BiciTaxi

The purpose of this report is to provide an overview of the progress made concerning the development of a solution aimed at the transportation issues faced by residents of Puebla, Mexico, and specifically the community of Colonia Puebla. Colonia Puebla is a low-income community on the outskirts of Puebla. The overall goal is to develop and prototype a product that will alleviate some of the pressure due to the lack of accessibility of transportation and then field test said product in the target community. Ideally, the product would be able to stimulate a micro-economy to provide a source of income to residents. The project consists of an attachment that includes four subsystems, axle, trailer hitch, suspension and frame. The trailer hitch will connect frame to various types of bicycles. The suspension will alleviate bumpiness and axle will hold selected wheels

Inverse problems for nonlinear progressive waves

We propose and study several inverse problems associated with the nonlinear progressive waves that arise in infrasonic inversions. The nonlinear progressive equation (NPE) is of a quasilinear form $\partial_t^2 u=\Delta f(x, u)$ with $f(x, u)=c_1(x) u+c_2(x) u^n$, $n\geq 2$, and can be derived from the hyperbolic system of conservation laws associated with the Euler equations. We establish unique identifiability results in determining $f(x, u)$ as well as the associated initial data by the boundary measurement. Our analysis relies on high-order linearisation and construction of proper Gaussian beam solutions for the underlying wave equations. In addition to its theoretical interest, we connect our study to applications of practical importance in infrasound waveform inversion

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis.

Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available.ImportanceTo fully comprehend the diverse functions of a protein, it is essential to understand the functionality of individual residues. Current methods are highly dependent on evolutionary sequence conservation, which is usually limited by sampling size. Sequence conservation-based methods are further confounded by structural constraints and multifunctionality of proteins. Here we present a method that can systematically identify and annotate functional residues of a given protein. We used a high-throughput functional profiling platform to identify essential residues. Coupling it with homologous-structure comparison, we were able to annotate multiple functions of proteins. We demonstrated the method with the PB1 protein of influenza A virus and identified novel functional residues in addition to its canonical function as an RNA-dependent RNA polymerase. Not limited to virology, this method is generally applicable to other proteins that can be functionally selected and about which homologous-structure information is available

CancerGPT: Few-shot Drug Pair Synergy Prediction using Large Pre-trained Language Models

Large pre-trained language models (LLMs) have been shown to have significant potential in few-shot learning across various fields, even with minimal training data. However, their ability to generalize to unseen tasks in more complex fields, such as biology, has yet to be fully evaluated. LLMs can offer a promising alternative approach for biological inference, particularly in cases where structured data and sample size are limited, by extracting prior knowledge from text corpora. Our proposed few-shot learning approach uses LLMs to predict the synergy of drug pairs in rare tissues that lack structured data and features. Our experiments, which involved seven rare tissues from different cancer types, demonstrated that the LLM-based prediction model achieved significant accuracy with very few or zero samples. Our proposed model, the CancerGPT (with $\sim$ 124M parameters), was even comparable to the larger fine-tuned GPT-3 model (with $\sim$ 175B parameters). Our research is the first to tackle drug pair synergy prediction in rare tissues with limited data. We are also the first to utilize an LLM-based prediction model for biological reaction prediction tasks

PO-084 Research of HIIT Detraining on Mitochondria of Soleus Muscle Beclin1 and Bnip3 Contents in Aging Rats

