2,723 results on '"Hahn, Michael"'
Search Results
2. Evidence of Augustinian 'Ressourcement' in the Franciscan Summa Halensis : The Cases of Contra Faustum and De spiritu et littera
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Hahn, Michael S.
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- 2023
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3. Revised Point-Spread Functions for the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory
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Hofmeister, Stefan, Savin, Daniel Wolf, and Hahn, Michael
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
We present revised point-spread functions (PSFs) for the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). These PSFs provide a robust estimate of the light diffracted by the meshes holding the entrance and focal plane filters and the light that is diffusely scattered over medium- to long-distance by the micro-roughness of the mirrors. We first calibrate the diffracted light using flare images. Our modeling of the diffracted light provides reliable determinations of the mesh parameters and finds that about 24 to 33% of the collected light is diffracted, depending on the AIA channel. Then, we fit for the diffuse scattered light using partially lunar occulted images. We find that the diffuse scattered light can be modeled as a superposition of two power law functions that scatter light over the entire length of the detector. The amount of diffuse scattered light ranges from 10 to 35 %, depending on the AIA channel. In total, AIA diffracts and scatters about 40 to 60 % of the collected light over medium to long distances. When correcting for this, bright image regions increase in intensity by about 30 %, dark image regions decrease in intensity by up to 90 %, and the associated differential emission measure analysis of solar features are affected accordingly. Finally, we compare the image reconstructions using our new PSFs to those using the AIA team PSFs and the PSFs of Poduval et al. (2013). We find that our PSFs outperform the others; our PSFs correct well for the flare diffraction pattern and predict accurately the long-distance scattered light in lunar occultations.
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- 2024
4. A Formal Framework for Understanding Length Generalization in Transformers
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Huang, Xinting, Yang, Andy, Bhattamishra, Satwik, Sarrof, Yash, Krebs, Andreas, Zhou, Hattie, Nakkiran, Preetum, and Hahn, Michael
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Computer Science - Machine Learning - Abstract
A major challenge for transformers is generalizing to sequences longer than those observed during training. While previous works have empirically shown that transformers can either succeed or fail at length generalization depending on the task, theoretical understanding of this phenomenon remains limited. In this work, we introduce a rigorous theoretical framework to analyze length generalization in causal transformers with learnable absolute positional encodings. In particular, we characterize those functions that are identifiable in the limit from sufficiently long inputs with absolute positional encodings under an idealized inference scheme using a norm-based regularizer. This enables us to prove the possibility of length generalization for a rich family of problems. We experimentally validate the theory as a predictor of success and failure of length generalization across a range of algorithmic and formal language tasks. Our theory not only explains a broad set of empirical observations but also opens the way to provably predicting length generalization capabilities in transformers.
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- 2024
5. High-Resolution Laboratory Measurements of M-shell Fe EUV Line Emission using EBIT-I
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Fairchild, Alexander J., Hell, Natalie, Beiersdorfer, Peter, Brown, Gregory V., Eckart, Megan E., Hahn, Michael, and Savin, Daniel W.
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Astrophysics - Solar and Stellar Astrophysics - Abstract
Solar physicists routinely utilize observations of Ar-like Fe IX and Cl-like Fe X emission to study a variety of solar structures. However, unidentified lines exist in the Fe IX and Fe X spectra, greatly impeding the spectroscopic diagnostic potential of these ions. Here, we present measurements using the Lawrence Livermore National Laboratory EBIT-I electron beam ion trap in the wavelength range 238-258 A. These studies enable us to unambiguously identify the charge state associated with each of the observed lines. This wavelength range is of particular interest because it contains the Fe IX density diagnostic line ratio 241.74 A/244.91 A, which is predicted to be one of the best density diagnostics of the solar corona, as well as the Fe X 257.26 A magnetic-field-induced transition. We compare our measurements to the Fe IX and Fe X lines tabulated in CHIANTI v10.0.1, which is used for modeling the solar spectrum. In addition, we have measured previously unidentified Fe X lines that will need to be added to CHIANTI and other spectroscopic databases.
