BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Evaluating hydrological alterations and recommending minimum flow release from the Ujjani dam to improve the Bhima River ecosystem health

Numerous anthropogenic activities like the construction of large dams, storages, and barrages changed the watershed characteristics impacting ecosystem health. In this study, the hydrological alterations (HAs) that have occurred in the Bhima River due to the construction of the Ujjani dam were analyzed. The hydraulic analysis is also performed to determine the hydraulic parameter and recommend the lowest flow release from the dam for improving ecosystem health. Fifty-eight years of data starting from the year 1960 to 2018 were gathered at Yadgir station, which is located downstream of the Ujjani dam. The data were divided into pre- and post-construction river flow discharge. To check for the change in the river flow regime for the post-dam construction period, HA was calculated using Flow Health Software (FHS). The results demonstrate that the dam impoundment reduces high flows primarily by storing flood flow for water supply, irrigation, etc. The velocity and depth provided by the environmental design flow for a flow health (FH) score of 0.62 give a very good habitat to fishes. A minimum release of 24.8 m3/s from the dam is recommended. This study will help policymakers mitigate the impacts of degrading ecosystem health of the Bhima River. HIGHLIGHTS The study analyzes hydrological alterations caused by the construction dam, which have disturbed the river flow regime.; A hydraulic study was performed to determine the hydraulic parameter and to recommend the lowest flow release from the dam for habitat context.; Pre- and post-construction river flow discharge data were used to analyse the impact of human activities on ecology of river.

Mycobacterial proteins interacting with PpiA in pull-down assays.

<p>Mycobacterial proteins interacting with PpiA in pull-down assays.</p

<i>Mycobacterium tuberculosis</i> Cyclophilin A Uses Novel Signal Sequence for Secretion and Mimics Eukaryotic Cyclophilins for Interaction with Host Protein Repertoire

<div><p>Cyclophilins are prolyl isomerases with multitude of functions in different cellular processes and pathological conditions. Cyclophilin A (PpiA) of <i>Mycobacterium tuberculosis</i> is secreted during infection in intraphagosomal niche. However, our understanding about the evolutionary origin, secretory mechanism or the interactome of <i>M. tuberculosis</i> PpiA is limited. This study demonstrates through phylogenetic and structural analyses that PpiA has more proximity to human cyclophilins than the prokaryotic counterparts. We report a unique N-terminal sequence (MADCDSVTNSP) present in pathogenic mycobacterial PpiA and absent in non-pathogenic strains. This sequence stretch was shown to be essential for PpiA secretion. The overexpression of full-length PpiA from <i>M. tuberculosis</i> in non-pathogenic <i>Mycobacterium smegmatis</i> resulted in PpiA secretion while truncation of the N-terminal stretch obstructed the secretion. In addition, presence of an ESX pathway substrate motif in <i>M. tuberculosis</i> PpiA suggested possible involvement of Type VII secretion system. Site-directed mutagenesis of key residues in this motif in full-length PpiA also hindered the secretion in <i>M. smegmatis</i>. Bacterial two-hybrid screens with human lung cDNA library as target were utilized to identify interaction partners of PpiA from host repertoire, and a number of substrates with functional representation in iron storage, signal transduction and immune responses were detected. The extensive host interactome coupled with the sequence and structural similarity to human cyclophilins is strongly suggestive of PpiA being deployed by <i>M. tuberculosis</i> as an effector mimic against the host cyclophilins.</p></div

Identification of a novel signal sequence in pathogenic mycobacterial PpiA.

<p><b>Fig. 4A</b>: A phylogram of mycobacterial PpiA type cyclophilins revealed the coalescing of pathogenic mycobacteria (red) into a clade, different than that of non-pathogenic mycobacteria (black). <b>Fig. 4B</b>: Sequence alignment of the N-terminal stretch revealed that the proposed signal sequence present in pathogenic mycobacterial PpiA was either missing or mismatched in non-pathogenic species. <b>Fig. 4C</b>: Sequence logo analysis of the N-terminal stretch of the mycobacterial PpiA type cyclophilins.</p

Demonstration of <i>M. tuberculosis</i> PpiA secretion and localization.

