What makes the lac-pathway switch: identifying the fluctuations that trigger phenotype switching in gene regulatory systems

Multistable gene regulatory systems sustain different levels of gene expression under identical external conditions. Such multistability is used to encode phenotypic states in processes including nutrient uptake and persistence in bacteria, fate selection in viral infection, cell cycle control, and development. Stochastic switching between different phenotypes can occur as the result of random fluctuations in molecular copy numbers of mRNA and proteins arising in transcription, translation, transport, and binding. However, which component of a pathway triggers such a transition is generally not known. By linking single-cell experiments on the lactose-uptake pathway in E. coli to molecular simulations, we devise a general method to pinpoint the particular fluctuation driving phenotype switching and apply this method to the transition between the uninduced and induced states of the lac genes. We find that the transition to the induced state is not caused only by the single event of lac-repressor unbinding, but depends crucially on the time period over which the repressor remains unbound from the lac-operon. We confirm this notion in strains with a high expression level of the repressor (leading to shorter periods over which the lac-operon remains unbound), which show a reduced switching rate. Our techniques apply to multi-stable gene regulatory systems in general and allow to identify the molecular mechanisms behind stochastic transitions in gene regulatory circuits.Comment: Version

VAISHVANARA CHURNA – STANDARDIZATION, EVALUATION AND COMPARATIVE OVERVIEW OF PHARMACOGNOSTIC AND PHARMACEUTICAL PROPERTIES

Vaishvanara Churna is an Ayurvedic polyherbal formulation used traditionally as a Saraka (laxative), Shotaprasamana (anti-inflammatory) and for the treatment of Amavata (Rheumatoid Arthritis), management of Vibandha (Constipation), Udaravedana (abdominal pain), and Hridroga (heart disease). All the ingredients used in Ayurvedic formulations are of natural origin, owing to which the standardization of Ayurvedic formulations is difficult, which is the need of the hour. Vaishvanara Churna is one such Ayurvedic formulation. The Ayurvedic and other traditional systems of medicines are effective in curing several ailments, but the problem with them is they lack in satisfying quality assurance and quality control parameters, which help us recognize the quality of the formulation. Reliable clinical study data is not available, which thereby increases the scope of research in this area of medicine. This article aims at defining standards by comparing different marketed formulations and an in-house formulation for the evaluation of Vaishvanara Churna. Our study basically intends to highlight the variations observed in marketed samples of Ayurveda formulations, using Vaishvanara Churna as an example. It is an unbiased study and have no intentions to claim anyone of the samples is superior to the other. The Churna was evaluated for its pharmacognostic, pharmaceutical and microbial parameters. The results obtained were within the limits prescribed by Ayurvedic Pharmacopoeia

Insuring Smiles: Predicting routine dental coverage using Spark ML

Finding suitable health insurance coverage can be challenging for individuals and small enterprises in the USA. The Health Insurance Exchange Public Use Files (Exchange PUFs) dataset provided by CMS offers valuable information on health and dental policies [1]. In this paper, we leverage machine learning algorithms to predict if a health insurance plan covers routine dental services for adults. By analyzing plan type, region, deductibles, out-of-pocket maximums, and copayments, we employ Logistic Regression, Decision Tree, Random Forest, Gradient Boost, Factorization Model and Support Vector Machine algorithms. Our goal is to provide a clinical strategy for individuals and families to select the most suitable insurance plan based on income and expenses.Comment: 4 pages, 13 figures, 5 table

Subfunctionalization of phytochrome B1/B2 leads to differential auxin and photosynthetic responses

Gene duplication and polyploidization are genetic mechanisms that instantly add genetic material to an organism\u27s genome. Subsequent modification of the duplicated material leads to the evolution of neofunctionalization (new genetic functions), subfunctionalization (differential retention of genetic functions), redundancy, or a decay of duplicated genes to pseudogenes. Phytochromes are light receptors that play a large role in plant development. They are encoded by a small gene family that in tomato is comprised of five members: PHYA, PHYB1, PHYB2, PHYE, and PHYF. The most recent gene duplication within this family was in the ancestral PHYB gene. Using transcriptome profiling, co-expression network analysis, and physiological and molecular experimentation, we show that tomato SlPHYB1 and SlPHYB2 exhibit both common and non-redundant functions. Specifically, PHYB1 appears to be the major integrator of light and auxin responses, such as gravitropism and phototropism, while PHYB1 and PHYB2 regulate aspects of photosynthesis antagonistically to each other, suggesting that the genes have subfunctionalized since their duplication

Vistaar: Diverse Benchmarks and Training Sets for Indian Language ASR

Improving ASR systems is necessary to make new LLM-based use-cases accessible to people across the globe. In this paper, we focus on Indian languages, and make the case that diverse benchmarks are required to evaluate and improve ASR systems for Indian languages. To address this, we collate Vistaar as a set of 59 benchmarks across various language and domain combinations, on which we evaluate 3 publicly available ASR systems and 2 commercial systems. We also train IndicWhisper models by fine-tuning the Whisper models on publicly available training datasets across 12 Indian languages totalling to 10.7K hours. We show that IndicWhisper significantly improves on considered ASR systems on the Vistaar benchmark. Indeed, IndicWhisper has the lowest WER in 39 out of the 59 benchmarks, with an average reduction of 4.1 WER. We open-source all datasets, code and models.Comment: Accepted in INTERSPEECH 202

CAD for Hepatic Tumor Detection in CT Images

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Phytochrome A Regulates Carbon Flux in Dark Grown Tomato Seedlings

Phytochromes comprise a small family of photoreceptors with which plants gather environmental information that they use to make developmental decisions, from germination to photomorphogenesis to fruit development. Most phytochromes are activated by red light and de-activated by far-red light, but phytochrome A (phyA) is responsive to both and plays an important role during the well-studied transition of seedlings from dark to light growth. The role of phytochromes during skotomorphogenesis (dark development) prior to reaching light, however, has received considerably less attention although previous studies have suggested that phytochrome must play a role even in the dark. We profiled proteomic and transcriptomic seedling responses in tomato during the transition from dark to light growth and found that phyA participates in the regulation of carbon flux through major primary metabolic pathways, such as glycolysis, beta-oxidation, and the tricarboxylic acid (TCA) cycle. Additionally, phyA is involved in the attenuation of root growth soon after reaching light, possibly via control of sucrose allocation throughout the seedling by fine-tuning the expression levels of several sucrose transporters of the SWEET gene family even before the seedling reaches the light. Presumably, by participating in the control of major metabolic pathways, phyA sets the stage for photomorphogenesis for the dark grown seedling in anticipation of light