Accurate prediction by AlphaFold2 for ligand binding in a reductive dehalogenase and implications for PFAS (per- and polyfluoroalkyl substance) biodegradation.

Despite the success of AlphaFold2 (AF2), it is unclear how AF2 models accommodate for ligand binding. Here, we start with a protein sequence from Acidimicrobiaceae TMED77 (T7RdhA) with potential for catalyzing the degradation of per- and polyfluoroalkyl substances (PFASs). AF2 models and experiments identified T7RdhA as a corrinoid iron-sulfur protein (CoFeSP) which uses a norpseudo-cobalamin (BVQ) cofactor and two Fe4S4 iron-sulfur clusters for catalysis. Docking and molecular dynamics simulations suggest that T7RdhA uses perfluorooctanoic acetate (PFOA) as a substrate, supporting the reported defluorination activity of its homolog, A6RdhA. We showed that AF2 provides processual (dynamic) predictions for the binding pockets of ligands (cofactors and/or substrates). Because the pLDDT scores provided by AF2 reflect the protein native states in complex with ligands as the evolutionary constraints, the Evoformer network of AF2 predicts protein structures and residue flexibility in complex with the ligands, i.e., in their native states. Therefore, an apo-protein predicted by AF2 is actually a holo-protein awaiting ligands.

Diffractive deep neural network adjoint assist or (DNA)2: a fast and efficient nonlinear diffractive neural network implementation.

The recent advent of diffractive deep neural networks or D2NNs has opened new avenues for the design and optimization of multi-functional optical materials; despite the effectiveness of the D2NN approach, there is a need for making these networks as well as the design algorithms more general and computationally efficient. The work demonstrated in this paper brings significant improvements to both these areas by introducing an algorithm that performs inverse design on fully nonlinear diffractive deep neural network - assisted by an adjoint sensitivity analysis which we term (DNA)2. As implied by the name, the procedure optimizes the parameters associated with the diffractive elements including both linear and nonlinear amplitude and phase contributions as well as the spacing between planes via adjoint sensitivity analysis. The computation of all gradients can be obtained in a single GPU compatible step. We demonstrate the capability of this approach by designing several types of three layered D2NN to classify 8800 handwritten digits taken from the MNIST database. In all cases, the D2NN was able to achieve a minimum 94.64% classification accuracy with 192 minutes or less of training.

The entropic bond in colloidal crystals.

A vast array of natural phenomena can be understood through the long-established schema of chemical bonding. Conventional chemical bonds arise through local gradients resulting from the rearrangement of electrons; however, it is possible that the hallmark features of chemical bonding could arise through local gradients resulting from nonelectronic forms of mediation. If other forms of mediation give rise to "bonds" that act like conventional ones, recognizing them as bonds could open new forms of supramolecular descriptions of phenomena at the nano- and microscales. Here, we show via a minimal model that crowded hard-particle systems governed solely by entropy exhibit the hallmark features of bonding despite the absence of chemical interactions. We quantitatively characterize these features and compare them to those exhibited by chemical bonds to argue for the existence of entropic bonds. As an example of the utility of the entropic bond classification, we demonstrate the nearly equivalent tradeoff between chemical bonds and entropic bonds in the colloidal crystallization of hard hexagonal nanoplates.

Hierarchical self-assembly of hard cube derivatives.

Hierarchical, self-assembled structures are ordered on multiple scales, and formed by objects comprised of even smaller elements. Such structures are widely reported for nanoparticles, macromolecules, and peptides, and even in entropy-driven hard particle assembly hierarchical colloidal crystals have been reported. Here we consider the hierarchical self-assembly of a cubic colloidal crystal from congruent hard cube derivatives, and investigate how various ways of slicing and dicing a cube can affect the ability of the pieces to entropically re-assemble the initial colloidal crystal formed from perfect cubes. We present design rules that support heuristics reported for different systems, and present evidence for a previously unreported cubatic phase from 2 : 1 rectangular prisms.

Shape allophiles improve entropic assembly.

We investigate a class of "shape allophiles" that fit together like puzzle pieces as a method to access and stabilize desired structures by controlling directional entropic forces. Squares are cut into rectangular halves, which are shaped in an allophilic manner with the goal of re-assembling the squares while self-assembling the square lattice. We examine the assembly characteristics of this system via the potential of mean force and torque, and the fraction of particles that entropically bind. We generalize our findings and apply them to self-assemble triangles into a square lattice via allophilic shaping. Through these studies we show how shape allophiles can be useful for assembling and stabilizing desired phases with appropriate allophilic design.

Human rights abuses and collective resilience among sex workers in four African countries: a qualitative study.

BACKGROUND: Sex work is a criminal offence, virtually throughout Africa. This criminalisation and the intense stigma attached to the profession shapes interactions between sex workers and their clients, family, fellow community members, and societal structures such as the police and social services. METHODS: We explore the impact of violence and related human rights abuses on the lives of sex workers, and how they have responded to these conditions, as individuals and within small collectives. These analyses are based on data from 55 in-depth interviews and 12 focus group discussions with female, male and transgender sex workers in Kenya, South Africa, Uganda and Zimbabwe. Data were collected by sex worker outreach workers trained to conduct qualitative research among their peers. RESULTS: In describing their experiences of unlawful arrests and detention, violence, extortion, vilification and exclusions, participants present a picture of profound exploitation and repeated human rights violations. This situation has had an extreme impact on the physical, mental and social wellbeing of this population. Overall, the article details the multiple effects of sex work criminalisation on the everyday lives of sex workers and on their social interactions and relationships. Underlying their stories, however, are narratives of resilience and resistance. Sex workers in our study draw on their own individual survival strategies and informal forms of support and very occasionally opt to seek recourse through formal channels. They generally recognize the benefits of unified actions in assisting them to counter risks in their environment and mobilise against human rights violations, but note how the fluctuant and stigmatised nature of their profession often undermines collective action. CONCLUSIONS: While criminal laws urgently need reform, supporting sex work self-organisation and community-building are key interim strategies for safeguarding sex workers' human rights and improving health outcomes in these communities. If developed at sufficient scale and intensity, sex work organisations could play a critical role in reducing the present harms caused by criminalisation and stigma.

'We are despised in the hospitals': sex workers' experiences of accessing health care in four African countries.

Sex workers in east and southern Africa are exposed to multiple occupational health and safety risks. Detailed understanding of barriers to accessing care would optimise design of improved services for this population. In this study, trained sex workers conducted 55 in-depth interviews and 12 focus group discussions with 106 female, 26 male and 4 transgender sex workers across 6 urban sites in Kenya, Zimbabwe, Uganda and South Africa. Data were analysed thematically, following an interpretive framework. Participants cited numerous unmet health needs, including diagnosis and treatment for sexually transmitted infections and insufficient access to condoms and lubricant. Denial of treatment for injuries following physical assault or rape and general hostility from public-sector providers was common. Resources permitting, many sex workers attended private services, citing higher quality and respect for dignity and confidentiality. Sex workers in southern Africa accessed specialised sex worker clinics, reporting mostly positive experiences. Across sites, participants called for additional targeted services, but also sensitisation and training of public-sector providers. Criminalisation of sex workers and associated stigmatisation, particularly of transgender and male sex workers, hinder HIV-prevention efforts and render access to mainstream healthcare precarious. Alongside law reform, sex worker-led peer outreach work should be strengthened and calls by sex workers for additional targeted services heeded.