Evidence against the Detectability of a Hippocampal Place Code Using Functional Magnetic Resonance Imaging

Individual hippocampal neurons selectively increase their firing rates in specific spatial locations. As a population, these neurons provide a decodable representation of space that is robust against changes to sensory- and path-related cues. This neural code is sparse and distributed, theoretically rendering it undetectable with population recording methods such as functional magnetic resonance imaging (fMRI). Existing studies nonetheless report decoding spatial codes in the human hippocampus using such techniques. Here we present results from a virtual navigation experiment in humans in which we eliminated visual- and path-related confounds and statistical limitations present in existing studies, ensuring that any positive decoding results would represent a voxel-place code. Consistent with theoretical arguments derived from electrophysiological data and contrary to existing fMRI studies, our results show that although participants were fully oriented during the navigation task, there was no statistical evidence for a place code

Rapid optimization of gene dosage in E. coli using DIAL strains

<p>Abstract</p> <p>Background</p> <p>Engineers frequently vary design parameters to optimize the behaviour of a system. However, synthetic biologists lack the tools to rapidly explore a critical design parameter, gene expression level, and have no means of systematically varying the dosage of an entire genetic circuit. As a step toward overcoming this shortfall, we have developed a technology that enables the same plasmid to be maintained at different copy numbers in a set of closely related cells. This provides a rapid method for exploring gene or cassette dosage effects.</p> <p>Results</p> <p>We engineered two sets of strains to constitutively provide a <it>trans</it>-acting replication factor, either Pi of the R6K plasmid or RepA of the ColE2 plasmid, at different doses. Each DIAL (different allele) strain supports the replication of a corresponding plasmid at a constant level between 1 and 250 copies per cell. The plasmids exhibit cell-to-cell variability comparable to other popular replicons, but with improved stability. Since the origins are orthogonal, both replication factors can be incorporated into the same cell. We demonstrate the utility of these strains by rapidly assessing the optimal expression level of a model biosynthetic pathway for violecein.</p> <p>Conclusions</p> <p>The DIAL strains can rapidly optimize single gene expression levels, help balance expression of functionally coupled genetic elements, improve investigation of gene and circuit dosage effects, and enable faster development of metabolic pathways.</p

On Measuring Fairness in Generative Models

Recently, there has been increased interest in fair generative models. In this work, we conduct, for the first time, an in-depth study on fairness measurement, a critical component in gauging progress on fair generative models. We make three contributions. First, we conduct a study that reveals that the existing fairness measurement framework has considerable measurement errors, even when highly accurate sensitive attribute (SA) classifiers are used. These findings cast doubts on previously reported fairness improvements. Second, to address this issue, we propose CLassifier Error-Aware Measurement (CLEAM), a new framework which uses a statistical model to account for inaccuracies in SA classifiers. Our proposed CLEAM reduces measurement errors significantly, e.g., 4.98% $\rightarrow$ 0.62% for StyleGAN2 w.r.t. Gender. Additionally, CLEAM achieves this with minimal additional overhead. Third, we utilize CLEAM to measure fairness in important text-to-image generator and GANs, revealing considerable biases in these models that raise concerns about their applications. Code and more resources: https://sutd-visual-computing-group.github.io/CLEAM/.Comment: Accepted in NeurIPS2

SYNTHESIS OF COMPLEX INORGANIC COLLOIDAL HOLLOW NANOSCALED ARCHITECTURES AND ITS APPLICATION

Ph.DDOCTOR OF PHILOSOPH

Young people’s perceptions of advice about sexual risk taking

Sexual and reproductive health indicators for young people in the USA have improved in recent decades, but teenage pregnancies remain high, and large differences between Whites and non-Whites persist in teenage births, abortions, and the acquisition of sexually transmitted infections. Prior research shows that young people are receptive to communication about sex from parents and friends, but peers have been found to be more influential on sexual risk taking. In this study of 617 young people aged 13–20 years in high-risk neighbourhoods for teenage pregnancy in New Jersey, we asked whether sexually inexperienced young people differed from sexually experienced young people in their level of receptivity to the recommendations from their parents, friends, and others about whether to have sex before marriage and whether to use a condom if sexually active. The results showed that the sexually inexperienced were more receptive to messages from figures of authority in their life than those sexually experienced. We also found that stronger message intensity from parents, friends, and others to delay sex until marriage and to use a condom if sexually active was associated with lower sexual intentions in the next six months and the use of a condom if sexually active in the last three months

