Substrate Prediction for RiPP Biosynthetic Enzymes via Masked Language Modeling and Transfer Learning

Ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic enzymes often exhibit promiscuous substrate preferences that cannot be reduced to simple rules. Large language models are promising tools for predicting such peptide fitness landscapes. However, state-of-the-art protein language models are trained on relatively few peptide sequences. A previous study comprehensively profiled the peptide substrate preferences of LazBF (a two-component serine dehydratase) and LazDEF (a three-component azole synthetase) from the lactazole biosynthetic pathway. We demonstrated that masked language modeling of LazBF substrate preferences produced language model embeddings that improved downstream classification models of both LazBF and LazDEF substrates. Similarly, masked language modeling of LazDEF substrate preferences produced embeddings that improved the performance of classification models of both LazBF and LazDEF substrates. Our results suggest that the models learned functional forms that are transferable between distinct enzymatic transformations that act within the same biosynthetic pathway. Our transfer learning method improved performance and data efficiency in data-scarce scenarios. We then fine-tuned models on each data set and showed that the fine-tuned models provided interpretable insight that we anticipate will facilitate the design of substrate libraries that are compatible with desired RiPP biosynthetic pathways

Understanding Cerebellum Granular Layer Network Computations through Mathematical Reconstructions of Evoked Local Field Potentials

Background: The cerebellar granular layer input stage of cerebellum receives information from tactile and sensory re- gions of the body. The somatosensory activity in the cerebellar granular layer corresponds to sensory and tactile input has been observed by recording Local Field Potential (LFP) from the Crus-IIa regions of cerebellum in brain slices and in anesthetized animals. Purpose: In this paper, a detailed biophysical model of Wistar rat cerebellum granular layer net- work model and LFP modelling schemas were used to simulate circuit\u2019s evoked response. Methods: Point Source Ap- proximation and Line Source Approximation were used to reconstruct the network LFP. The LFP mechanism in in vitro was validated in network model and generated the in vivo LFP using the same mechanism. Results: The network simulations distinctly displayed the Trigeminal and Cortical (TC) wave components generated by 2 independent bursts implicating the generation of TC waves by 2 independent granule neuron populations. Induced plasticity was simulated to estimate granule neuron activation related population responses. As a prediction, cerebellar dysfunction (ataxia) was also studied using the model. Dysfunction at individual neurons in the network was affected by the population response. Conclusion: Our present study utilizes available knowledge on known mechanisms in a single cell and associates network function to population responses

Hazard Assessment for Manufacture of Combustible Cartridge Cases using Picrite

A systematic study of the effect of impact, friction, flame and electric spark sensitivity was carried out on the samples combustible cartridge case (CCC) withdrawn at different stages of manufacture. These are Stage I dried felted CCC; stage II-CCC from stage III Coated with nitrocellulose coating. based on the results obtained from various experiments, the CCC can be classified for handling storage and transportation as Group 3, for safety distance category as UN 1.3 and for fire fighting as class 2. further it is concluded from hazard analysis study that the CCCs are safe to handle but these should be protected from naked flame

Doube-pulse Laser-induced Breakdown Spectroscopy of Multi-element Sample Containing Low- And High-Z Analytes

Laser-induced breakdown spectroscopy (LIBS) is a portable, remote, non-invasive analytical technique which effectively distinguishes neutral and ionic species for a range of low- to high-Z elements in a multi-element target. Subsequently, LIBS holds potential in special nuclear material (SNM) sensing and nuclear forensics requiring minimal sample preparation and detecting isotopic shifts which allows for differentiation in SNM (namely U) enrichment levels. Feasible applications include not only nonproliferation and homeland security but also nuclear fuel prospecting and industrial safeguard endorsement. Elements of higher mass with complex atomic structures, such as U, however, result in crowded emission spectra with LIBS, and characteristic emission lines are challenging to discern. Preliminary research suggests double-pulse LIBS (DPLIBS) improves signal sensitivity for analytes of lower atomic mass over conventional single-pulse LIBS (SPLIBS). This study investigates signal sensitivity for low- and high-Z analytes in a glass matrix containing U (1.3%) comparing DPLIBS to SPLIBS. DPLIBS involves sequential firing of 1064 Nd: YAG (FWHM 9 ns) pre-pulse and 10.6 µm TEA CO2 (FWHM 50-100 ns) heating pulse in near collinear geometry; SPLIBS entails only the Nd:YAG laser. Optimization of experimental parameters including inter-pulse delay and energy follows identification of characteristic lines for bulk analytes Ca, Na, and Si and trace analyte U for both DPLIBS and SPLIBS. Temporally-integrated excitation temperature and electron density as well as neutral-to-ionic species ratio constitute relative figures of merit for both DPLIBS and SPLIBS plasma characterization. Temporally-resolved studies provide insight into high-Z U analyte persistence and signal enhancement with DPLIBS as compared to low-Z bulk analytes. The study predicts and discusses optimal emission conditions of U lines and relative figures of merit in both SPLIBS and DPLIBS

The orientation of elliptical galaxies

We determine the orientations of the light distribution of individual elliptical galaxies by combining the profiles of photometric data from the literature with triaxial models. The orientation is given by a Bayesian probability distribution. The likelihood of obtaining the data from a model is a function of the parameters describing the intrinsic shape and the orientation. Integrating the likelihood over the shape parameters, we obtain the estimates of the orientation. We find that the position angle difference between the two suitably chosen points from the profiles of the photometric data plays a key role in constraining the orientation of the galaxy. We apply the methodology to a sample of ten galaxies. The alignment of the intrinsic principle axes of the NGC 3379, 4486 and NGC 5638 are studied.Comment: accepted in Astrophysics and Space Scienc

Diversity and neocolonialism in Big Data research: Avoiding extractivism while struggling with paternalism

The extractive logic of Big Data-driven technology and knowledge production has raised serious concerns. While most criticism initially focused on the impacts on Western societies, attention is now increasingly turning to the consequences for communities in the Global South. To date, debates have focused on private-sector activities. In this article, we start from the conviction that publicly funded knowledge and technology production must also be scrutinized for their potential neocolonial entanglements. To this end, we analyze the dynamics of collaboration in an European Union-funded research project that collects data for developing a social platform focused on diversity. The project includes pilot sites in China, Denmark, the United Kingdom, India, Italy, Mexico, Mongolia, and Paraguay. We present the experience at four field sites and reflect on the project’s initial conception, our collaboration, challenges, progress, and results. We then analyze the different experiences in comparison. We conclude that while we have succeeded in finding viable strategies to avoid contributing to the dynamics of unilateral data extraction as one side of the neocolonial circle, it has been infinitely more difficult to break through the much more subtle but no less powerful mechanisms of paternalism that we find to be prevalent in data-driven North–South relations. These mechanisms, however, can be identified as the other side of the neocolonial circle.</p

Heavy metal concentration in sea water, sediment and bivalves off Tuticorin

Concentration of heavy metals Cd, Cu, Fe, Mn, Ni, Pb and Zn in sea water, sediment and bivalve samples from three stations was studied for one year along Tuticorin coast. The concentration was in the order of Fe>Mn>Zn>Cu>Pb>Cd>Ni. Generally the concentration of Fe was very high in the sediment and bivalves when compared to earlier studies from other areas along the Indian coast. High concentration of Fe, Mn, Cu, Pb and Zn was observed during monsoon season. One way ANOVA indicated statistically significant differences (p<0.01) among the samples in the concentration of Cu, Fe, Mn, Pb and Zn. Except for Cd and Cu, no significant difference was noticed in the seasonal variation of other metals