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- 2024
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6. Separations in the Representational Capabilities of Transformers and Recurrent Architectures
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Bhattamishra, Satwik, Hahn, Michael, Blunsom, Phil, and Kanade, Varun
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Computer Science - Machine Learning ,Statistics - Machine Learning - Abstract
Transformer architectures have been widely adopted in foundation models. Due to their high inference costs, there is renewed interest in exploring the potential of efficient recurrent architectures (RNNs). In this paper, we analyze the differences in the representational capabilities of Transformers and RNNs across several tasks of practical relevance, including index lookup, nearest neighbor, recognizing bounded Dyck languages, and string equality. For the tasks considered, our results show separations based on the size of the model required for different architectures. For example, we show that a one-layer Transformer of logarithmic width can perform index lookup, whereas an RNN requires a hidden state of linear size. Conversely, while constant-size RNNs can recognize bounded Dyck languages, we show that one-layer Transformers require a linear size for this task. Furthermore, we show that two-layer Transformers of logarithmic size can perform decision tasks such as string equality or disjointness, whereas both one-layer Transformers and recurrent models require linear size for these tasks. We also show that a log-size two-layer Transformer can implement the nearest neighbor algorithm in its forward pass; on the other hand recurrent models require linear size. Our constructions are based on the existence of $N$ nearly orthogonal vectors in $O(\log N)$ dimensional space and our lower bounds are based on reductions from communication complexity problems. We supplement our theoretical results with experiments that highlight the differences in the performance of these architectures on practical-size sequences., Comment: Preprint
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- 2024
7. Theoretical Limitations of Self-Attention in Neural Sequence Models
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Hahn, Michael
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Computational linguistics. Natural language processing ,P98-98.5 - Abstract
Transformers are emerging as the new workhorse of NLP, showing great success across tasks. Unlike LSTMs, transformers process input sequences entirely through self-attention. Previous work has suggested that the computational capabilities of self-attention to process hierarchical structures are limited. In this work, we mathematically investigate the computational power of self-attention to model formal languages. Across both soft and hard attention, we show strong theoretical limitations of the computational abilities of self-attention, finding that it cannot model periodic finite-state languages, nor hierarchical structure, unless the number of layers or heads increases with input length. These limitations seem surprising given the practical success of self-attention and the prominent role assigned to hierarchical structure in linguistics, suggesting that natural language can be approximated well with models that are too weak for the formal languages typically assumed in theoretical linguistics.
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- 2020
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8. Thomas Aquinas's Presentation of Christ as Teacher
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Hahn, Michael S.
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- 2019
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9. [Untitled]
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Hahn, Michael and Baroni, Marco
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Computational linguistics. Natural language processing ,P98-98.5 - Abstract
Recurrent neural networks (RNNs) have reached striking performance in many natural language processing tasks. This has renewed interest in whether these generic sequence processing devices are inducing genuine linguistic knowledge. Nearly all current analytical studies, however, initialize the RNNs with a vocabulary of known words, and feed them tokenized input during training. We present a multi-lingual study of the linguistic knowledge encoded in RNNs trained as character-level language models, on input data with word boundaries removed. These networks face a tougher and more cognitively realistic task, having to discover any useful linguistic unit from scratch based on input statistics. The results show that our “near tabula rasa” RNNs are mostly able to solve morphological, syntactic and semantic tasks that intuitively presuppose word-level knowledge, and indeed they learned, to some extent, to track word boundaries. Our study opens the door to speculations about the necessity of an explicit, rigid word lexicon in language learning and usage.
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- 2019
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10. The Expressive Capacity of State Space Models: A Formal Language Perspective
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Sarrof, Yash, Veitsman, Yana, and Hahn, Michael
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Computer Science - Computation and Language ,Computer Science - Formal Languages and Automata Theory ,Computer Science - Machine Learning - Abstract
Recently, recurrent models based on linear state space models (SSMs) have shown promising performance in language modeling (LM), competititve with transformers. However, there is little understanding of the in-principle abilities of such models, which could provide useful guidance to the search for better LM architectures. We present a comprehensive theoretical study of the capacity of such SSMs as it compares to that of transformers and traditional RNNs. We find that SSMs and transformers have overlapping but distinct strengths. In star-free state tracking, SSMs implement straightforward and exact solutions to problems that transformers struggle to represent exactly. They can also model bounded hierarchical structure with optimal memory even without simulating a stack. On the other hand, we identify a design choice in current SSMs that limits their expressive power. We discuss implications for SSM and LM research, and verify results empirically on a recent SSM, Mamba.
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- 2024
11. InversionView: A General-Purpose Method for Reading Information from Neural Activations
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Huang, Xinting, Panwar, Madhur, Goyal, Navin, and Hahn, Michael
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Computer Science - Machine Learning ,Computer Science - Artificial Intelligence ,Computer Science - Computation and Language - Abstract
The inner workings of neural networks can be better understood if we can fully decipher the information encoded in neural activations. In this paper, we argue that this information is embodied by the subset of inputs that give rise to similar activations. We propose InversionView, which allows us to practically inspect this subset by sampling from a trained decoder model conditioned on activations. This helps uncover the information content of activation vectors, and facilitates understanding of the algorithms implemented by transformer models. We present four case studies where we investigate models ranging from small transformers to GPT-2. In these studies, we show that InversionView can reveal clear information contained in activations, including basic information about tokens appearing in the context, as well as more complex information, such as the count of certain tokens, their relative positions, and abstract knowledge about the subject. We also provide causally verified circuits to confirm the decoded information., Comment: NeurIPS 2024; ICML 2024 Mechanistic Interpretability Workshop oral
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- 2024
12. Linguistic Structure from a Bottleneck on Sequential Information Processing
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Futrell, Richard and Hahn, Michael
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Computer Science - Computation and Language ,Computer Science - Information Theory - Abstract
Human language is a unique form of communication in the natural world, distinguished by its structured nature. Most fundamentally, it is systematic, meaning that signals can be broken down into component parts that are individually meaningful -- roughly, words -- which are combined in a regular way to form sentences. Furthermore, the way in which these parts are combined maintains a kind of locality: words are usually concatenated together, and they form contiguous phrases, keeping related parts of sentences close to each other. We address the challenge of understanding how these basic properties of language arise from broader principles of efficient communication under information processing constraints. Here we show that natural-language-like systematicity arises in codes that are constrained by predictive information, a measure of the amount of information that must be extracted from the past of a sequence in order to predict its future. In simulations, we show that such codes approximately factorize their source distributions, and then express the resulting factors systematically and locally. Next, in a series of cross-linguistic corpus studies, we show that human languages are structured to have low predictive information at the levels of phonology, morphology, syntax, and semantics. Our result suggests that human language performs a sequential, discrete form of Independent Components Analysis on the statistical distribution over meanings that need to be expressed. It establishes a link between the statistical and algebraic structure of human language, and reinforces the idea that the structure of human language is shaped by communication under cognitive constraints.
