Crimes Defining Our Time: Notable Criminal Cases from the First Fifty Years of the Middle Distric of Florida

Since the inception of the Middle District of Florida in 1962, the breadth of cases prosecuted in the District during the first five decades has covered the spectrum of the federal criminal code. The courthouses in the District have certainly housed many nationally significant and high profile cases, all worthy of extensive discussion and debate. Given the nature and scope of the many significant prosecutions, it is a difficult task to select just a few notable criminal cases. The nine cases discussed below have not been selected based upon the success of the government or defense in the case, but rather have been selected to be briefly summarized based upon the nature of the charges and the national significance of the prosecution

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Social Closeness and Feedback Modulate Susceptibility to the Framing Effect

Although we often seek social feedback (SFB) from others to help us make decisions, little is known about how SFB affects decisions under risk, particularly from a close peer. We conducted two experiments using an established framing task to probe how decision-making is modulated by SFB valence (positive, negative) and the level of closeness with feedback provider (friend, confederate). Participants faced mathematically equivalent decisions framed as either an opportunity to keep (gain frame) or lose (loss frame) part of an initial endowment. Periodically, participants were provided with positive (e.g., “Nice!”) or negative (e.g., “Lame!”) feedback about their choices. Such feedback was provided by either a confederate (Experiment 1) or a gender-matched close friend (Experiment 2). As expected, the framing effect was observed in both experiments. Critically, an individual\u27s susceptibility to the framing effect was modulated by the valence of the SFB, but only when the feedback provider was a close friend. This effect was reflected in the activation patterns of ventromedial prefrontal cortex and posterior cingulate cortex, regions involved in complex decision-making. Taken together, these results highlight social closeness as an important factor in understanding the impact of SFB on neural mechanisms of decision-making

CD1a on Langerhans cells controls inflammatory skin disease

CD1a is a lipid-presenting molecule that is abundantly expressed on Langerhans cells. However, the in vivo role of CD1a has remained unclear, principally because CD1a is lacking in mice. Through the use of mice with transgenic expression of CD1a, we found that the plant-derived lipid urushiol triggered CD1a-dependent skin inflammation driven by CD4+ helper T cells that produced the cytokines IL-17 and IL-22 (TH17 cells). Human subjects with poison-ivy dermatitis had a similar cytokine signature following CD1a-mediated recognition of urushiol. Among various urushiol congeners, we identified diunsaturated pentadecylcatechol (C15:2) as the dominant antigen for CD1a-restricted T cells. We determined the crystal structure of the CD1a-urushiol (C15:2) complex, demonstrating the molecular basis of urushiol interaction with the antigen-binding cleft of CD1a. In a mouse model and in patients with psoriasis, CD1a amplified inflammatory responses that were mediated by TH17 cells that reacted to self lipid antigens. Treatment with blocking antibodies to CD1a alleviated skin inflammation. Thus, we propose CD1a as a potential therapeutic target in inflammatory skin diseases

An FPGA-based bolometer for the MAST-U Super-X divertor

A new resistive bolometer system has been developed for MAST-Upgrade. It will measure radiated power in the new Super-X divertor, with millisecond time resolution, along 16 vertical and 16 horizontal lines of sight. The system uses a Xilinx Zynq-7000 series Field-Programmable Gate Array (FPGA) in the D-TACQ ACQ2106 carrier to perform real time data acquisition and signal processing. The FPGA enables AC-synchronous detection using high performance digital filtering to achieve a high signal-to-noise ratio and will be able to output processed data in real time with millisecond latency. The system has been installed on 8 previously unused channels of the JET vertical bolometer system. Initial results suggest good agreement with data from existing vertical channels but with higher bandwidth and signal-to-noise ratio

Evolution of genes and genomes on the Drosophila phylogeny

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species