elucidate the essential mechanism underlying this resilient locomotion. Specifically, based on behavioural experiments involving brittle stars whose arms were amputated in various ways, we inferred the decentralized control mechanism that self-coordinates the arm motions by constructing a simple mathematical model. We implemented this mechanism in a brittle star-like robot and demonstrated that it adapts to unexpected physical damage within a few seconds by automatically coordinating its undamaged arms similar to brittle stars. Through the above-mentioned process, we found that physical interaction between arms plays an essential role for the resilient inter-arm coordination of brittle stars. This finding will help develop resilient robots that can work in inhospitable environments. Further, it provides insights into the essential mechanism of resilient coordinated motions characteristic of animal locomotion.
Suppression of villin expression by antisense RNA impairs brush border assembly in polarized epithelial intestinal cells.

We have used an antisense RNA strategy to investigate the role of the actin‐associated protein, villin, in the brush‐border morphogenesis of human intestinal CaCO2 cells. Stable expression of a cDNA encoding antisense villin RNA resulted in the permanent down‐regulation of the endogenous villin message and dramatically affected brush‐border assembly. Ultrastructural and immunolocalization studies revealed that epithelial cell polarity was largely maintained. However, in contrast to brush‐border markers such as dipeptidyl‐peptidase IV, the apical localization of sucrase‐isomaltase was specifically impaired. Retransfection of the villin antisense‐expressing cell line with a cDNA encoding a partial sense villin RNA restored both brush‐border assembly and sucrase‐isomaltase apical expression. The suggestion that brush‐border morphogenesis may be important for the trafficking of certain proteins is discussed.
GASTROINTESTINAL HELMINTHS IN RACCOONS IN TEXAS

Raccoons (n=590) were collected from October 1999 to August 2003 from 35 counties across Texas, and gastrointestinal tracts were examined for helminth parasites. Prevalence was calculated and differences in mean abundance were examined among habitat ecoregions, age classes, and between sexes. Twenty different species of helminths (13 nematodes, two cestodes, two acanthocephalans, and three trematodes) were positively identified in the gastrointestinal tracts of 590 raccoons in Texas. Five of the 20 helminth species collected (Physaloptera rara, Placoconus lotoris, Molineus barbatus, Atriotaenia procyonis, and Macracanthorhynchus ingens) had a prevalence >20%. The total number of individuals of these five species (n=22,777) accounted for over 86% of the total number of individuals of all helminth species (n=26,426) collected. Subsequent analyses were based on these five helminths. Mean abundance differed among habitat ecoregions, age classes, and between sexes for all five parasites evaluated. This study is the most comprehensive statewide survey ever done of gastrointestinal helminths of raccoons across Texas. The five most prevalent helminths identified have all been reported in at least one previous survey, indicating that these parasites are not new to Texas and that raccoons are not naïve to the effects these parasites have on them. It may be helpful to wildlife rehabilitators, trappers, wildlife biologists, and other professionals to be aware of parasite abundance in raccoons from different areas of the state, as frequent human–raccoon interactions occur, and some of these parasites could be harmful to humans and domestic animals.
Increased Biofilm Formation by Nontypeable Haemophilus influenzae Isolates from Patients with Invasive Disease or Otitis Media versus Strains Recovered from Cases of Respiratory Infections

ABSTRACT Biofilm formation by nontypeable (NT) Haemophilus influenzae remains a controversial topic. Nevertheless, biofilm-like structures have been observed in the middle-ear mucosa of experimental chinchilla models of otitis media (OM). To date, there have been no studies of biofilm formation in large collections of clinical isolates. This study aimed to investigate the initial adhesion to a solid surface and biofilm formation by NT H. influenzae by comparing isolates from healthy carriers, those with noninvasive respiratory disease, and those with invasive respiratory disease. We used 352 isolates from patients with nonbacteremic community-acquired pneumonia (NB-CAP), chronic obstructive pulmonary disease (COPD), OM, and invasive disease and a group of healthy colonized children. We then determined the speed of initial adhesion to a solid surface by the BioFilm ring test and quantified biofilm formation by crystal violet staining. Isolates from different clinical sources displayed high levels of biofilm formation on a static solid support after growth for 24 h. We observed clear differences in initial attachment and biofilm formation depending on the pathology associated with NT H. influenzae isolation, with significantly increased biofilm formation for NT H. influenzae isolates collected from patients with invasive disease and OM compared with NT H. influenzae isolates from patients with NB-CAP or COPD and healthy colonized subjects. In all cases, biofilm structures were detached by proteinase K treatment, suggesting an important role for proteins in the initial adhesion and static biofilm formation measured by crystal violet staining.