Consensus Protein Design without Phylogenetic Bias

Consensus design is an appealing strategy for the stabilization of proteins. It exploits amino acid conservation in sets of homologous proteins to identify likely beneficial mutations. Nevertheless, its success depends on the phylogenetic diversity of the sequence set available. Here, we show that randomization of a single protein represents a reliable alternative source of sequence diversity that is essentially free of phylogenetic bias. A small number of functional protein sequences selected from binary-patterned libraries suffice as input for the consensus design of active enzymes that are easier to produce and substantially more stable than individual members of the starting data set. Although catalytic activity correlates less consistently with sequence conservation in these extensively randomized proteins, less extreme mutagenesis strategies might be adopted in practice to augment stability while maintaining function

Robustness of Equations Under Operational Extensions

Sound behavioral equations on open terms may become unsound after conservative extensions of the underlying operational semantics. Providing criteria under which such equations are preserved is extremely useful; in particular, it can avoid the need to repeat proofs when extending the specified language. This paper investigates preservation of sound equations for several notions of bisimilarity on open terms: closed-instance (ci-)bisimilarity and formal-hypothesis (fh-)bisimilarity, both due to Robert de Simone, and hypothesis-preserving (hp-)bisimilarity, due to Arend Rensink. For both fh-bisimilarity and hp-bisimilarity, we prove that arbitrary sound equations on open terms are preserved by all disjoint extensions which do not add labels. We also define slight variations of fh- and hp-bisimilarity such that all sound equations are preserved by arbitrary disjoint extensions. Finally, we give two sets of syntactic criteria (on equations, resp. operational extensions) and prove each of them to be sufficient for preserving ci-bisimilarity.Comment: In Proceedings EXPRESS'10, arXiv:1011.601

Flexible Lipid Bilayers in Implicit Solvent

A minimalist simulation model for lipid bilayers is presented. Each lipid is represented by a flexible chain of beads in implicit solvent. The hydrophobic effect is mimicked through an intermolecular pair potential localized at the ``water''/hydrocarbon tail interface. This potential guarantees realistic interfacial tensions for lipids in a bilayer geometry. Lipids self assemble into bilayer structures that display fluidity and elastic properties consistent with experimental model membrane systems. Varying molecular flexibility allows for tuning of elastic moduli and area/molecule over a range of values seen in experimental systems.Comment: 5 pages, 5 figure

Measurements of iron status and survival in African iron overload

No Abstract

Applications of artificial intelligence to prostate multiparametric MRI (mpMRI): Current and emerging trends

Prostate carcinoma is one of the most prevalent cancers worldwide. Multiparametric magnetic resonance imaging (mpMRI) is a non-invasive tool that can improve prostate lesion detection, classification, and volume quantification. Machine learning (ML), a branch of artificial intelligence, can rapidly and accurately analyze mpMRI images. ML could provide better standardization and consistency in identifying prostate lesions and enhance prostate carcinoma management. This review summarizes ML applications to prostate mpMRI and focuses on prostate organ segmentation, lesion detection and segmentation, and lesion characterization. A literature search was conducted to find studies that have applied ML methods to prostate mpMRI. To date, prostate organ segmentation and volume approximation have been well executed using various ML techniques. Prostate lesion detection and segmentation are much more challenging tasks for ML and were attempted in several studies. They largely remain unsolved problems due to data scarcity and the limitations of current ML algorithms. By contrast, prostate lesion characterization has been successfully completed in several studies because of better data availability. Overall, ML is well situated to become a tool that enhances radiologists\u27 accuracy and speed

“I Felt Like a Superhero”: The Experience of Responding to Drug Overdose Among Individuals Trained in Overdose Prevention

BACKGROUND: Overdose prevention programs (OPPs) train people who inject drugs and other community members to prevent, recognise and respond to opioid overdose. However, little is known about the experience of taking up the role of an overdose responder for the participants. METHODS: We present findings from qualitative interviews with 30 participants from two OPPs in Los Angeles, CA, USA from 2010 to 2011 who had responded to at least one overdose since being trained in overdose prevention and response. RESULTS: Being trained by an OPP and responding to overdoses had both positive and negative effects for trained responders . Positive effects include an increased sense of control and confidence, feelings of heroism and pride, and a recognition and appreciation of one\u27s expertise. Negative effects include a sense of burden, regret, fear, and anger, which sometimes led to cutting social ties, but might also be mitigated by the increased empowerment associated with the positive effects. CONCLUSION: Findings suggest that becoming an overdose responder can involve taking up a new social role that has positive effects, but also confers some stress that may require additional support. OPPs should provide flexible opportunities for social support to individuals making the transition to this new and critical social role. Equipping individuals with the skills, technology, and support they need to respond to drug overdose has the potential to confer both individual and community-wide benefits

