Storylines of family medicine I: framing family medicine - history, values and perspectives.

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.

MARS: a motif-based autoregressive model for retrosynthesis prediction.

MOTIVATION: 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. AVAILABILITY AND IMPLEMENTATION: All code and data are available at https://github.com/szu-ljh2020/MARS.

Framing fact-checks as a "confirmation" increases engagement with corrections of misinformation: a four-country study.

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.

Study of real-time parameter measurement of ring rolling pieces based on machine vision.

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.

Leader-follower formation control based on non-inertial frames for non-holonomic mobile robots.

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.

Unexpected extra exon skipping in the DYSF gene during restoring the reading frame by CRISPR/Cas9.

The DYSF gene encoding dysferlin protein is one of the largest and has many transcripts. Pathogenic variants in the gene can lead to various types of myopathies, which makes it a good object for studying the events occurring in it during genome editing by the CRISPR/Cas method. In this study, we evaluated the possibility of permanent skipping of exons 3-4, and 26-27 which deletion does not violate the reading frame and allows to eliminate truncated variants within exons. Editing was performed with simultaneous transfection of two sgRNA- and sa/spCas9-containing plasmids on HEK293T cell cultures and healthy donor myoblasts. Skipping of exons 3-4 was performed by destroying the splicing acceptor sites, and exons 26-27 by cuts in the flanking exons with the corresponding deletion in the DNA. Some unexpected results were obtained, when exons 26-27 were skipped, exon 30 was also absent in the transcript, although it is not alternatively spliced and is normally present in all transcripts. This event indicates that DNA changes near splicing sites can affect adjacent exons and the whole gene. However, this fact requires further study.

mRNA reading frame maintenance during eukaryotic ribosome translocation.

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.

Transference: The Matrix of the Frame.

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.

TCP BBR-n: Increased throughput for wireless-AC networks.

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.

The Roles of eIF4G2 in Leaky Scanning and Reinitiation on the Human Dual-Coding POLG mRNA.

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.

Integrating end-to-end learning with deep geometrical potentials for ab initio RNA structure prediction.

RNAs are fundamental in living cells and perform critical functions determined by their tertiary architectures. However, accurate modeling of 3D RNA structure remains a challenging problem. We present a novel method, DRfold, to predict RNA tertiary structures by simultaneous learning of local frame rotations and geometric restraints from experimentally solved RNA structures, where the learned knowledge is converted into a hybrid energy potential to guide RNA structure assembly. The method significantly outperforms previous approaches by >73.3% in TM-score on a sequence-nonredundant dataset containing recently released structures. Detailed analyses showed that the major contribution to the improvements arise from the deep end-to-end learning supervised with the atom coordinates and the composite energy function integrating complementary information from geometry restraints and end-to-end learning models. The open-source DRfold program with fast training protocol allows large-scale application of high-resolution RNA structure modeling and can be further improved with future expansion of RNA structure databases.

DeepSlice: rapid fully automatic registration of mouse brain imaging to a volumetric atlas.

Registration of data to a common frame of reference is an essential step in the analysis and integration of diverse neuroscientific data. To this end, volumetric brain atlases enable histological datasets to be spatially registered and analyzed, yet accurate registration remains expertise-dependent and slow. In order to address this limitation, we have trained a neural network, DeepSlice, to register mouse brain histological images to the Allen Brain Common Coordinate Framework, retaining registration accuracy while improving speed by >1000 fold.

Pro-ecological and conservation activities are not always beneficial to nature: a case study of two lowland streams in Central Europe.

Since 1990 and in particular, after the implementation of the Water Frame Directive, many positive effects of pro-ecological projects are evident; unfortunately, examples of adverse effects have also been observed. This study aims to indicate how some ill-considered actions, called "pro-ecological", may lead to habitat degradation and the disappearance of valuable hydrobiont species. Two watercourses, representing the lowland gravel stream and sandy stream type, were selected for the study. Literature indicated that in the past, these watercourses were characterized by an excellent ecological status and the presence of valuable rheophilic fauna and flora. Environmental parameters were recorded, macroinvertebrates and ichthyofauna were sampled and analyzed, and finally, indexes were calculated. The results were compared with literature data. In the course of studies conducted in 2011-2015, drastic habitat deterioration and extensive changes in the species structure of ichthyofauna and aquatic invertebrates were observed. Changes in the Smolnica stream have been caused by the three retention basins constructed in 2000, along the lower and middle course; while in Kiszewko, however, the factor for habitat deterioration was connected with the excessive expansion of the Eurasian beaver (Castor fiber), which created a beaver pond 20 m in width, with impoundment elevations of up to 2 m.

Nudging accurate scientific communication.

The recent replicability crisis in social and biomedical sciences has highlighted the need for improvement in the honest transmission of scientific content. We present the results of two studies investigating whether nudges and soft social incentives enhance participants' readiness to transmit high-quality scientific news. In two online randomized experiments (Total N = 2425), participants had to imagine that they were science journalists who had to select scientific studies to report in their next article. They had to choose between studies reporting opposite results (for instance, confirming versus not confirming the effect of a treatment) and varying in traditional signs of research credibility (large versus small sample sizes, randomized versus non-randomized designs). In order to steer participants' choices towards or against the trustworthy transmission of science, we used several soft framing nudges and social incentives. Overall, we find that, although participants show a strong preference for studies using high-sample sizes and randomized design, they are biased towards positive results, and express a preference for results in line with previous intuitions (evincing confirmation bias). Our soft framing nudges and social incentives did not help to counteract these biases. On the contrary, the social incentives against honest transmission of scientific content mildly exacerbated the expression of these biases.