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- 2024
13. Why are Sensitive Functions Hard for Transformers?
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Hahn, Michael and Rofin, Mark
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Computer Science - Machine Learning - Abstract
Empirical studies have identified a range of learnability biases and limitations of transformers, such as a persistent difficulty in learning to compute simple formal languages such as PARITY, and a bias towards low-degree functions. However, theoretical understanding remains limited, with existing expressiveness theory either overpredicting or underpredicting realistic learning abilities. We prove that, under the transformer architecture, the loss landscape is constrained by the input-space sensitivity: Transformers whose output is sensitive to many parts of the input string inhabit isolated points in parameter space, leading to a low-sensitivity bias in generalization. We show theoretically and empirically that this theory unifies a broad array of empirical observations about the learning abilities and biases of transformers, such as their generalization bias towards low sensitivity and low degree, and difficulty in length generalization for PARITY. This shows that understanding transformers' inductive biases requires studying not just their in-principle expressivity, but also their loss landscape., Comment: ACL 2024
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- 2024
14. Experimental study of Alfv\'en wave reflection from an Alfv\'en-speed gradient relevant to the solar coronal holes
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Bose, Sayak, TenBarge, Jason M., Carter, Troy, Hahn, Michael, Ji, Hantao, Juno, James, Savin, Daniel Wolf, Tripathi, Shreekrishna, and Vincena, Stephen
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Astrophysics - Solar and Stellar Astrophysics ,Physics - Plasma Physics - Abstract
We report the first experimental detection of a reflected Alfv\'en wave from an Alfv\'en-speed gradient under conditions similar to those in coronal holes. The experiments were conducted in the Large Plasma Device at the University of California, Los Angeles. We present the experimentally measured dependence of the coefficient of reflection versus the wave inhomogeneity parameter, i.e., the ratio of the wave length of the incident wave to the length scale of the gradient. Two-fluid simulations using the Gkeyll code qualitatively agree with and support the experimental findings. Our experimental results support models of wave heating that rely on wave reflection at low heights from a smooth Alfv\'en-speed gradient to drive turbulence.
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- 2024
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15. A brief bout of moderate intensity physical activity improves preadolescent children’s behavioral inhibition but does not change their energy intake
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Kelly, Nichole R., Guidinger, Claire, Swan, Daniel M., Thivel, David, Folger, Austin, Luther, Gabriella M., and Hahn, Michael E.
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- 2024
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16. Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells
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Botta, Gregory P, Chao, Joseph, Ma, Hong, Hahn, Michael, Sierra, Gloria, Jia, Jie, Hendrix, Amanda Y, Fong, Joy V Nolte, Ween, Audrey, Vu, Peter, Miller, Aaron, Choi, Michael, Heyman, Benjamin, Daniels, Gregory A, Kaufman, Dan, Jamieson, Catriona, Li, Zonghai, and Cohen, Ezra
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Transplantation ,Cancer ,Lymphoma ,Vaccine Related ,Clinical Trials and Supportive Activities ,Rare Diseases ,Immunization ,Pediatric Cancer ,Pediatric ,Clinical Research ,Hematology ,Good Health and Well Being ,Humans ,Receptors ,Antigen ,T-Cell ,Stomach Neoplasms ,Quality of Life ,T-Lymphocytes ,Receptors ,Chimeric Antigen ,Pathologic Complete Response ,Antigens ,CD19 ,Leukemia ,Tumor Microenvironment ,Translational Medical Research ,Therapies ,Investigational ,Gastrointestinal Neoplasms ,Oncology and carcinogenesis - Abstract
Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.
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- 2024
17. Information Locality in the Processing of Classifier-Noun Dependencies in Mandarin Chinese
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Hao, Hailin, Yang, Yang, and Hahn, Michael
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Linguistics ,Psychology ,Language understanding ,Predictive Processing ,Semantics ,Syntax ,Computational Modeling ,Large Language Models - Abstract
In this paper, we report three reading time (RT) experiments (one using self-paced reading and two using A-Maze) that tested the cognitive mechanisms underlying the processing of classifier-noun dependencies in Mandarin Chinese (MC). We leveraged prenominal relative clauses and the contrast between general and specific classifiers in MC, which offered a good testing ground for existing theories of sentence processing. Results from the A-Maze experiments showed both locality and expectation effects. More importantly, we observed an interaction between locality and expectation in the way of Information Locality (Futrell, 2019; Futrell, Gibson, & Levy, 2020): Expectation-driven facilitation was highly constrained by locality effects. To capture the results, we implemented a resource-rational Lossy-Context Surprisal model (Hahn et al., 2022) for MC, which successfully replicated the key patterns in the A-Maze experiments.
