Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In \'I: framing family medicine-history, values, and perspectives\', the authors address the following themes: \'Notes on Storylines of Family Medicine\', \'Family medicine-the generalist specialty\', \'Family medicine\'s achievements-a glass half full assessment\', \'Family medicine\'s next 50 years-toward filling our glasses\', \'Four enduring truths of family medicine\', \'Names matter\', \'Family medicine at its core\' and \'The ecology of medical care.\' May readers find much food for thought in these essays.

BACKGROUND: Retrosynthesis is a critical task in drug discovery, aimed at finding a viable pathway for synthesizing a given target molecule. Many existing approaches frame this task as a graph-generating problem. Specifically, these methods first identify the reaction center, and break a targeted molecule accordingly to generate the synthons. Reactants are generated by either adding atoms sequentially to synthon graphs or by directly adding appropriate leaving groups. However, both of these strategies have limitations. Adding atoms results in a long prediction sequence that increases the complexity of generation, while adding leaving groups only considers those in the training set, which leads to poor generalization.
RESULTS: In this paper, we propose a novel end-to-end graph generation model for retrosynthesis prediction, which sequentially identifies the reaction center, generates the synthons, and adds motifs to the synthons to generate reactants. Given that chemically meaningful motifs fall between the size of atoms and leaving groups, our model achieves lower prediction complexity than adding atoms and demonstrates superior performance than adding leaving groups. We evaluate our proposed model on a benchmark dataset and show that it significantly outperforms previous state-of-the-art models. Furthermore, we conduct ablation studies to investigate the contribution of each component of our proposed model to the overall performance on benchmark datasets. Experiment results demonstrate the effectiveness of our model in predicting retrosynthesis pathways and suggest its potential as a valuable tool in drug discovery.
METHODS: All code and data are available at https://github.com/szu-ljh2020/MARS.

Real time parameter measurement cannot be carried out to dynamic ring parts during automation ring rolling processes so that rolling process parameters cannot be adjusted in time. Considering effects of shaping of ring rolling parts, a visual measurement platform was set up and a machine vision-based non-contact real -time measurement method was put forward. This article improves the subpixel level edge extraction algorithm to extract edge data information of circular rolling pieces. Based on the characteristics of circular rolling pieces, an RG-Hough transform method is proposed to fit the detected edge data information. The conversion relationship between pixel and actual sizes were determined in combination with the camera calibration to gain parameters of ring rolling parts. Measurements of ring parts (OD: 462.12mm; and ID: 315.53mm) were applied to verify the effectiveness of our method. Our measurement error is ±0.25mm and our average speed can be up to 104ms/frame. Our study can provide powerful technical supports for intelligent control of ring rolling pieces.

Previous research has extensively investigated why users spread misinformation online, while less attention has been given to the motivations behind sharing fact-checks. This article reports a four-country survey experiment assessing the influence of confirmation and refutation frames on engagement with online fact-checks. Respondents randomly received semantically identical content, either affirming accurate information (\"It is TRUE that p\") or refuting misinformation (\"It is FALSE that not p\"). Despite semantic equivalence, confirmation frames elicit higher engagement rates than refutation frames. Additionally, confirmation frames reduce self-reported negative emotions related to polarization. These findings are crucial for designing policy interventions aiming to amplify fact-check exposure and reduce affective polarization, particularly in critical areas such as health-related misinformation and harmful speech.

A chain formation strategy based on mobile frames for a set of n differential drive mobile robots is presented. Considering two consecutive robots in the formation, robots Ri and Ri+1. It is intended that robot Ri+1 follows the delayed trajectory, τ units of time, of the leader robot Ri. In this way, the follower robot Ri+1 becomes the leader robot for robot Ri+ 2 in the formation and so on. With this formation policy, the trailing distance between two consecutive robots varies accordingly to the velocity of the Ri leader robot. Mobile frames are located on the body of the vehicles, in such a way that the position of robot Ri is determined with respect to the frame located on Ri+1 robot. The strategy relies on the fact that the general leader robot R1 describes any trajectory generated by bounded linear v1(t) and angular ω1(t) velocities. For the remaining vehicles in the string, the strategy considers a desired trajectory for the follower robot Ri+1 obtained by an estimation of the delayed trajectory of the leader robot Ri. This desired estimated trajectory is obtained under the knowledge of the actual and past input velocities of the Ri robot. To formally prove the convergence of the formation strategy, the equations describing the time variation of the relative posture between any pair of consecutive vehicles in the formation are obtained, and a feedback law based on local measurements is proposed to get the convergence of robot Ri+1 to the delayed trajectory, τ units of time, of the trajectory previously described by robot Ri. Lyapunov techniques are considered for this fact. The effectiveness of the chain formation solution is evaluated by means of numerical simulations and real time experiments showing an adequate convergence.

