Miracle-dz/UniFAR-FTUs huggingface dataset:
Continuous lifelong learning for modeling of gene regulation from single cell multiome data by leveraging atlas-scale external data

Accurate context-specific Gene Regulatory Networks (GRNs) inference from genomics data is a crucial task in computational biology. However, existing methods face limitations, such as reliance on gene expression data alone, lower resolution from bulk data, and data scarcity for specific cellular systems. Despite recent technological advancements, including single-cell sequencing and the integration of ATAC-seq and RNA-seq data, learning such complex mechanisms from limited independent data points still presents a daunting challenge, impeding GRN inference accuracy. To overcome this challenge, we present LINGER (LIfelong neural Network for GEne Regulation), a novel deep learning-based method to infer GRNs from single-cell multiome data with paired gene expression and chromatin accessibility data from the same cell. LINGER incorporates both 1) atlas-scale external bulk data across diverse cellular contexts and 2) the knowledge of transcription factor (TF) motif matching to cis-regulatory elements as a manifold regularization to address the challenge of limited data and extensive parameter space in GRN inference. Our results demonstrate that LINGER achieves 2-3 fold higher accuracy over existing methods. LINGER reveals a complex regulatory landscape of genome-wide association studies, enabling enhanced interpretation of disease-associated variants and genes. Additionally, following the GRN inference from a reference sc-multiome data, LINGER allows for the estimation of TF activity solely from bulk or single-cell gene expression data, leveraging the abundance of available gene expression data to identify driver regulators from case-control studies. Overall, LINGER provides a comprehensive tool for robust gene regulation inference from genomics data, empowering deeper insights into cellular mechanisms.
A Phosphoproteomics Data Resource for Systems-level Modeling of Kinase Signaling Networks

Building mechanistic models of kinase-driven signaling pathways requires quantitative measurements of protein phosphorylation across physiologically relevant conditions, but this is rarely done because of the insensitivity of traditional technologies. By using a multiplexed deep phosphoproteome profiling workflow, we were able to generate a deep phosphoproteomics dataset of the EGFR-MAPK pathway in non-transformed MCF10A cells across physiological ligand concentrations with a time resolution of <12 min and in the presence and absence of multiple kinase inhibitors. An improved phosphosite mapping technique allowed us to reliably identify >46,000 phosphorylation sites on >6600 proteins, of which >4500 sites from 2110 proteins displayed a >2-fold increase in phosphorylation in response to EGF. This data was then placed into a cellular context by linking it to 15 previously published protein databases. We found that our results were consistent with much, but not all previously reported data regarding the activation and negative feedback phosphorylation of core EGFR-ERK pathway proteins. We also found that EGFR signaling is biphasic with substrates downstream of RAS/MAPK activation showing a maximum response at <3ng/ml EGF while direct substrates, such as HGS and STAT5B, showing no saturation. We found that RAS activation is mediated by at least 3 parallel pathways, two of which depend on PTPN11. There appears to be an approximately 4-minute delay in pathway activation at the step between RAS and RAF, but subsequent pathway phosphorylation was extremely rapid. Approximately 80 proteins showed a >2-fold increase in phosphorylation across all experiments and these proteins had a significantly higher median number of phosphorylation sites (~18) relative to total cellular phosphoproteins (~4). Over 60% of EGF-stimulated phosphoproteins were downstream of MAPK and included mediators of cellular processes such as gene transcription, transport, signal transduction and cytoskeletal arrangement. Their phosphorylation was either linear with respect to MAPK activation or biphasic, corresponding to the biphasic signaling seen at the level of the EGFR. This deep, integrated phosphoproteomics data resource should be useful in building mechanistic models of EGFR and MAPK signaling and for understanding how downstream responses are regulated.
Liquid–liquid phase separation of α-synuclein is highly sensitive to sequence complexity

The Parkinson’s-associated protein α-synuclein (α-syn) can undergo liquid–liquid phase separation (LLPS), which typically leads to the formation of amyloid fibrils. The coincidence of LLPS and amyloid formation has complicated the identification of the molecular determinants unique to LLPS of α-syn. Moreover, the lack of strategies to selectively perturb LLPS makes it difficult to dissect the biological roles specific to α-syn LLPS, independent of fibrillation. Herein, using a combination of subtle missense mutations, we show that LLPS of α-syn is highly sensitive to its sequence complexity. In fact, we find that even a highly conservative mutation (V16I) that increases sequence complexity without perturbing physicochemical and structural properties, is sufficient to reduce LLPS by 75%; this effect can be reversed by an adjacent V-to-I mutation (V15I) that restores the original sequence complexity. A18T, a complexity-enhancing PD-associated mutation, was likewise found to reduce LLPS, implicating sequence complexity in α-syn pathogenicity. Furthermore, leveraging the differences in LLPS propensities among different α-syn variants, we demonstrate that fibrillation of α-syn does not necessarily correlate with its LLPS. In fact, we identify mutations that selectively perturb LLPS or fibrillation of α-syn, unlike previously studied mutations. The variants and design principles reported herein should therefore empower future studies to disentangle these two phenomena and distinguish their (patho)biological roles.
Tremors in Time: Mechanically Induced Motor Tremors Influence Time Perception