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- 2024
18. A Cross-Linguistic Pressure for Uniform Information Density in Word Order
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Clark, Thomas Hikaru, Meister, Clara, Pimentel, Tiago, Hahn, Michael, Cotterell, Ryan, Futrell, Richard, and Levy, Roger
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Computer Science - Computation and Language - Abstract
While natural languages differ widely in both canonical word order and word order flexibility, their word orders still follow shared cross-linguistic statistical patterns, often attributed to functional pressures. In the effort to identify these pressures, prior work has compared real and counterfactual word orders. Yet one functional pressure has been overlooked in such investigations: the uniform information density (UID) hypothesis, which holds that information should be spread evenly throughout an utterance. Here, we ask whether a pressure for UID may have influenced word order patterns cross-linguistically. To this end, we use computational models to test whether real orders lead to greater information uniformity than counterfactual orders. In our empirical study of 10 typologically diverse languages, we find that: (i) among SVO languages, real word orders consistently have greater uniformity than reverse word orders, and (ii) only linguistically implausible counterfactual orders consistently exceed the uniformity of real orders. These findings are compatible with a pressure for information uniformity in the development and usage of natural languages.
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- 2023
19. Nanosecond infrared laser (NIRL) for cutting roots of human teeth: thermal effects and quality of cutting edges
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Friedrich, Reinhard E., Kohlrusch, Felix K., Ricken, Thomas, Grimm, Julian, Gosau, Martin, Hahn, Michael, von Kroge, Simon, and Hahn, Jan
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- 2024
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20. A unifying theory explains seemingly contradictory biases in perceptual estimation
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Hahn, Michael and Wei, Xue-Xin
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- 2024
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21. Klimaschonende Glasproduktion durch elektrische Beheizung
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Trinks, Volker and Hahn, Michael
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- 2024
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22. Are Non-thermal Velocities in Active Region Coronal Loops Anisotropic?
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Hahn, Michael, Asgari-Targhi, Mahboubeh, and Savin, Daniel Wolf
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Astrophysics - Solar and Stellar Astrophysics - Abstract
We have measured line widths in active region coronal loops in order to determine whether the non-thermal broadening is anisotropic with respect to the magnetic field direction. These non-thermal velocities are caused by unresolved fluid motions. Our analysis method combines spectroscopic data and a magnetic field extrapolation. We analyzed spectra from the Extreme Ultraviolet Imaging Spectrometer on Hinode. A differential emission measure analysis showed that many spectral lines that are commonly considered to be formed in the active region have a substantial contribution from the background quiet Sun. From these spectra we identified lines whose emission was dominated by the active region loops rather than background sources. Using these lines, we constructed maps of the non-thermal velocity. With data from the Helioseismic Magnetic Imager on the Solar Dynamics Observatory and the Coronal Modeling System nonlinear force-free magnetic field reconstruction code, we traced several of the magnetic field lines through the active region. Comparing the spectroscopic and magnetic data, we looked for correlations of non-thermal velocity with the viewing angle between the line of sight and the magnetic field. We found that non-thermal velocities show a weak anti-correlation with the viewing angle. That is, the tendency is for the non-thermal velocity to be slightly larger in the parallel direction. This parallel broadening may be due to acoustic waves or unresolved parallel flows., Comment: Submitted to the Astrophysical Journal
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- 2023
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23. A Theory of Emergent In-Context Learning as Implicit Structure Induction
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Hahn, Michael and Goyal, Navin
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Computer Science - Computation and Language ,Computer Science - Machine Learning - Abstract
Scaling large language models (LLMs) leads to an emergent capacity to learn in-context from example demonstrations. Despite progress, theoretical understanding of this phenomenon remains limited. We argue that in-context learning relies on recombination of compositional operations found in natural language data. We derive an information-theoretic bound showing how in-context learning abilities arise from generic next-token prediction when the pretraining distribution has sufficient amounts of compositional structure, under linguistically motivated assumptions. A second bound provides a theoretical justification for the empirical success of prompting LLMs to output intermediate steps towards an answer. To validate theoretical predictions, we introduce a controlled setup for inducing in-context learning; unlike previous approaches, it accounts for the compositional nature of language. Trained transformers can perform in-context learning for a range of tasks, in a manner consistent with the theoretical results. Mirroring real-world LLMs in a miniature setup, in-context learning emerges when scaling parameters and data, and models perform better when prompted to output intermediate steps. Probing shows that in-context learning is supported by a representation of the input's compositional structure. Taken together, these results provide a step towards theoretical understanding of emergent behavior in large language models.