Objective To observe the temporal variation of Beclin1 and Bnip3 protein in skeletal muscle aging degeneration by constructing the aged rat model, and to observe the effect of HIIT intervention on the changes of Beclin1 and Bnip3 protein and the relationship between the two. It provides a theoretical basis for the effect of exercise on the aging degeneration of skeletal muscle by affecting the level of mitochondrial autophagy. Methods 40 male Wistar rats aged 8 months were randomly divided into quiet control group (C) and HIIT intervention group (H). After the rats entered the animal room for one week of adaptive feeding and exercise, the rats in the C group did not exercise, and the H group exercise alternately based on the maximum oxygen uptake test results of the rats with the 70%-90%-50%VO2max intensity. Once every two weeks, the maximal oxygen uptake of the rats in group H and group C was tested. Group H underwent 50min/ days, 5 days / weeks, and lasted for 16 weeks. The rats in the two groups were randomly selected after the first VO2 test and eighth and sixteenth weeks after intervention. After anesthesia, blood was collected from the abdominal aorta and soleus tissue was obtained. The ROS activity in soleus muscle was tested by fluorescence enzyme labeling method. Isolation of mitochondria from soleus muscle using tissue mitochondria Isolation Kit, and the expression of Beclin1 and Bnip3 in the mitochondria of the soleus muscle was tested by Western blot. The Image Lab 4 software was used to collect the data of the protein test strip, and the SPSS 17 software was used to analyze the data. The results of the data analysis were presented in the form of mean standard deviation. In the process of protein strip analysis, the relative value of the protein content of each sample was obtained by the gray scale analysis method. The results of the first sampling were taken as the baseline value, and the ratio of the H group in the C group of 8 weeks and 16 weeks was obtained with the baseline value, that is, the relative value of the protein content. Then, repeated measurement of variance analysis was used to analyze the differences of different indicators at baseline level, 8 weeks and 12 weeks between group C and group H. The independent sample T test was used without interaction effect, and multivariate analysis of variance was used. A significant level of alpha =0.05 is set. Results (1) the content of ROS in skeletal muscle of rats was related to the process of natural aging (F=119.314, P < 0.001), and the level of ROS would rise with the process of natural collars (F=28.884, P=0.001; F=127.607, P < 0.001) through the comparison of the time points in the group C and the H group. At the same time, the level of ROS in group H was lower than that in group C, but there was no significant difference (P=0.310). And the interaction effect of time and exercise mode (HIIT) will not affect the result (F=0.814, P=0.477). But the growth rate of ROS in group H was lower than that in C group. ⑵Exercise, time change and their interaction did not affect the content of Beclin1 in rat skeletal muscle mitochondria (P > 0.05). ⑶The mitochondrial Bnip3 content in H group and C group was significantly different at 8 weeks (F=14.500, P=0.001), H group was significantly higher than that in C group, but there was no significant difference in mitochondrial Bnip3 content at the 16 week (F=0.090, P=0.767), and the Bnip3 content of skeletal muscle mitochondria changed with age (F=20.852, 0.001). The trend of H increased, but then decreased. There was a linear trend (F=6.950, P=0.005) between the level of mitochondrial Bnip3 content and the intergroup factors (time point changes) and the interaction between time and HIIT movement in rats. Conclusions  With the process of aging, (1) The content of ROS in skeletal muscle of rats increased significantly, while long-term HIIT training could delay the increase, but the best exercise time was unknown. (2) There was no obvious change in Beclin1 content in skeletal muscle mitochondria of rats, and HIIT training had no obvious effect on it. However, the changes in mitochondrial Beclin1 content relative to the total Beclin1 content of skeletal muscle need to be further studied; (3) The content of Bnip3 in skeletal muscle mitochondria in rats is increased, and long-term HIIT training has a delayed effect

Reduced European aerosol emissions suppress winter extremes over northern Eurasia

Winter extreme weather events receive major public attention due to their serious impacts, but the dominant factors regulating their interdecadal trends have not been clearly established. Here, we show that the radiative forcing due to geospatially redistributed anthropogenic aerosols mainly determined the spatial variations of winter extreme weather in the Northern Hemisphere during 1970–2005, a unique transition period for global aerosol forcing. Over this period, the local Rossby wave activity and extreme events (top 10% in wave amplitude) exhibited marked declining trends at high latitudes, mainly in northern Eurasia. The combination of long-term observational data and a state-of-the-art climate model revealed the unambiguous signature of anthropogenic aerosols on the wintertime jet stream, planetary wave activity and surface temperature variability on interdecadal timescales. In particular, warming due to aerosol reductions in Europe enhanced the meridional temperature gradient on the jet’s poleward flank and strengthened the zonal wind, resulting in significant suppression in extreme events over northern Eurasia. These results exemplify how aerosol forcing can impact large-scale extratropical atmospheric dynamics, and illustrate the importance of anthropogenic aerosols and their spatiotemporal variability in assessing the drivers of extreme weather in historical and future climate