Projection on Segre varieties and determination of holomorphic mappings between real submanifolds

It is shown that a germ of a holomorphic mapping sending a real-analytic generic submanifold of finite type into another is determined by its projection on the Segre variety of the target manifold. A necessary and sufficient condition is given for a germ of a mapping into the Segre variety of the target manifold to be the projection of a holomorphic mapping sending the source manifold into the target. An application to the biholomorphic equivalence problem is also given.Comment: 16 page

Slow-Speed Supernovae from the Palomar Transient Factory: Two Channels

Since the discovery of the unusual prototype SN 2002cx, the eponymous class of low-velocity, hydrogen-poor supernovae has grown to include at most another two dozen members identified from several heterogeneous surveys, in some cases ambiguously. Here we present the results of a systematic study of 1077 hydrogen-poor supernovae discovered by the Palomar Transient Factory, leading to nine new members of this peculiar class. Moreover we find there are two distinct subclasses based on their spectroscopic, photometric, and host galaxy properties: The "SN 2002cx-like" supernovae tend to be in later-type or more irregular hosts, have more varied and generally dimmer luminosities, have longer rise times, and lack a Ti II trough when compared to the "SN 2002es-like" supernovae. None of our objects show helium, and we counter a previous claim of two such events. We also find that these transients comprise 5.6+17-3.7% (90% confidence) of all SNe Ia, lower compared to earlier estimates. Combining our objects with the literature sample, we propose that these subclasses have two distinct physical origins.Comment: 49 pages, 36 figures, submitted to Ap

Type II Supernovae as Probes of Cosmology

- Constraining the cosmological parameters and understanding Dark Energy have tremendous implications for the nature of the Universe and its physical laws. - The pervasive limit of systematic uncertainties reached by cosmography based on Cepheids and Type Ia supernovae (SNe Ia) warrants a search for complementary approaches. - Type II SNe have been shown to offer such a path. Their distances can be well constrained by luminosity-based or geometric methods. Competing, complementary, and concerted efforts are underway, to explore and exploit those objects that are extremely well matched to next generation facilities. Spectroscopic follow-up will be enabled by space- based and 20-40 meter class telescopes. - Some systematic uncertainties of Type II SNe, such as reddening by dust and metallicity effects, are bound to be different from those of SNe Ia. Their stellar progenitors are known, promising better leverage on cosmic evolution. In addition, their rate - which closely tracks the ongoing star formation rate - is expected to rise significantly with look- back time, ensuring an adequate supply of distant examples. - These data will competitively constrain the dark energy equation of state, allow the determination of the Hubble constant to 5%, and promote our understanding of the processes involved in the last dramatic phases of massive stellar evolution.Comment: Science white paper, submitted to the Decadal committee Astro201

An Early and Comprehensive Millimetre and Centimetre Wave and X-ray Study of SN 2011dh: a Non-Equipartition Blast Wave Expanding into a Massive Stellar Wind

Only a handful of supernovae (SNe) have been studied in multiwavelengths from the radio to X-rays, starting a few days after the explosion. The early detection and classification of the nearby Type IIb SN 2011dh/PTF 11eon in M51 provides a unique opportunity to conduct such observations. We present detailed data obtained at one of the youngest phase ever of a core-collapse SN (days 3–12 after the explosion) in the radio, millimetre and X-rays; when combined with optical data, this allows us to explore the early evolution of the SN blast wave and its surroundings. Our analysis shows that the expanding SN shock wave does not exhibit equipartition (ϵe/ϵB ∼ 1000), and is expanding into circumstellar material that is consistent with a density profile falling like R−2. Within modelling uncertainties we find an average velocity of the fast parts of the ejecta of 15 000 ± 1800 km s−1, contrary to previous analysis. This velocity places SN 2011dh in an intermediate blast wave regime between the previously defined compact and extended SN Type IIb subtypes. Our results highlight the importance of early (∼1 d) high-frequency observations of future events. Moreover, we show the importance of combined radio/X-ray observations for determining the microphysics ratio ϵe/ϵB