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- 2023
24. Deriving instrumental point spread functions from partially occulted images
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Hofmeister, Stefan Johann, Hahn, Michael, and Savin, Daniel Wolf
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Solar and Stellar Astrophysics ,Physics - Optics - Abstract
The point-spread function (PSF) of an imaging system describes the response of the system to a point source. Accurately determining the PSF enables one to correct for the combined effects of focussing and scattering within the imaging system, and thereby enhance the spatial resolution and dynamic contrast of the resulting images. We present a semi-empirical semi-blind methodology to derive a PSF from partially occulted images. We partition the two-dimensional PSF into multiple segments, set up a multi-linear system of equations, and directly fit the system of equations to determine the PSF weight in each segment. The algorithm is guaranteed to converge towards the correct instrumental PSF for a large class of occultations, does not require a predefined functional form of the PSF, and can be applied to a large variety of partially occulted images, such as within laboratory settings, regular calibrations within a production line or in the field, astronomical images of distant clusters of stars, or partial solar eclipse images. We show that the central weight of the PSF, which gives the percentage of photons that are not scattered by the instrument, is accurate to bettern than 1.2%. The mean absolute percentage error between the reconstructed and true PSF is usually between 0.5% and 5% for the entire PSF, between 0.5% and 5% for the PSF core, and between 0.5% and 3% for the PSF tail.
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- 2022
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25. Crosslinguistic word order variation reflects evolutionary pressures of dependency and information locality
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Hahn, Michael and Xu, Yang
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Computer Science - Computation and Language - Abstract
Languages vary considerably in syntactic structure. About 40% of the world's languages have subject-verb-object order, and about 40% have subject-object-verb order. Extensive work has sought to explain this word order variation across languages. However, the existing approaches are not able to explain coherently the frequency distribution and evolution of word order in individual languages. We propose that variation in word order reflects different ways of balancing competing pressures of dependency locality and information locality, whereby languages favor placing elements together when they are syntactically related or contextually informative about each other. Using data from 80 languages in 17 language families and phylogenetic modeling, we demonstrate that languages evolve to balance these pressures, such that word order change is accompanied by change in the frequency distribution of the syntactic structures which speakers communicate to maintain overall efficiency. Variability in word order thus reflects different ways in which languages resolve these evolutionary pressures. We identify relevant characteristics that result from this joint optimization, particularly the frequency with which subjects and objects are expressed together for the same verb. Our findings suggest that syntactic structure and usage across languages co-adapt to support efficient communication under limited cognitive resources., Comment: Preprint of peer-reviewed paper published in PNAS. Final copyedited version is available at: https://www.pnas.org/doi/10.1073/pnas.2122604119
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- 2022
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26. Botrytis cinerea infection accelerates ripening and cell wall disassembly to promote disease in tomato fruit
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Silva, Christian J, Adaskaveg, Jaclyn A, Mesquida-Pesci, Saskia D, Ortega-Salazar, Isabel B, Pattathil, Sivakumar, Zhang, Lisha, Hahn, Michael G, van Kan, Jan AL, Cantu, Dario, Powell, Ann LT, and Blanco-Ulate, Barbara
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Plant Biology ,Biological Sciences ,Infectious Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Solanum lycopersicum ,Fruit ,Polysaccharides ,Ethylenes ,Botrytis ,Pectins ,Cell Wall ,Agricultural and Veterinary Sciences ,Plant Biology & Botany ,Plant biology - Abstract
Postharvest fungal pathogens benefit from the increased host susceptibility that occurs during fruit ripening. In unripe fruit, pathogens often remain quiescent and unable to cause disease until ripening begins, emerging at this point into destructive necrotrophic lifestyles that quickly result in fruit decay. Here, we demonstrate that one such pathogen, Botrytis cinerea, actively induces ripening processes to facilitate infections and promote disease in tomato (Solanum lycopersicum). Assessments of ripening progression revealed that B. cinerea accelerated external coloration, ethylene production, and softening in unripe fruit, while mRNA sequencing of inoculated unripe fruit confirmed the corresponding upregulation of host genes involved in ripening processes, such as ethylene biosynthesis and cell wall degradation. Furthermore, an enzyme-linked immunosorbent assay (ELISA)-based glycomics technique used to assess fruit cell wall polysaccharides revealed remarkable similarities in the cell wall polysaccharide changes caused by both infections of unripe fruit and ripening of healthy fruit, particularly in the increased accessibility of pectic polysaccharides. Virulence and additional ripening assessment experiments with B. cinerea knockout mutants showed that induction of ripening depends on the ability to infect the host and break down pectin. The B. cinerea double knockout Δbc polygalacturonase1 Δbc polygalacturonase2 lacking two critical pectin degrading enzymes was incapable of emerging from quiescence even long after the fruit had ripened at its own pace, suggesting that the failure to accelerate ripening severely inhibits fungal survival on unripe fruit. These findings demonstrate that active induction of ripening in unripe tomato fruit is an important infection strategy for B. cinerea.
