Protection of Rhesus Monkeys by a DNA Prime/Poxvirus Boost Malaria Vaccine Depends on Optimal DNA Priming and Inclusion of Blood Stage Antigens

(Pk) malaria. This is a multi-stage vaccine that includes two pre-erythrocytic antigens, PkCSP and PkSSP2(TRAP), and two erythrocytic antigens, PkAMA-1 and PkMSP-1(42kD). The present study reports three further experiments where we investigate the effects of DNA dose, timing, and formulation. We also compare vaccines utilizing only the pre-erythrocytic antigens with the four antigen vaccine.In three experiments, rhesus monkeys were immunized with malaria vaccines using DNA plasmid injections followed by boosting with poxvirus vaccine. A variety of parameters were tested, including formulation of DNA on poly-lactic co-glycolide (PLG) particles, varying the number of DNA injections and the amount of DNA, varying the interval between the last DNA injection to the poxvirus boost from 7 to 21 weeks, and using vaccines with from one to four malaria antigens. Monkeys were challenged with Pk sporozoites given iv 2 to 4 weeks after the poxvirus injection, and parasitemia was measured by daily Giemsa stained blood films. Immune responses in venous blood samples taken after each vaccine injection were measured by ELIspot production of interferon-γ, and by ELISA.1) the number of DNA injections, the formulation of the DNA plasmids, and the interval between the last DNA injection and the poxvirus injection are critical to vaccine efficacy. However, the total dose used for DNA priming is not as important; 2) the blood stage antigens PkAMA-1 and PkMSP-1 were able to protect against high parasitemias as part of a genetic vaccine where antigen folding is not well defined; 3) immunization with PkSSP2 DNA inhibited immune responses to PkCSP DNA even when vaccinations were given into separate legs; and 4) in a counter-intuitive result, higher interferon-γ ELIspot responses to the PkCSP antigen correlated with earlier appearance of parasites in the blood, despite the fact that PkCSP vaccines had a protective effect

The Origin of Subdwarf B Star (I): the Formation Channels

Subdwarf B (sdB) stars (and related sdO/sdOB stars) are believed to be helium core-burning objects with very thin hydrogen-rich envelopes. In recent years it has become increasingly clear from observational surveys that a large fraction of these objects are members of binary systems. To better understand their formation, we here present the results of a detailed investigation of the three main binary evolution channels that can lead to the formation of sdB stars: the common envelope (CE) ejection channel, the stable Roche lobe overflow (RLOF) channel and the double helium white dwarfs (WDs) merger channel. We obtained the conditions for the formation of sdB stars from each of these channels using detailed stellar and binary evolution calculations where we modelled the detailed evolution of sdB stars and carried out simplified binary population synthesis simulations. The observed period distribution of sdB stars in compact binaries strongly constrains the CE ejection parameters. We also present the distribution of sdB stars in the $T_{\rm eff}$ - $\log g$ diagram, the Hertzsprung-Russell diagram and the distribution of mass functions.Comment: 20 pages, 23 figures, accepted for publication in MNRA

Racial/Ethnic Threat and Federal Sentencing

This study examines whether federal sentencing decisions are influenced by the racial/ethnic composition of federal court districts. Multilevel models of individual cases within federal judicial districts show that black defendants receive moderately longer sentences than whites, and that Hispanics and whites receive similar sentences. These race/ethnicity effects on sentence length are found to vary across federal districts, but not as predicted by racial threat theory. In contrast to racial threat predictions, black sentence lengths are not significantly conditioned by the district black population. Contrary to racial threat predictions, Hispanic defendants receive the harshest sentences when they account for the smallest share of the population (1-3 percent) and the most lenient sentences when they make up more sizable shares of district populations (more than 27 percent). Our results indicate that racial threat theory provides an inadequate explanation of how social contexts influence the federal sentencing of blacks and Hispanics

Discretion and Disparity under Sentencing Guidelines Revisited: The Interrelationship between Structured Sentencing Alternatives and Guideline Decision-making

Objectives: We argue that the reasons court actors conform to or depart from sentencing guideline recommendations likely vary depending on whether the decision involves an alternative sanction or incarceration and that these reasons may have consequences for ethnoracial disparities in the sentencing of defendants and how these disparities are understood. Method: We use recent (2012–2016) Pennsylvania sentencing data to examine (1) the relationship between defendant race/ethnicity and court actors’ decisions to depart downward and upward from the guidelines and (2) whether such relationships vary depending on whether they involve an alternative sanction, namely intermediate punishments (IPs). Results: We find that the association of defendant race/ethnicity with decisions to conform to the guidelines or to depart is greatly impacted by whether the sentence involves an IP. Blacks and, to a lesser extent, Latinos experienced greater disadvantage in guideline decision-making, whether conformity or departures, when the sentence involved an IP. Conclusions: Results suggest that the integration of IP into guideline systems may have (1) mobilized ethnoracial disparities in sentencing, (2) focused the location of sentencing disparities to sentences involving IP, and (3) changed the applicability of common interpretations of guideline decisions and disparities in their imposition

Sentencing guidelines : lessons from Pennsylvania

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Organizational Conformity and Punishment: Federal Court Communities and Judge-Initiated Guidelines Departures

The U.S. Sentencing Guidelines represent a uniform set of formal rules that are implemented across a broad range of diverse social contexts. Drawing from neo-institutional theory and kindred perspectives on criminal courts, we argue that the federal courts represent an organizational field in which local influences play a key role in conformity to institutional rules. We use unique survey data from federal judges, aggregated to the district court level and combined with individual-level federal sentencing data, to examine hierarchical models of judicial departures from the Guidelines. Our analysis includes more proximate measures of court community culture than prior research. We find that the collective views of federal judges, including their perceptions of the degree of regulative constraint posed by the Guidelines, as well as the extent to which the Guidelines are normatively and morally legitimate, are intimately related to variation in judicial Guidelines departures across district courts