gebhart/patrepeval huggingface dataset:
Experiment design with applications in identification for control (2004)

The main part of this thesis focuses on optimal experiment design for system identification within the prediction error framework. A rather flexible framework for translating optimal experiment design into tractable convex programs is presented. The design variables are the spectral properties of the external excitations. The framework allows for any linear and finite-dimensional parametrization of the design spectrum or a partial expansion thereof. This includes both continuous and discrete spectra. Constraints on these spectra can be included in the design formulation, either in terms of power bounds or as frequency wise constraints. As quality constraints, general linear functions of the asymptotic covariance matrix of the estimated parameters can be included. Here, different types of frequency-by-frequency constraints on the frequency function estimate are expected to be an important contribution to the area of identification and control. For a certain class of linearly parameterized frequency functions it is possible to derive variance expressions that are exact for finite sample sizes. Based on these variance expressions it is shown that the optimization over the square of the Discrete Fourier Transform (DFT) coefficients of the input leads to convex optimization problems. The optimal input design are compared to the use of standard identification input signals for two benchmark problems. The results show significant benefits of appropriate input designs. Knowledge of the location of non-minimum phase zeros is very useful when designing controllers. Both analytical and numerical results on input design for accurate identification of non-minimum phase zeros are presented. A method is presented for the computation of an upper bound on the maximum over the frequencies of a worst case quality measure, e.g. the worst case performance achieved by a controller in an ellipsoidal uncertainty region. This problem has until now been solved by using a frequency gridding and, here, this is avoided by using the Kalman-Yakubovich-Popov-lemma. The last chapter studies experiment design from the perspective of controller tuning based on experimental data. Iterative Feedback Tuning (IFT) is an algorithm that utilizes sensitivity information from closed-loop experiments for controller tuning. This method is experimentally costly when multivariable systems are considered. Several methods are proposed to reduce the experimental time by approximating the gradient of the cost function. One of these methods uses the same technique of shifting the order of operators as is used in IFT for scalar systems. This method is further analyzed and sufficient conditions for local convergence are derived.
Turning the Light On: Recent Developments in Photoinduced Olefin Metathesis (2017)

Olefin metathesis is one of the most important methods to form carbon–carbon double bonds and has found many applications in industry and academia. The ability to initiate the reaction using external stimulus such as light, with high spatial and temporal resolution is highly advantageous and provides creative novel opportunities in organic syntheses and material sciences. This review article covers recent advances in light-activated olefin metathesis reactions from the development of novel complexes that can be initiated photochemically to recently reported applications of photoinduced olefin metathesis, as well as the bright newly emerging field of photoredox-mediated metal-free ROMP. 1 Introduction 2 Light-Activated Olefin Metathesis Complexes 2.1 Sulfur-Chelated Hoveyda–Grubbs-Type Complexes 2.2 Nitrogen-Chelated Hoveyda–Grubbs-Type Complexes 2.3 Catalyst Activation with Photoacid Generators 2.4 Phototuning of Active Complexes 2.5 Photoactivation of Non-Grubbs-Type Olefin Metathesis Complexes 3 Photoredox-Mediated Metal-Free ROMP 4 Applications of Photoinduced Olefin Metathesis 4.1 Chromatic Orthogonal Olefin Metathesis 4.2 UV-Filter-Assisted Olefin Metathesis 4.3 Photolithographic Olefin Metathesis Polymerization 5 Conclusions
A Foxo/Notch pathway controls myogenic differentiation and fiber type specification (2007)

Forkhead box O (Foxo) transcription factors govern metabolism and cellular differentiation. Unlike Foxo-dependent metabolic pathways and target genes, the mechanisms by which these proteins regulate differentiation have not been explored. Activation of Notch signaling mimics the effects of Foxo gain of function on cellular differentiation. Using muscle differentiation as a model system, we show that Foxo physically and functionally interacts with Notch by promoting corepressor clearance from the Notch effector Csl, leading to activation of Notch target genes. Inhibition of myoblast differentiation by constitutively active Foxo1 is partly rescued by inhibition of Notch signaling while Foxo1 loss of function precludes Notch inhibition of myogenesis and increases myogenic determination gene (MyoD) expression. Accordingly, conditional Foxo1 ablation in skeletal muscle results in increased formation of MyoD-containing (fast-twitch) muscle fibers and altered fiber type distribution at the expense of myogenin-containing (slow-twitch) fibers. Notch/Foxo1 cooperation may integrate environmental cues through Notch with metabolic cues through Foxo1 to regulate progenitor cell maintenance and differentiation.
Evidence-Based Surgical Care and the Evolution of Fast-Track Surgery (2008)