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- 2023
27. Restriction spectrum imaging with elastic image registration for automated evaluation of response to neoadjuvant therapy in breast cancer
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Andreassen, Maren M Sjaastad, Loubrie, Stephane, Tong, Michelle W, Fang, Lauren, Seibert, Tyler M, Wallace, Anne M, Zare, Somaye, Ojeda-Fournier, Haydee, Kuperman, Joshua, Hahn, Michael, Jerome, Neil P, Bathen, Tone F, Rodríguez-Soto, Ana E, Dale, Anders M, and Rakow-Penner, Rebecca
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Biomedical Imaging ,Cancer ,Clinical Research ,Breast Cancer ,Women's Health ,6.1 Pharmaceuticals ,breast cancer ,locally-advanced breast cancer ,neoadjuvant therapy ,magnetic resonance imaging ,breast MRI ,diffusion-weighted imaging ,restriction spectrum imaging ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeDynamic contrast-enhanced MRI (DCE) and apparent diffusion coefficient (ADC) are currently used to evaluate treatment response of breast cancer. The purpose of the current study was to evaluate the three-component Restriction Spectrum Imaging model (RSI3C), a recent diffusion-weighted MRI (DWI)-based tumor classification method, combined with elastic image registration, to automatically monitor breast tumor size throughout neoadjuvant therapy.Experimental designBreast cancer patients (n=27) underwent multi-parametric 3T MRI at four time points during treatment. Elastically-registered DWI images were used to generate an automatic RSI3C response classifier, assessed against manual DCE tumor size measurements and mean ADC values. Predictions of therapy response during treatment and residual tumor post-treatment were assessed using non-pathological complete response (non-pCR) as an endpoint.ResultsTen patients experienced pCR. Prediction of non-pCR using ROC AUC (95% CI) for change in measured tumor size from pre-treatment time point to early-treatment time point was 0.65 (0.38-0.92) for the RSI3C classifier, 0.64 (0.36-0.91) for DCE, and 0.45 (0.16-0.75) for change in mean ADC. Sensitivity for detection of residual disease post-treatment was 0.71 (0.44-0.90) for the RSI3C classifier, compared to 0.88 (0.64-0.99) for DCE and 0.76 (0.50-0.93) for ADC. Specificity was 0.90 (0.56-1.00) for the RSI3C classifier, 0.70 (0.35-0.93) for DCE, and 0.50 (0.19-0.81) for ADC.ConclusionThe automatic RSI3C classifier with elastic image registration suggested prediction of response to treatment after only three weeks, and showed performance comparable to DCE for assessment of residual tumor post-therapy. RSI3C may guide clinical decision-making and enable tailored treatment regimens and cost-efficient evaluation of neoadjuvant therapy of breast cancer.
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- 2023
28. Automated Patient-level Prostate Cancer Detection with Quantitative Diffusion Magnetic Resonance Imaging
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Zhong, Allison Y, Digma, Leonardino A, Hussain, Troy, Feng, Christine H, Conlin, Christopher C, Tye, Karen, Lui, Asona J, Andreassen, Maren MS, Rodríguez-Soto, Ana E, Karunamuni, Roshan, Kuperman, Joshua, Kane, Christopher J, Rakow-Penner, Rebecca, Hahn, Michael E, Dale, Anders M, and Seibert, Tyler M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Bioengineering ,Prostate Cancer ,Biomedical Imaging ,Clinical Research ,Cancer ,Aging ,Urologic Diseases ,4.2 Evaluation of markers and technologies ,Diffusion magnetic resonance ,imaging ,Prostate ,Quantitative magnetic resonance ,Restriction spectrum imaging ,Diffusion magnetic resonance imaging ,Quantitative magnetic resonance imaging ,Urology & Nephrology ,Clinical sciences - Abstract
BackgroundMultiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSIrs).ObjectiveTo evaluate RSIrs for automated patient-level detection of csPCa.Design setting and participantsWe retrospectively studied all patients (n = 151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI.InterventionWe calculated the maximum RSIrs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records.Outcome measurements and statistical analysisWe compared the performance of RSIrs, ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α = 0.05. We also explored whether the combination of PI-RADS and RSIrs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones.Results and limitationsAUC values for ADC, RSIrs, and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSIrs and PI-RADS were each superior to ADC for patient-level detection of csPCa (p
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- 2023
29. A Multicompartmental Diffusion Model for Improved Assessment of Whole-Body Diffusion-weighted Imaging Data and Evaluation of Prostate Cancer Bone Metastases.
