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Swagatam Mukhopadhyay

Publications and source records attributed to Swagatam Mukhopadhyay.

13 recordsLinked to original sources

Which the Eye Fears: Writing with Read-Blindness Explains Massive Activations in Transformers

Massive activation features (MAs) in Transformers are extreme-value residual-stream features that persist across layers despite the model's ability to suppress them. Why do they survive? Our investigation using an operator-level mechanistic analysis of attention and feed-forward (FFN) blocks reveals that these blocks systematically ignore MA coordinates while reading, but not while writing; creating a read-write asymmetry that blocks corrective feedback while allowing continued accumulation. We find that both attention and feed-forward layers have this read-blindness, and contribute to the emergence and persistence of MAs. To validate prior work that hypothesized that FFN's amplification abilities is the primary reason for MAs (Sun et al., 2026), we analyze the model checkpoints during learning. Contrary to our expectation, read-blindness emerges before FFN amplification, suggesting that it acts upstream in the MA mechanism. We further contribute gradient analysis to link this behavior to surprising asymmetries in the loss landscape, concluding that the model actively maintains this read-blindness. Finally, we find that removing read-blocking at different locations induces compensatory shifts elsewhere, but MAs still persist.

cs.CL↗

Polyformer: a generative framework for thermodynamic modeling of polymeric molecules

The classic paradigm of structural biology is that the sequence of a biomolecule (protein, nucleic acid, lipid, etc) determines its conformation (shape) which determines its biological function. Protein folding programs like AlphaFold address this paradigm by predicting the single best conformation given a sequence that defines the molecule. However, biomolecules are not static structures, and their conformational ensemble determines their function. We present the Polyformer -- a generative framework for thermodynamic modeling of polymeric molecules. Given the sequence and temperature (or another thermodynamic variable), the Polyformer generates conformations faithful to the molecule's thermodynamic conformational ensemble. It is the first generative model that solves three problems simultaneously: how does a molecule fold, what is its conformational ensemble, and how does the conformational ensemble change as we change physical temperature. As a concrete test case, we apply Polyformer to protein domains with 50-111 residues and report good agreement of model predictions to Molecular Dynamics (MD) trajectories.

q-bio.BM↗

Efficient Approximate Methods for Design of Experiments for Copolymer Engineering

We develop a set of algorithms to solve a broad class of Design of Experiment (DoE) problems efficiently. Specifically, we consider problems in which one must choose a subset of polymers to test in experiments such that the learning of the polymeric design rules is optimal. This subset must be selected from a larger set of polymers permissible under arbitrary experimental design constraints. We demonstrate the performance of our algorithms by solving several pragmatic nucleic acid therapeutics engineering scenarios, where limitations in synthesis of chemically diverse nucleic acids or feasibility of measurements in experimental setups appear as constraints. Our approach focuses on identifying optimal experimental designs from a given set of experiments, which is in contrast to traditional, generative DoE methods like BIBD. Finally, we discuss how these algorithms are broadly applicable to well-established optimal DoE criteria like D-optimality.

q-bio.QM↗

Machine Learning 1- and 2-electron reduced density matrices of polymeric molecules

Encoding the electronic structure of molecules using 2-electron reduced density matrices (2RDMs) as opposed to many-body wave functions has been a decades-long quest as the 2RDM contains sufficient information to compute the exact molecular energy but requires only polynomial storage. We focus on linear polymers with varying conformations and numbers of monomers and show that we can use machine learning to predict both the 1-electron and the 2-electron reduced density matrices. Moreover, by applying the Hamiltonian operator to the predicted reduced density matrices we show that we can recover the molecular energy. Thus, we demonstrate the feasibility of a machine learning approach to predicting electronic structure that is generalizable both to new conformations as well as new molecules. At the same time our work circumvents the N-representability problem that has stymied the adaption of 2RDM methods, by directly machine-learning valid Reduced Density Matrices.

physics.chem-ph↗

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.

q-bio.MN↗

What does the Allen Gene Expression Atlas tell us about mouse brain evolution?

We use the Allen Gene Expression Atlas (AGEA) and the OMA ortholog dataset to investigate the evolution of mouse-brain neuroanatomy from the standpoint of the molecular evolution of brain-specific genes. For each such gene, using the phylogenetic tree for all fully sequenced species and the presence of orthologs of the gene in these species, we construct and assign a discrete measure of evolutionary age. The gene expression profile of all gene of similar age, relative to the average gene expression profile, distinguish regions of the brain that are over-represented in the corresponding evolutionary timescale. We argue that the conclusions one can draw on evolution of twelve major brain regions from such a molecular level analysis supplements existing knowledge of mouse brain evolution and introduces new quantitative tools, especially for comparative studies, when AGEA-like data sets for other species become available. Using the functional role of the genes representational of a certain evolutionary timescale and brain region we compare and contrast, wherever possible, our observations with existing knowledge in evolutionary neuroanatomy.