Market framing bias and cross-sectional stock returns.

This paper introduces the market framing bias (MFB): a framing effect that affects the return-risk tradeoff under different frameworks of aggregate market losses and profits, which is measured by the absolute difference between betas in the rising and falling markets. The paper finds that the MFB can predict lower future stock return on the cross-section. Specifically, after controlling for various firm-specific characteristics, this predictive power of the FMB declines over time. Furthermore, the predictive power of the FMB is stable in the short term even after controlling for various pricing factors and firm-specific characteristics.

When Ben met Mary: The Letters of Benjamin Thompson, Reichsgraf von Rumford, to Mary Temple, Viscountess Palmerston, 1793-1804.

This paper publishes the sixty-nine surviving very personal letters that Reichsgraf von Rumford wrote to Viscountess Palmerston after they met in Milan in 1793. The letters draw attention to the private domestic spaces of science and the critical importance of the aristocracy in scientific developments, topics that have both received some discussion recently. They were, however, not written with the purpose of providing historical evidence, but as part of a decade-long friendship which the letters trace, revealing, among other things, Rumford's other amours. They also describe in some detail his thoughts about his activities as a member of the governing elite in Bavaria, his scientific and engineering researches (especially the writing and publication of his Essays), as well as what he would have termed his philanthropic efforts in Bavaria, Northern Italy, Britain, and Ireland. All this is framed within the context of the Revolutionary and Napoleonic wars that in so many ways, directly and indirectly, affected Palmerston's and Rumford's lives and work.

Optimization design and analysis of mobile pump truck frame using response surface methodology.

In order to realize the lightweight design of mobile pump truck, this paper takes the frame of a certain type of mobile pump truck as the research object. The response surface method is used to carry out lightweight design of the longitudinal beam structure of the frame, and the finite element method is used to establish the finite element model to compare and analyze the optimized and original designs. The results show that the height, width and thickness of the optimized longitudinal beam section are reduced by 10mm, 11mm, and 0.8mm respectively, and the weight of the whole frame is reduced by 35.8kg. Before and after optimization, the displacement and stress changes of the frame are small in four motion situations, which meet the lightweight requirements of optimization design.

Charitable giving: The role of framing and information.

We investigate how different levels of information influence the allocation decisions of donors who are entitled to freely distribute a fixed monetary endowment between themselves and a charitable organization in both giving and taking frames. Participants donate significantly higher amounts, when the decision is described as taking rather than giving. This framing effect becomes smaller if more information about the charity is provided.

Development of adjustable variable stiffness restrainer for bridge subjected to seismic excitation.

This paper presents a numerical and experimental assessment of a developed adjustable variable stiffness restrainer (AVSR) utilized for short span bridges. This restrainer has the ability to demonstrate multi stiffness capacity in different stages of bridge's superstructure movement to mitigate the severe damage of bridge due to an earthquake. The multi-level stiffness behavior of developed AVSR is achieved by using multiple mechanical springs with different lengths and placed in parallel in proposed design. A small prototype of developed AVSR has been fabricated and tested under incremental and cyclic loading in order to assess the restrainer performance and the behavior has been validated using finite element analysis. Thereafter, the constitutive model of AVSR was derived for the proposed restrainer in order to implement it in numerical simulations. Furthermore, a parametric study has been conducted numerically to evaluate the effectiveness of different parameters on the restrainer capacity. Moreover, the efficiency of AVSR application in a single degree of freedom system has been assessed by performing seismic analysis on a frame equipped with AVSR subjected to different seismic excitations using Newmark's method. The experimental and finite element results proved the efficiency of developed variable stiffness device to exhibit adjustable action against imposed loads in three designed stages. Furthermore, the parametric study results revealed that increasing the section area of the spring wire leads to increase the restrainer capacity. In contrast, the restrainer resistance is declined by an increase in the mean spring diameter and number of coils for each spring of AVSR. The time history analysis results also indicated that the frame response in terms of displacement, velocity and acceleration is improved by implementing the AVSR in the considered system.

Framing the fallibility of Computer-Aided Detection aids cancer detection.

Computer-Aided Detection (CAD) has been proposed to help operators search for cancers in mammograms. Previous studies have found that although accurate CAD leads to an improvement in cancer detection, inaccurate CAD leads to an increase in both missed cancers and false alarms. This is known as the over-reliance effect. We investigated whether providing framing statements of CAD fallibility could keep the benefits of CAD while reducing over-reliance. In Experiment 1, participants were told about the benefits or costs of CAD, prior to the experiment. Experiment 2 was similar, except that participants were given a stronger warning and instruction set in relation to the costs of CAD. The results showed that although there was no effect of framing in Experiment 1, a stronger message in Experiment 2 led to a reduction in the over-reliance effect. A similar result was found in Experiment 3 where the target had a lower prevalence. The results show that although the presence of CAD can result in over-reliance on the technology, these effects can be mitigated by framing and instruction sets in relation to CAD fallibility.