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Conlin, Christopher C, Feng, Christine H, Digma, Leonardino A, Rodríguez-Soto, Ana E, Kuperman, Joshua M, Rakow-Penner, Rebecca, Karow, David S, White, Nathan S, Seibert, Tyler M, Hahn, Michael E, and Dale, Anders M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Biomedical Imaging ,Cancer ,Urologic Diseases ,Aging ,Male ,Humans ,Aged ,Prospective Studies ,Bayes Theorem ,Diffusion Magnetic Resonance Imaging ,Magnetic Resonance Imaging ,Prostatic Neoplasms ,Bone Neoplasms ,Bone Metastases ,Diffusion Signal Model ,Diffusion-weighted Imaging ,Restriction Spectrum Imaging ,Whole-Body MRI - Abstract
Purpose To develop a multicompartmental signal model for whole-body diffusion-weighted imaging (DWI) and apply it to study the diffusion properties of normal tissue and metastatic prostate cancer bone lesions in vivo. Materials and Methods This prospective study (ClinicalTrials.gov: NCT03440554) included 139 men with prostate cancer (mean age, 70 years ± 9 [SD]). Multicompartmental models with two to four tissue compartments were fit to DWI data from whole-body scans to determine optimal compartmental diffusion coefficients. Bayesian information criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness of fit. Diffusion coefficients for the optimal model (having lowest BIC) were used to compute compartmental signal-contribution maps. The signal intensity ratio (SIR) of bone lesions to normal-appearing bone was measured on these signal-contribution maps and on conventional DWI scans and compared using paired t tests (α = .05). Two-sample t tests (α = .05) were used to compare compartmental signal fractions between lesions and normal-appearing bone. Results Lowest BIC was observed from the four-compartment model, with optimal compartmental diffusion coefficients of 0, 1.1 × 10-3, 2.8 × 10-3, and >3.0 ×10-2 mm2/sec. Fitting residuals from this model were significantly lower than from conventional apparent diffusion coefficient mapping (P < .001). Bone lesion SIR was significantly higher on signal-contribution maps of model compartments 1 and 2 than on conventional DWI scans (P < .008). The fraction of signal from compartments 2, 3, and 4 was also significantly different between metastatic bone lesions and normal-appearing bone tissue (P ≤ .02). Conclusion The four-compartment model best described whole-body diffusion properties. Compartmental signal contributions from this model can be used to examine prostate cancer bone involvement. Keywords: Whole-Body MRI, Diffusion-weighted Imaging, Restriction Spectrum Imaging, Diffusion Signal Model, Bone Metastases, Prostate Cancer Clinical trial registration no. NCT03440554 Supplemental material is available for this article. © RSNA, 2023 See also commentary by Margolis in this issue.
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- 2023
30. How Do Syntactic Statistics and Semantic Plausibility Modulate Local Coherence Effects
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Hao, Hailin, Hahn, Michael, and Kaiser, Elsi
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Linguistics ,Psychology ,Language Comprehension ,Language understanding ,Computational Modeling ,Quantitative Behavior - Abstract
Local coherence is a phenomenon in human sentence processing whereby word sequences within a sentence incur processing difficulty when they have a plausible reading different from their true syntactic structure as disambiguated by the global context. Prior research (Tabor, Galantucci, & Richardson, 2003) indicates that more plausible substrings incur more processing difficulty than less plausible ones. In the current article, we challenge this view by providing evidence from two experiments which show that local semantic plausibility can actually facilitate processing. We additionally test whether syntactic statistics can modulate local coherence effects, a prediction made by Lossy-Context Surprisal (LCS; Futrell, Levy, & Gibson, 2020; Hahn, Futrell, Levy, & Gibson, 2022). Although we do not find evidence for effects of syntactic statistics, our overall results cannot be fully explained by any existing account of local coherence alone. We discuss implications for theories of sentence processing.
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- 2023
31. V. Christliche Normen und Ausprägungen römischer Kultur
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Hahn, Michael, primary
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- 2024
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32. VI. Spektren von Kontrolle und Überwachung in spätantiken Gemeinden
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Hahn, Michael, primary
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- 2024
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33. II. Laien, Kleriker, Kongregationen: Soziale Interaktion in der Spätantike
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Hahn, Michael, primary
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- 2024
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34. Titelei/Inhaltsverzeichnis
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Hahn, Michael, primary
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- 2024
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35. Zum Buch
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Hahn, Michael, primary
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- 2024
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36. XI. Register
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Hahn, Michael, primary
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- 2024
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37. IX. Quellenausgaben
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Hahn, Michael, primary
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- 2024
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38. III. Verstöße gegen Sexualnormen
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Hahn, Michael, primary
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- 2024
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39. Vorwort
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Hahn, Michael, primary
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- 2024
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40. IV. Verletzung religiöser Grenzen
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Hahn, Michael, primary
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- 2024
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41. I. Zeitalter der Wachsamkeit
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Hahn, Michael, primary
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- 2024
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42. X. Literatur
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Hahn, Michael, primary
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- 2024
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43. VII. Der christliche Argus
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Hahn, Michael, primary
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- 2024
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44. VIII. Abkürzungsverzeichnis
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Hahn, Michael, primary
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- 2024
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45. Evidence for Parameteric Decay Instability in the Lower Solar Atmosphere
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Hahn, Michael, Fu, Xiangrong, and Savin, Daniel Wolf
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Astrophysics - Solar and Stellar Astrophysics ,Physics - Plasma Physics ,Physics - Space Physics - Abstract
We find evidence for the first observation of the parametric decay instability (PDI) in the lower solar atmosphere. Specifically, we find that the power spectrum of density fluctuations near the solar transition region resembles the power spectrum of the velocity fluctuations, but with the frequency axis scaled up by about a factor of two. These results are from an analysis of the Si IV lines observed by the Interface Region Imaging Spectrometer (IRIS) in the transition region of a polar coronal hole. We also find that the density fluctuations have radial velocity of about 75 km/s and that the velocity fluctuations are much faster with an estimated speed of 250 km/s, as is expected for sound waves and Alfv\'en waves, respectively, in the transition region. Theoretical calculations show that this frequency relationship is consistent with those expected from PDI for the plasma conditions of the observed region. These measurements suggest an interaction between sound waves and Alfv\'en waves in the transition region that is evidence for the parametric decay instability., Comment: Submitted to the Astrophysical Journal
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- 2022
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46. Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost
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Zhong, Allison Y., Lui, Asona J., Kuznetsova, Svetlana, Kallis, Karoline, Conlin, Christopher, Do, Deondre D., Domingo, Mariluz Rojo, Manger, Ryan, Hua, Patricia, Karunamuni, Roshan, Kuperman, Joshua, Dale, Anders M., Rakow-Penner, Rebecca, Hahn, Michael E., van der Heide, Uulke A., Ray, Xenia, and Seibert, Tyler M.