<p>Immunoblotting was performed to show differential secretion pattern of overexpressed full-length, truncated and YD-ESX mutant forms of <i>M. tuberculosis</i> PpiA in the culture filtrates of <i>M. smegmatis</i>. <b>Fig. 5A</b>: Presence of overexpressed full-length, truncated and YD ESX mutant PpiA in the whole cell lysates (CL) of <i>M. smegmatis</i> (left upper panel). Secretion of overexpressed full-length PpiA is evident in <i>M. smegmatis</i> culture filtrate (CF) while the truncated PpiA without the proposed signal sequence and YD ESX mutant PpiA, though expressed, is not secreted (left lower panel). Expression of Ag85 homolog in all culture filtrates as a control for secretion (right upper panel) and expression of GroEl1 as a cell lysis control and (right lower panel). 12% SDS-PAGE was used in all these blots. <b>Fig. 5B</b>: Truncated PpiA and YD-ESX mutant PpiA showed very little amount of secretion even in two-fold culture filtrate concentrate with respect to the full-length PpiA culture filtrate. 16% SDS-PAGE was overrun to distinguish the size difference in these blots. Cell lysate (CL) fractions with two-fold concentrated amount of truncated and YD ESX mutant PpiA, top panel; Equal concentration of all culture filtrates, middle panel; and Culture filtrate fractions with two fold concentrate of truncated and YD ESX mutant PpiA, bottom panel. <b>Fig. 5C</b>: Immunoelectron micrograph showing localization of secreted full-length PpiA overexpressed in <i>M. smegmatis</i> in comparison with pVV16 vector control in <i>M. smegmatis</i>. Arrows indicate the position of PpiA. T.S: Transverse section, L.S: Longitudinal section.</p

Substrates of PpiA identified from mammalian cell lysates.

<p>Substrates of PpiA identified from mammalian cell lysates.</p

Identification of interaction partners of PpiA in human lung cDNA repertoire by BacterioMatch® two-hybrid screens.

<p>Identification of interaction partners of PpiA in human lung cDNA repertoire by BacterioMatch® two-hybrid screens.</p

Structural and immunoinformatics analysis of <i>M. tuberculosis</i> PpiA.

<p><b>Fig. 3A</b>: Structural overlapping of <i>M. tuberculosis</i> PpiA (green) with human PPWD1 (yellow) demonstrated almost complete overlap, (inset showing the loop region). <b>Fig. 3B</b>: Comparative analysis of structural overlapping between <i>M. tuberculosis</i> PpiA (green) with human PPWD1 (yellow) as well as with <i>E. coli</i> PpiA (red), respectively, revealed a poor overlap with the prokaryotic cyclophilin. <b>Fig. 3C</b>: Structural overlapping of <i>M. tuberculosis</i> PpiA (green) and four human cyclophilins (HPPWD1, HPPIAL3, HPPIC, HPPIA) by Chimera program showed almost complete overlap apart from a region of difference (in form of a loop) in <i>M. tuberculosis</i> PpiA. <b>Fig. 3D</b>: Multiple sequence alignment of the human cyclophilins and <i>M. tuberculosis</i> PpiA identified the region of difference ‘AQGTKDYSTQNASGGP’ (inset, black-bordered box). <b>Fig. 3E</b>: Immunoinformatics analysis using ABCpred software identified putative epitopic regions in <i>M. tuberculosis</i> PpiA.</p

Phylogenetic analysis of cyclophilins.

<p>A circular phylogram representation of the cyclophilin sequences collected from various taxa. <i>M. tuberculosis</i> PpiA is grouped with eukaryotic and actinobacterial counterparts quite distinct from the prokaryotic clades of cyclophilins. The colored labels are used as follows: human cyclophilins – green, <i>M. tuberculosis</i> and <i>Mycobacterium leprae</i> PpiA – red, <i>M. tuberculosis</i> and <i>M. leprae</i> PpiB – brown, <i>E. coli</i> cyclophilins – pink and selected gut microbial cyclophilin – dark blue.</p