While undergoing structural deformation, DNA experiences changes in the interactions between its internal base pairs, presenting challenges to conventional elastic methods. To address this, we propose the Discrete Critical State (DCS) model in this paper. This model combines surface discrete frame theory with gauge theory and Landau phase transition theory to investigate DNA\'s structural deformation, phase transitions, and chirality. Notably, the DCS model considers both the internal interactions within DNA and formulates an overall equation using unified physical and geometric parameters. By employing the discrete frame, we derive the evolution of physical quantities along the helical axis of DNA, including geodesic curvature, geodesic torsion, and others. Our findings indicate that B-DNA has a significantly lower free energy density compared to Z-DNA, which is in agreement with experimental observations. This research reveals that the direction of base pairs is primarily governed by the geodesic curve within the helical plane, aligning closely with the orientation of the base pairs. Moreover, the geodesic curve has a profound influence on the arrangement of base pairs at the microscopic level and effectively regulates the configuration and geometry of DNA through macroscopic-level free energy considerations.

Upstream open reading frames (uORFs) are a frequent feature of eukaryotic mRNAs. Upstream ORFs govern main ORF translation in a variety of ways, but, in a nutshell, they either filter out scanning ribosomes or allow downstream translation initiation via leaky scanning or reinitiation. Previous reports concurred that eIF4G2, a long-known but insufficiently studied eIF4G1 homologue, can rescue the downstream translation, but disagreed on whether it is leaky scanning or reinitiation that eIF4G2 promotes. Here, we investigated a unique human mRNA that encodes two highly conserved proteins (POLGARF with unknown function and POLG, the catalytic subunit of the mitochondrial DNA polymerase) in overlapping reading frames downstream of a regulatory uORF. We show that the uORF renders the translation of both POLGARF and POLG mRNAs reliant on eIF4G2. Mechanistically, eIF4G2 enhances both leaky scanning and reinitiation, and it appears that ribosomes can acquire eIF4G2 during the early steps of reinitiation. This emphasizes the role of eIF4G2 as a multifunctional scanning guardian that replaces eIF4G1 to facilitate ribosome movement but not ribosome attachment to an mRNA.

I use the clinical example of a traumatized adolescent to talk about how a transference experience creates the frame where the analytic work occurs. Out of the external boundaries of the relationships with an object, the internal frame, the womb of transformation processes, is created. The analyst\'s capacity to wait is essential for the transformation that creates and shapes the transference experience, which, like playing, becomes the matrix of the frame where it happens as it happens. As the traumatic experiences find their place in the transference and begin to be integrated, the adolescent becomes more present and real in the session.

Google proposed a new TCP congestion control algorithm (CCA), Bottleneck Bandwidth and Round-trip propagation time (BBR) which has opened up new dimensions in congestion control. BBR tries to operate near Kleinrock\'s operating point to avoid excessive queue formation at the bottleneck and to use the link bandwidth optimally. BBR creates a model of the network path by measuring the bottleneck bandwidth and minimum round-trip time (RTT) to maximize the delivery rate and minimize latency. BBR v2 is an updated version of BBR which addresses many shortcomings of the original BBR (BBR v1) such as interprotocol fairness, RTT fairness, and excessive retransmissions. However, BBR v2 has certain limitations in its operation in IEEE 802.11ac (Wi-Fi 5) networks. The default BBR v2 limits the throughput of Wi-Fi 5 and an increased latency has been observed. This is because the Wi-Fi 5 frame aggregation logic is underutilized and fewer frames are being sent to the Wi-Fi 5 interface. In this paper, we have proposed BBR-n (BBR new) which provides better throughput than the generic BBR v2 in the Wi-Fi 5 networks. Real-time experiments were performed over a physical testbed using Flent to confirm that BBR-n achieves over double throughput as compared to generic BBR v2 and reduced latency in networks as compared to pure loss-based variants such as Cubic and Reno.

One of the most critical steps of protein synthesis is coupled translocation of messenger RNA (mRNA) and transfer RNAs (tRNAs) required to advance the mRNA reading frame by one codon. In eukaryotes, translocation is accelerated and its fidelity is maintained by elongation factor 2 (eEF2)1,2. At present, only a few snapshots of eukaryotic ribosome translocation have been reported3-5. Here we report ten high-resolution cryogenic-electron microscopy (cryo-EM) structures of the elongating eukaryotic ribosome bound to the full translocation module consisting of mRNA, peptidyl-tRNA and deacylated tRNA, seven of which also contained ribosome-bound, naturally modified eEF2. This study recapitulates mRNA-tRNA2-growing peptide module progression through the ribosome, from the earliest states of eEF2 translocase accommodation until the very late stages of the process, and shows an intricate network of interactions preventing the slippage of the translational reading frame. We demonstrate how the accuracy of eukaryotic translocation relies on eukaryote-specific elements of the 80S ribosome, eEF2 and tRNAs. Our findings shed light on the mechanism of translation arrest by the anti-fungal eEF2-binding inhibitor, sordarin. We also propose that the sterically constrained environment imposed by diphthamide, a conserved eukaryotic posttranslational modification in eEF2, not only stabilizes correct Watson-Crick codon-anticodon interactions but may also uncover erroneous peptidyl-tRNA, and therefore contribute to higher accuracy of protein synthesis in eukaryotes.