Contemporary research has begun to show a strong relationship between movements and the perception of time. More specifically, concurrent movements serve to both bias and enhance time estimates. To explain these effects, we recently proposed a mechanism by which movements provide a secondary channel for estimating duration that is combined optimally with sensory estimates, in accordance with Bayesian cue combination. However, a critical test of this framework is that by introducing “noise” into movements, sensory estimates of time should similarly become noisier in a manner predicted by cue combination equations. To accomplish this, we had human participants move a robotic arm while estimating intervals of time in either auditory or visual modalities (n=24, ea.). Crucially, we introduced an artificial “tremor” in the arm while subjects were moving, that varied across three levels of amplitude (1-3 N) or frequency (4-12 Hz). The results of both experiments revealed that increasing the frequency of the tremor led to noisier estimates of duration, but in such a way that higher levels of noise saturated the impact, consistent with optimal integration. Further, the effect of noise varied with the base precision of the interval, such that a naturally less precise timing (i.e. visual) was more influenced by the tremor than a naturally more precise modality (i.e. auditory). To explain these findings, we fit the data with a recently developed drift-diffusion model of perceptual decision making, in which the momentary, within-trial variance was allowed to vary across conditions. Here, we found that the model could recapitulate the observed findings, further supporting the theory that movements influence perception directly. Overall, our findings support the proposed framework, and demonstrate the utility of inducing motor noise via artificial tremors, thus providing clinical utility in their connection to movement disorders characterized by tremors.
Methods for decoding cortical gradients of functional connectivity

Macroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a two-segment solution determined by a k-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Finally, we proposed a method for decoding additional components of the gradient decomposition. The current work aims to provide recommendations on best practices and flexible methods for gradient-based functional decoding of fMRI data.
A Programmable Five Qubit Quantum Computer Using Trapped Atomic Ions

Title of dissertation: A Programmable Five Qubit Quantum Computer Using Trapped Atomic Ions Shantanu Debnath, Doctor of Philosophy, 2016 Dissertation directed by: Professor Christopher Monroe Joint Quantum Institute, University of Maryland Department of Physics and National Institute of Standards and Technology Quantum computers can solve certain problems more efficiently compared to conventional classical methods. In the endeavor to build a quantum computer, several competing platforms have emerged that can implement certain quantum algorithms using a few qubits. However, the demonstrations so far have been done usually by tailoring the hardware to meet the requirements of a particular algorithm implemented for a limited number of instances. Although such proof of principal implementations are important to verify the working of algorithms on a physical system, they further need to have the potential to serve as a general purpose quantum computer allowing the flexibility required for running multiple algorithms and be scaled up to host more qubits. Here we demonstrate a small programmable quantum computer based on five trapped atomic ions each of which serves as a qubit. By optically resolving each ion we can individually address them in order to perform a complete set of single-qubit and fully connected two-qubit quantum gates and also perform efficient individual qubit measurements. We implement a computation architecture that accepts an algorithm from a user interface in the form of a standard logic gate sequence and decomposes it into fundamental quantum operations that are native to the hardware using a set of compilation instructions that are defined within the software. These operations are then effected through a pattern of laser pulses that perform coherent rotations on targeted qubits in the chain. The architecture implemented in the experiment therefore gives us unprecedented flexibility in the programming of any quantum algorithm while staying blind to the underlying hardware. As a demonstration we implement the Deutsch-Jozsa and Bernstein-Vazirani algorithms on the five-qubit processor and achieve average success rates of 95 and 90 percent, respectively. We also implement a five-qubit coherent quantum Fourier transform and examine its performance in the period finding and phase estimation protocol. We find fidelities of 84 and 62 percent, respectively. While maintaining the same computation architecture the system can be scaled to more ions using resources that scale favorably (O(N2)) with the number of qubits N . A Programmable Five Qubit Quantum Computer Using Trapped Atomic Ions
Prompt and non-prompt J/ψ production in pp collisionsat √s =7 TeV