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- 2024
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47. A tradeoff between efficiency and robustness in the hippocampal-neocortical memory network during human and rodent sleep
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Hahn, Michael A., Lendner, Janna D., Anwander, Matthias, Slama, Katarina S.J., Knight, Robert T., Lin, Jack J., and Helfrich, Randolph F.
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- 2024
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48. Ability of a multi-segment foot model to measure kinematic differences in cavus, neutrally aligned, asymptomatic planus, and symptomatic planus foot types
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Stone, Amanda, Stender, Christina J., Whittaker, Eric C., Hahn, Michael E., Rohr, Eric, Cowley, Matthew S., Sangeorzan, Bruce J., and Ledoux, William R.
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- 2024
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49. Results of a survey on applied quality standards in non-interventional studies among the members of the German Association of Research-based Pharmaceutical Companies
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Bethke, Thomas D., Ruppert, Thorsten, Hahn, Michael, and Hundt, Ferdinand
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non-interventional studies ,observational studies ,quality assurance ,quality-assurance measures ,Medicine - Abstract
After the regulatory approval has been obtained, epidemiological studies are acknowledged scientific medical research methods for a new drug which provide additional knowledge about routine application of the drug in clinical daily routine. These studies are performed according to the recommendations of both international and national expert associations, the recommendations of the higher federal authorities in Germany and according to the recommendations of the associations of the pharmaceutical industry. Two surveys among the member companies of the Association of Research-based Pharmaceutical Companies investigated the status of the implementation of the recommendations in the years 2008 and 2010 and compared the results with each other. It could be shown that these recommendations were implemented successfully and were fully adhered to during the conduct of non-interventional studies in Germany. The recommendations define a quality standard which justifies a high level of confidence in the validity of the data collected and the results from these investigations.
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- 2010
50. Quality assurance measures in non-interventional studies: Results of a survey among the members of the Association of Research-Based Pharmaceutical Companies
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Ruppert, Thorsten, Henn, Doris, Hecht, Arthur, Bethke, Thomas D., Hahn, Michael, and Hundt, Ferdinand
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Medicine - Abstract
Research into the therapeutic efficacy of a preparation, its safety and tolerability in the human body, as well as its development into a medicinal product is governed by strict legal provisions and regulations such as those stipulated in the German Drug Law (AMG) and the German Ordinance for Good Clinical Practice in Trials on Medicinal Products for Human Use (GCP-V). In the post-marketing setting, when drugs are tested under routine conditions and in large numbers of patients, non-interventional studies (NIS), which include Anwendungsbeobachtungen (AWB) as the most common form in Germany, have shown to be effective instruments for assessing the safety of a medicinal product and for confirming the results obtained in clinical trials regarding the efficacy of the drug. NIS/AWB studies are not subject to the same strict regulations that govern the development of a medicinal product; in fact they follow recommendations such as those issued by the Federal Higher Authorities and the Expert Committee on Good Epidemiological Practice. Further provisions on NIS/AWB are laid down in the “Codex of the Voluntary Self-regulation for the Pharmaceutical Industry” and the “Common point of view of the Associations of the Pharmaceutical Industry on the assessment of criminality in the collaboration between industry, medical institutions and their staff”. In early 2007, the German Association of Research-Based Pharmaceutical Companies (VFA) consolidated the essential elements of these recommendations, supplemented them by new provisions and published the resulting document as „VFA Recommendations for the Improvement of Quality and Transparency of Non-interventional Studies“. Among other initiatives, these recommendations stipulate specific measures for quality assurance in NIS, approximating NIS standards to those applicable to clinical trials. At the same time NIS are being subjected to transparency criteria with regard to the planning, conduct and publication of the results similar to those that have long been required for clinical studies. A survey among VFA members showed that the VFA recommendations were implemented widely and successfully by the companies currently conducting NIS/AWB projects only a few months after the recommendations had been published. The number of newly initiated NIS has slightly dropped; this trend comes with an increased administrative and logistic burden, greater emphasis on medico-scientific questions, and a focus on adequate methodologies for the analysis of NIS/AWB.
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- 2008
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