In Brief Background: Optimization of postoperative outcome requires the application of evidence-based principles of care carefully integrated into a multimodal rehabilitation program. Objective: To assess, synthesize, and discuss implementation of “fast-track” recovery programs. Data Sources: Medline MBASE (January 1966–May 2007) and the Cochrane library (January 1966–May 2007) were searched using the following keywords: fast-track, enhanced recovery, accelerated rehabilitation, and multimodal and perioperative care. In addition, the synthesis on the many specific interventions and organizational and implementation issues were based on data published within the past 5 years from major anesthesiological and surgical journals, using systematic reviews where appropriate instead of multiple references of original work. Data Synthesis: Based on an increasing amount of multinational, multicenter cohort studies, randomized studies, and meta-analyses, the concept of the “fast-track methodology” has uniformly provided a major enhancement in recovery leading to decreased hospital stay and with an apparent reduction in medical morbidity but unaltered “surgery-specific” morbidity in a variety of procedures. However, despite being based on a combination of evidence-based unimodal principles of care, recent surveys have demonstrated slow adaptation and implementation of the fast-track methodology. Conclusion: Multimodal evidence-based care within the fast-track methodology significantly enhances postoperative recovery and reduces morbidity, and should therefore be more widely adopted. Further improvement is expected by future integration of minimal invasive surgery, pharmacological stress-reduction, and effective multimodal, nonopioid analgesia. The integration of unimodality evidence-based perioperative care principles into a multimodal “fast-track” rehabilitation program is now well documented to accelerate postoperative recovery and decrease hospital stay. Therefore, this multidisciplinary effort should be more widely adopted.
NOISE CHARACTERIZATION OF PERPENDICULAR MEDIA (1991)

We have applied our precision disk tester and noise measurement procedures to perpendicular media. We look at the randomness of dc media noise from write to write, quantify the deterministic component of this noise, and investigate the head noise and dc track edge noise of perpendicular heads and media. These results are compared with those obtained for longitudinal media. We observe lower correlation coefficients than those for longitudinal media, suggesting that there is more randomness associated with the reversal mechanisms involved in our experiment. We also see that the dc track edge noise is imperceptibly small using our testing operation, implying that double-layered perpendicular dc track edges are of a different form than those of thin film longitudinal single-layered media.
Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells (1998)

Mesenchymal stem cells (MSCs) are a population of pluripotent cells within the bone marrow microenvironment defined by their ability to differentiate into cells of the osteogenic, chondrogenic, tendonogenic, adipogenic, and myogenic lineages. We have developed methodologies to isolate and culture-expand MSCs from human bone marrow, and in this study, we examined the MSC's role as a stromal cell precursor capable of supporting hematopoietic differentiation in vitro. We examined the morphology, phenotype, and in vitro function of cultures of MSCs and traditional marrow-derived stromal cells (MDSCs) from the same marrow sample. MSCs are morphologically distinct from MDSC cultures, and flow cytometric analyses show that MSCs are a homogeneous cell population devoid of hematopoietic cells. RT-PCR analysis of cytokine and growth factor mRNA in MSCs and MDSCs revealed a very similar pattern of mRNAs including IL-6, -7, -8, -11, -12, -14, and -15, M-CSF, Flt-3 ligand, and SCF. Steady-state levels of IL-11 and IL-12 mRNA were found to be greater in MSCs. Addition of IL-1alpha induced steady-state levels of G-CSF and GM-CSF mRNA in both cell preparations. In contrast, IL-1alpha induced IL-1alpha and LIF mRNA levels only in MSCs, further emphasizing phenotypic differences between MSCs and MDSCs. In long-term bone marrow culture (LTBMC), MSCs maintained the hematopoietic differentiation of CD34+ hematopoietic progenitor cells. Together, these data suggest that MSCs represent an important cellular component of the bone marrow microenvironment.
Bilateral filtering for gray and color images (2002)

Bilateral filtering smooths images while preserving edges, by means of a nonlinear combination of nearby image values. The method is noniterative, local, and simple. It combines gray levels or colors based on both their geometric closeness and their photometric similarity, and prefers near values to distant values in both domain and range. In contrast with filters that operate on the three bands of a color image separately, a bilateral filter can enforce the perceptual metric underlying the CIE-Lab color space, and smooth colors and preserve edges in a way that is tuned to human perception. Also, in contrast with standard filtering, bilateral filtering produces no phantom colors along edges in color images, and reduces phantom colors where they appear in the original image.
Dispersion pre‐compensation of 15 femtosecond optical pulses for high‐numerical‐aperture objectives (1998)