Binary Condensation in a Supersonic Nozzle

We present data from the first systematic studies of binary condensation in supersonic nozzles. The apparatus used to conduct the experiments is described in detail, and the important issues of stability and reproducibility of the experiments are discussed. Experiments were conducted with water, ethanol, propanol, and binary mixtures of these compounds. Onset was determined in the temperature range of 190-215 K, and for each mixture composition the pressures of the condensible species at an onset temperature of 207 K were determined. For the ideal ethanol-propanol mixtures, the onset pressures at constant temperature vary almost linearly between those of the pure components. In contrast the isothermal onset pressures for the nonideal water-ethanol and water-propanol mixtures lie below the straight line joining the pure component values. This large reduction in the total pressure of condensible at onset for the aqueous alcohol mixtures is indicative of a strong mutual enhancement in the particle formation process

Structurally confined influenza subunit vaccines in the prefusion conformation elicit a potent neutralizing antibody response

Effective vaccination against influenza viruses remains a significant global challenge. Despite ongoing efforts, continual antigenic changes in circulating viruses requires constant update of existing vaccine approaches. Furthermore, the majority of current licensed vaccines are derivatives of live virus and are inherently time consuming to produce and limit the potential response time to counter a new virus strain. However, the combined advances in subunit vaccine production and structural determination of critical neutralizing epitopes within influenza hemagglutinin (HA) provide the groundwork for the next generation of influenza vaccines which have the potential to overcome these limitations. In an effort to expand on these findings we have compared the effectiveness of both prefusion and postfusion forms of recombinant influenza hemagglutinin (rHA) as subunit vaccines. Using a novel stabilization tag to confine rHA in the prefusion conformation we demonstrated that while both HA conformations elicit anti-HA responses in mice, a neutralizing response (PRNT50 1:36000) is only observed for prefusion rHA. Using rHAs from a range of influenza subtypes and domain specific constructs together with a large panel of structurally defined antibodies we also examined the epitope specificity and cross-reactivity of the prefusion specific neutralizing response. Interestingly, a similar conformation dependence has been reported for respiratory syncytial virus1, 2, suggesting a universal strategy for the generation of potent subunit vaccines to target enveloped viruses. 1. Magro, M. et al. Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci U S A 109, 3089-3094 (2012). 2. McLellan, J.S. et al. Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus. Science 342, 592-598 (2013)

A pre-fusion, trimeric subunit influenza HA-based vaccine elicits cross-protection between highly divergent influenza A viruses

Despite our best efforts to vaccinate against influenza viruses they remain a major cause of morbidity and mortality worldwide, resulting in 3-5 million severe infections and more than 250,000 deaths annually. Constant antigenic changes in circulating viruses means current vaccines must be updated and re-administered annually. This approach is time-consuming and expensive, and is often hindered by mismatches between circulating and vaccine strains. Strain mismatch can contribute to insufficient vaccine efficacy, which has ranged from just 10-60% over the last decade. Furthermore, recent sporadic zoonotic outbreaks of novel highly pathogenic viruses from avian species, to which current vaccines provide no immunity, have been observed, with fatality rates around 40%. This raises serious concerns of a global pandemic with the potential to spread rapidly before a vaccine can be manufactured. Novel approaches to influenza vaccination are clearly needed in order to overcome these limitations with “universal” flu vaccines being the holy grail. We have stabilized recombinant influenza haemagglutinin (rHA) in its native, pre-fusion conformation by the addition of a novel “clamp” stabilization motif to enhance subunit vaccine potency and breadth of protection. Immunisation of mice with clamp-stabilized prefusion rHA elicited a potent neutralizing antibody response (~4-fold improvement over current vaccines). Most importantly, antibodies elicited upon immunisation with clamp-stabilised prefusion rHA showed an 80-fold increase in cross-reactivity to rHA derived from a divergent, highly pathogenic avian virus (H5N1) when compared to the current influenza vaccines. We have also shown that vaccination with clamp-stabilisted rHA based on the H3 subtype (group 2) is capable of providing cross-protection to a challenge with a highly-divergent group 1 virus (H1N1). Ultimately, this approach could represent a potential universal influenza vaccine, providing enhanced cross-protection against both group 1 and 2 seasonal influenza virus strains while simultaneously providing an increased cross-reactive humoral immune response to potential zoonotic pandemic strains. Please click Additional Files below to see the full abstract