The production of J/ψ mesons is studied in pp collisions at √s = 7 TeV with the CMS experiment at the LHC. The measurement is based on a dimuon sample corresponding to an integrated luminosity of 314 nb^(−1). The J/ψ differential cross section is determined, as a function of the J/ψ transverse momentum, in three rapidity ranges. A fit to the decay length distribution is used to separate the prompt from the non-prompt (b hadron to J/ψ) component. Integrated over J/ψ transverse momentum from 6.5 to 30 GeV/c and over rapidity in the range |y|<2.4, the measured cross sections, times the dimuon decay branching fraction, are 70.9±2.1(stat.)±3.0(syst.)±7.8(luminosity) nb for prompt J/ψ mesons assuming unpolarized production and 26.0±1.4(stat.)±1.6(syst.)±2.9(luminosity) nb for J/ψ mesons from b-hadron decays.
Integrable Lattice Models From Gauge Theory

These notes provide an introduction to recent work by Kevin Costello in which integrable lattice models of classical statistical mechanics in two dimensions are understood in terms of quantum gauge theory in four dimensions. This construction will be compared to the more familiar relationship between quantum knot invariants in three dimensions and Chern-Simons gauge theory. (Based on a Whittaker Colloquium at the University of Edinburgh and a lecture at Strings 2016 in Beijing.)
North Atlantic Extratropical Rossby Wave Breaking during the Warm Season: Wave Life Cycle and Role of Diabatic Heating

AbstractThis study investigates the life cycle of anticyclonic Rossby wave breaking during the extended warm season (July–October) over the North Atlantic basin. It was found that upper-tropospheric breaking waves are coupled with lower-level perturbations and can be traced back to a wave train that extends from the North Pacific. The overturning of potential vorticity (PV) contours during wave breaking is associated with the rapid development of an upper-level ridge, which occurs along the east coast of North America and over a warm and moist airstream. The ridge development is investigated using the PV budget analysis and trajectory analysis. The PV budget analysis suggests that the horizontal advection of PV by the perturbed flow dictates the movement and the later decay of the ridge. The ridge amplification, opposed by the horizontal advection of PV, is driven by the vertical advection and the diabatic production of PV, both of which are connected to diabatic heating. The vital role of diabatic heatin.
Pengaruh Model Problem Based Learning dengan Metode Eksperimen dan Diskusi Terhadap Hasil Belajar Fisika Ditinjau dari Sikap Ilmiah Siswa Kelas X MIPA SMA N 1 Mataram

This study aims to determine: (1) the effect of problem based learning models with experimental methods and discussion on learning outcomes; (2) the effect of Scientific Attitude of students towards learning outcomes; (3) the interaction between the model problem based learning with experimental methods and discussion with scientific attitude of students towards learning outcomes. This type of research is an experimental research study design with Factorial Design 2 x 2. Population in research of all X grade student of MIPA at SMA Negeri 1 Mataram academic year 2015/2016. Sampling studies using cluster random sampling, and get class X MIPA 4 as an experimental class I and class X MIPA 7 as experimental class II. The research’s instrument used was a multiple choice test with five alternative answers and considering the validity, reliability, power and the level of difficulty depending matter and using scientific attitude questionnaire instrument. This research showed that the average value of posttest experimental class I was 76.50 and the experimental class II at 79.83 with the average value of the value of the scientific attitude to the experimental class I was 52.42 and 50.70 of the experimental class II. Data obtained beforehand tested normality and homogeneity, earned both classes of normally distributed and homogeneous, then followed by hypothesis testing using analysis of variance (ANOVA) with two different cell. The results of this study show that: (1) There is effect problem based learning model with experimental methods and discussion on learning outcomes; (2) Scientific Attitude effected on the student learning outcomes; (3) There is no interaction between the problem based learning model with experimental methods and discussion with scientific attitude towards learning outcomes.
Analytical Solution of Pantograph Equation with Incommensurate Delay

Abstract: Pantograph equation is a delay differential equation (DDE) arising in electrodynamics. This paper studies the pantograph equation with two delays. The existence, uniqueness, stability and convergence results for DDEs are presented. The series solution of the proposed equation is obtained by using Daftardar-Gejji and Jafari method and given in terms of a special function. This new special function has several properties and relations with other functions. Further, we generalize the proposed equation to fractional-order case and obtain its solution.
Adaptation of the Spalax galili transcriptome to life under hypoxia may hold a key to a complex phenotype including longevity and cancer resistance