The excitation efficiency in two-photon absorption (TPA) microscopy depends strongly - owing to the square dependence of the TPA fluorescence on the excitation intensity - on the temporal width of the excitation pulse. Because of their inherently large frequency bandwidth, ultrashort optical pulses tend to broaden substantially because of dispersion from propagation through the dispersive elements in the microscope. In this paper, the dispersion characteristics of a wide range of microscope objectives are investigated. It is shown that the induced dispersion can be pre-compensated in all cases for pulses as short as 15 fs. Because of the excellent agreement between the results from theoretical modelling and the experimental data, predictions of the possibility of dispersion control for microscope objectives in general, as well as for even shorter pulses, can be inferred. Since for TPA imaging the background due to single photon absorption processes and scattering is independent of the pulse width, proper dispersion pre-compensation - which minimizes the pulse duration at the focal point and hence maximizes the excitation efficiency - provides optimal image contrast in TPA microscopy.
Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. (1991)

Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), which catalyzes formation of gamma-aminobutyric acid from L-glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. Despite the differing GAD isoforms, only one type of GAD cDNA (GAD-1), localized to a syntenic region of chromosome 2, has been isolated from rat, mouse, and cat. Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined.
Deregulation of the Akt Pathway in Human Cancer (2008)

Akt (protein kinase B) is a serine/threonine kinase which is a central regulator of widely divergent cellular processes including proliferation, differentiation, migration, survival and metabolism. Akt is activated by a variety of stimuli, through growth factor receptors, in phosphatidylinositol 3-kinase (PI3K)-dependent manner. Akt is also negatively regulated by the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). A disruption of normal Akt/PKB/PTEN signaling frequently occurs in many human cancers, which plays an important role in cancer development, progression and therapeutic resistance. Numerous studies have revealed the blockage of Akt signaling to result in apoptosis and growth inhibition of tumor cells. Therefore, this signaling pathway, including both upstream and downstream of Akt, has recently attracted considerable attention as a new target for effective cancer therapeutic strategies. In fact, many inhibitors of Akt pathway have been identified and clinical studies of some agents are ongoing. In this review, we describe Akt signaling pathway components and its cellular functions as well as the alterations in human cancers and the therapeutic approaches for targeting the Akt pathway in cancer.
Identification of (R)-(2-Chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyridin-2-yl)-4-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone (JNJ 54166060), a Small Molecule Antagonist of the P2X7 receptor (2016)

The synthesis and SAR of a series of 4,5,6,7-tetrahydro-imidazo[4,5-c]pyridine P2X7 antagonists are described. Addressing P2X7 affinity and liver microsomal stability issues encountered with this template afforded methyl substituted 4,5,6,7-tetrahydro-imidazo[4,5-c]pyridines ultimately leading to the identification of 1 (JNJ 54166060). 1 is a potent P2X7 antagonist with an ED50 = 2.3 mg/kg in rats, high oral bioavailability and low-moderate clearance in preclinical species, acceptable safety margins in rats, and a predicted human dose of 120 mg of QD. Additionally, 1 possesses a unique CYP profile and was found to be a regioselective inhibitor of midazolam CYP3A metabolism.
Restricted / Light Chain Ratio by Flow Cytometry in Germinal Center B Cells in Hashimoto Thyroiditis (2005)

To determine the diagnostic significance of the κ/λ ratio in germinal center (GC) B cells in Hashimoto thyroiditis (HT), we used 4-color flow cytometry to immunophenotype 27 samples (21 patients) of well-characterized HT. B-cell clonality was analyzed further by polymerase chain reaction (PCR) of the immunoglobulin heavy chain (IgH) and bcl-2/IgH fusion genes using DNA extracted from aspirate smears and/or paraffin-embedded tissues. By flow cytometric analysis, the CD10+ GC B cells had a higher mean ± SD κ/λ ratio than the CD10– B cells (5.1 ± 3.3 vs 2.0 ± 0.8; P < .0001, Student t test). In 18 samples (67%), CD10+ GC B cells had a κ/λ ratio greater than 3.07 (the upper limit of κ/λ ratio reported in reactive nodes; range, 3.2-14.4 in the 18 cases). Cases tested by PCR showed no evidence of a clonal proliferation. None of 21 cases developed lymphoma during clinical follow-up of up to 3 years. The κ/λ ratio of CD10+ GC B cells in HT can be skewed markedly beyond that reported in reactive lymph nodes. This finding frequently is present in HT. Pathologists should be familiar with this phenomenon to prevent misdiagnosis of follicular lymphoma in patients with HT.
Agonists for the peroxisome proliferator‐activated receptor‐α and the retinoid X receptor inhibit inflammatory responses of microglia (2005)