q-bio.QM↗

Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators

Long-distance regulatory interactions between enhancers and their target genes are commonplace in higher eukaryotes. Interposed boundaries or insulators are able to block these long distance regulatory interactions. The mechanistic basis for insulator activity and how it relates to enhancer action-at-a-distance remains unclear. Here we explore the idea that topological loops could simultaneously account for regulatory interactions of distal enhancers and the insulating activity of boundary elements. We show that while loop formation is not in itself sufficient to explain action at a distance, incorporating transient non-specific and moderate attractive interactions between the chromatin fibers strongly enhances long-distance regulatory interactions and is sufficient to generate a euchromatin-like state. Under these same conditions, the subdivision of the loop into two topologically independent loops by insulators inhibits inter-domain interactions. The underlying cause of this effect is a suppression of crossings in the contact map at intermediate distances. Thus our model simultaneously accounts for regulatory interactions at a distance and the insulator activity of boundary elements. This unified model of the regulatory roles of chromatin loops makes several testable predictions that could be confronted with \emph{in vitro} experiments, as well as genomic chromatin conformation capture and fluorescent microscopic approaches.

q-bio.SC↗

Double-Exchange Model: Phase Diagram at Zero-Temperature

The analytical zero-temperature phase diagram of the double exchange model for classical background spins as a function of the carrier density and Hund's coupling in the entire range of these parameters is presented. By constructing a continuum field theory we explore the possibility of a continuous phase transition from ferromagnetic state to a gently varying textured state. We find such a transition in and below two dimensions and show that the emerging stable state is a spin-spiral which survives the tendency towards phase separation into commonly considered phases, and is also energetically favored to the canted state, for low carrier density.

cond-mat.str-el↗

Synthesizing arbitrary two-photon polarization mixed states

Two methods for creating arbitrary two-photon polarization pure states are introduced. Based on these, four schemes for creating two-photon polarization mixed states are proposed and analyzed. The first two schemes can synthesize completely arbitrary two-qubit mixed states, i.e., control all 15 free parameters: Scheme I requires several sets of crystals, while Scheme II requires only a single set, but relies on decohering the pump beam. Additionally, we describe two further schemes which are much easier to implement. Although the total capability of these is still being studied, we show that they can synthesize all two-qubit Werner states, maximally entangled mixed states, Collins-Gisin states, and arbitrary Bell-diagonal states.

quant-ph↗

From Vulcanization to Isotropic and Nematic Rubber Elasticity

A Landau theory is constructed for the vulcanization transition in cross-linked polymer systems with spontaneous nematic ordering. The neo-classical theory of the elasticity of nematic elastomers is derived via the minimization of this Landau free energy; this neo-classical theory contains the classical theory of rubber elasticity as its isotropic limit. Our work not only reveals the statistical-mechanical roots of these elasticity theories, but also demonstrates that they are applicable to a wide class of random solids. It also constitutes a starting-point for the investigation of sample-to-sample fluctuations in various forms of vulcanized matter.

cond-mat.soft↗

Scaling of Entropic Shear Rigidity

The scaling of the shear modulus near the gelation/vulcanization transition is explored heuristically and analytically. It is found that in a dense melt the effective chains of the infinite cluster have sizes that scale sub-linearly with their contour length. Consequently, each contributes k_B T to the rigidity, which leads to a shear modulus exponent dν. In contrast, in phantom elastic networks the scaling is linear in the contour length, yielding an exponent identical to that of the random resistor network conductivity, as predicted by de Gennes'. For non-dense systems, the exponent should cross over to dνwhen the percolation length becomes much larger than the density-fluctuation length.

cond-mat.soft↗

Goldstone-type fluctuations and their implications for the amorphous solid state

In sufficiently high spatial dimensions, the formation of the amorphous (i.e. random) solid state of matter, e.g., upon sufficent crosslinking of a macromolecular fluid, involves particle localization and, concommitantly, the spontaneous breakdown of the (global, continuous) symmetry of translations. Correspondingly, the state supports Goldstone-type low energy, long wave-length fluctuations, the structure and implications of which are identified and explored from the perspective of an appropriate replica field theory. In terms of this replica perspective, the lost symmetry is that of relative translations of the replicas; common translations remain as intact symmetries, reflecting the statistical homogeneity of the amorphous solid state. What emerges is a picture of the Goldstone-type fluctuations of the amorphous solid state as shear deformations of an elastic medium, along with a derivation of the shear modulus and the elastic free energy of the state. The consequences of these fluctuations -- which dominate deep inside the amorphous solid state -- for the order parameter of the amorphous solid state are ascertained and interpreted in terms of their impact on the statistical distribution of localization lengths, a central diagnostic of the the state. The correlations of these order parameter fluctuations are also determined, and are shown to contain information concerning further diagnostics of the amorphous solid state, such as spatial correlations in the statistics of the localization characteristics. Special attention is paid to the properties of the amorphous solid state in two spatial dimensions, for which it is shown that Goldstone-type fluctuations destroy particle localization, the order parameter is driven to zero, and power-law order-parameter correlations hold.

cond-mat.dis-nn↗

Goldstone fluctuations in the amorphous solid state

Goldstone modes in the amorphous solid state, resulting from the spontaneous breaking of translational symmetry due to random localisation of particles, are discussed. Starting from a microscopic model with quenched disorder, the broken symmetry is identified to be that of relative translations of the replicas. Goldstone excitations, corresponding to pure shear deformations, are constructed from long wavelength distortions of the order parameter. The elastic free energy is computed, and it is shown that Goldstone fluctuations destroy localisation in two spatial dimensions, yielding a two-dimensional amorphous solid state characterised by power-law correlations.

cond-mat.soft↗