The muroid rodent Nannospalax galili (syn. Spalax) is adapted to life in underground burrows and tolerates acute exposure to severe hypoxia. Adaptation to hypoxia is correlated with delayed onset of ageing and resistance against tumour formation. Spalax becomes five to seven times older than its relatives, the mouse and rat, without displaying signs of ageing or developing ageing-related disorders like cancer. Investigating and understanding adapted genes and gene regulatory networks of Spalax might pinpoint novel strategies to maintain an extended healthy phenotype in humans. Here we analysed and compared RNA-Seq data of liver, kidney and spleen of Spalax and rat subjected to 6% O2 or normoxia. We identified differentially expressed genes and pathways common to multiple organs in Spalax and rat. Body-wide differences between Spalax and rat affected biological processes like cell death, defence against reactive oxygen species (ROS), DNA repair, energy metabolism, immune response and angiogenesis, which altogether might play a crucial role in Spalax’s adaptation to life under oxygen deprivation. In all organs, mRNA expression of genes associated with genome stability maintenance and DNA repair was elevated in Spalax compared to rat, accompanied by a lower gene expression of genes associated with aerobic energy metabolism and proinflammatory processes. These transcriptomic changes might be accountable for the extraordinary lifespan of Spalax and its cancer resistance. Our results reveal gene regulatory networks that become candidates for the investigation of the molecular bases that underlie the complex phenotype of Spalax.
Telemedicine Improves Access to Care for Spine Patients With Low Socioeconomic Status

Study Design Retrospective cohort study. Objectives The objective of this study is to compare the likelihood of missing a scheduled telemedicine and in-person appointments for spine patients. The secondary objective is to assess the impact of socioeconomic status on missed telemedicine and in-person appointments. Methods Patients with scheduled outpatient appointments with orthopedic spine faculty between 2019 and 2021 were divided by appointment type: telemedicine (N = 4,387) and in-person (N = 3810). Socioeconomic status was assessed using Area Deprivation Index (ADI) stratified based on percentile: low (<25), medium (25–75), and high (>75) levels of socioeconomic disadvantage. The primary outcome measure was missed clinic appointments, which was defined as having at least one appointment that was cancelled or labeled “no show. ” Results Patients with in-person appointments missed appointments more often than patients with telemedicine visits (51.3% vs 24.7%, P < .001). Patients with high ADI missed their in-person appointments more often than patients with medium and low ADI (59.5% vs 52.2% and 47.5%, P < .001). There was no difference in missed telemedicine visits between patients with high, medium, and low ADI (27.6% vs 24.8% vs 23.8%, P = .294). Patients that missed an appointment were 41.9% more likely to be high ADI (OR 1.42, 95% CI 1.20–1.68, P < .001) and 13.4% more likely to be medium ADI (OR 1.13, 95% CI 1.03–1.26, P = .015) compared with low ADI patients. Conclusions Telemedicine may serve a role in reducing disparity in appointment attendance. While further studies are needed to validate these findings, spine surgeons should consider offering telemedicine as an option to patients.
Nontrivial lower bounds for the $p$-adic valuations of some type of rational numbers

In this paper, we will show that the $p$-adic valuation (where $p$ is a given prime number) of some type of rational numbers is unusually large. This generalizes the very recent results by the author and by A. Dubickas, which are both related to the special case $p = 2$. The crucial point for obtaining our main result is the fact that the $p$-adic valuation of the rational numbers in question is unbounded from above. We will confirm this fact by three different methods; the first two are elementary while the third one leans on the $p$-adic analysis.
Patch tests in patients using immunosuppressants and / or cytokine inhibitors : descriptive analysis of 16 cases

Patch tests are the reference proof for the etiological diagnosis of Allergic Contact Dermatitis (ACD), related to the delayed type 4 hypersensitivity reaction (Gell & Coombs). The use of drugs that interfere with patient immune response, such as corticosteroids, cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and the latest cytokine inhibitors (infliximab, adalimumab), could be considered a limitation to undergo patch tests since they act by inhibiting cell responses. On the other hand, the use of these medications has become increasingly common and, often, their withdrawal is not possible due to the underlying disease. Moreover, studies show that many patients are capable of developing eczematous reactions even when using these drugs. The present study aimed to investigate suspected cases of ACD submitted to patch testing in a non-ideal situation (patients who were receiving immunosuppressive drugs and/or cytokine inhibitors). Data from 16 patients tested between 2009 and 2021 and who were using any of the abovementioned medications at the time of the test were retrospectively analyzed. Different series of allergens were used, the indications of which were based on anamnesis and clinical picture. The tests were applied to the upper back region and removed after 48 hours. The results were obtained after 48 and 96 hours. The possible reactions were: negative, weakly positive (1+) (erythema, infiltration or papules); strongly positive (2+) (edema and/or vesicles); and very strongly positive (3+) (bullae or ulceration). The mean age of the patients was 49 years, consisting of 12 women and four men. The median time of the dermatitis was 37 months (3--180 months). The medications used