The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) plays a key role in lipid metabolism and inflammation. Recently, we demonstrated that administration of the PPAR-alpha agonists gemfibrozil and fenofibrate, inhibit the clinical signs of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). In the present study we investigated the effects of PPAR-alpha agonists on primary mouse microglia, a cell type implicated in the pathology of MS and EAE. Our studies demonstrated that the PPAR-alpha agonists ciprofibrate, fenofibrate, gemfibrozil, and WY 14,643 each inhibited NO production by cytokine-stimulated microglia in a dose-dependent manner. However, fenofibrate and WY 14,643 were more potent inhibitors than gemfibrozil and ciprofibrate. In LPS-stimulated microglia, only fenofibrate and WY 14,643 significantly suppressed NO production. Additionally, PPAR-alpha agonists inhibited the secretion of the proinflammatory cytokines IL-1beta, TNF-alpha, IL-6, and IL-12 p40 and the chemokine MCP-1 by LPS-stimulated microglia. Retinoid X receptors (RXRs) physically interact with PPAR-alpha receptors, and the resulting heterodimers regulate the expression of PPAR-responsive genes. Interestingly, the RXR agonist 9-cis retinoic acid (9-cis RA) inhibited NO production by LPS-stimulated microglia. Furthermore, a combination of 9-cis RA and the PPAR-alpha agonist fenofibrate cooperatively inhibited NO production by these cells. A combination of these agonists also selectively inhibited the expression of proinflammatory cytokines including IL-1beta, TNF-alpha, and IL-6 by LPS-stimulated microglia. Collectively, these results raise the possibility that PPAR-alpha and RXR agonists might have benefit as a therapy in MS, where activated microglia are believed to contribute to disease pathology.
Transgene integration in aspen: structures of integration sites and mechanism of T‐DNA integration (2002)

To obtain insight into the mechanism of transferred DNA (T-DNA) integration in a long-lived tree system, we analysed 30 transgenic aspen lines. In total, 27 right T-DNA/plant junctions, 20 left T-DNA/plant junctions, and 10 target insertions from control plants were obtained. At the right end, the T-DNA was conserved up to the cleavage site in 18 transgenic lines (67%), and the right border repeat was deleted in nine junctions. Nucleotides from the left border repeat were present in 19 transgenic lines out of 20 cases analysed. However, only four (20%) of the left border ends were conserved to the processing end, indicating that the T-DNA left and right ends are treated mechanistically differently during the T-DNA integration process. Comparison of the genomic target sites prior to integration to the T-DNA revealed that the T-DNA inserted into the plant genome without any notable deletion of genomic sequence in three out of 10 transgenic lines analysed. However, deletions of DNA ranging in length from a few nucleotides to more than 500 bp were observed in other transgenic lines. Filler DNAs of up to 235 bp were observed on left and/or right junctions of six transgenic lines, which in most cases originated from the nearby host genomic sequence or from the T-DNA. Short sequence similarities between recombining strands near break points, in particular for the left T-DNA end, were observed in most of the lines analysed. These results confirm the well-accepted T-DNA integration model based on single-stranded annealing followed by ligation of the right border which is preserved by the VirD2 protein. However, a second category of T-DNA integration was also identified in nine transgenic lines, in which the right border of the T-DNA was partly truncated. Such integration events are described via a model for the repair of genomic double-strand breaks in somatic plant cells based on synthesis-dependent strand-annealing. This report in a long-lived tree system provides major insight into the mechanism of transgene integration.
Towards Learning to Converse: Structuring Task-Oriented Human-Human Dialogs (2006)

Data-driven techniques have influenced many aspects of speech and language processing. Models derived from data are generally more robust than hand-crafted systems since they better reflect the distributions of the phenomena being modeled. With the availability of large spoken dialog corpora, dialog management can now reap the benefit of data-driven techniques. In this paper, we present our view of structuring human-human dialogs in order to learn models for human-machine dialogs. We present the problems of dialog segmentation and dialog act labeling, develop a model for predicting and labeling topic segments and dialog acts and evaluate the model on customer-agent dialogs from a catalog service domain
Identification of ZBP-89 as a Novel GATA-1-Associated Transcription Factor Involved in Megakaryocytic and Erythroid Development (2008)

A complete understanding of the transcriptional regulation of developmental lineages requires that all relevant factors be identified. Here, we have taken a proteomic approach to identify novel proteins associated with GATA-1, a lineage-restricted zinc finger transcription factor required for terminal erythroid and megakaryocytic maturation. We identify the Krüppel-type zinc finger transcription factor ZBP-89 as being a component of multiprotein complexes involving GATA-1 and its essential cofactor Friend of GATA-1 (FOG-1). Using chromatin immunoprecipitation assays, we show that GATA-1 and ZBP-89 cooccupy cis-regulatory elements of certain erythroid and megakaryocyte-specific genes, including an enhancer of the GATA-1 gene itself. Loss-of-function studies in zebrafish and mice demonstrate an in vivo requirement for ZBP-89 in megakaryopoiesis and definitive erythropoiesis but not primitive erythropoiesis, phenocopying aspects of FOG-1- and GATA-1-deficient animals. These findings identify ZBP-89 as being a novel transcription factor involved in erythroid and megakaryocytic development and suggest that it serves a cooperative function with GATA-1 and/or FOG-1 in a developmental stage-specific manner.