gebhart/patrepeval huggingface dataset:
Speech repairs, intonational phrases, and discourse markers: modeling speakers' utterances in spoken dialogue (1999)

Interactive spoken dialogue provides many new challenges for natural language understanding systems. One of the most critical challenges is simply determining the speaker&amp;apos;s intended utter-ances: both segmenting a speaker&amp;apos;s turn into utterances and determining the intended words in each utterance. Even assuming perfect word recognition, the latter problem is complicated by the occurrence of speech repairs, which occur where speakers go back and change (or repeat) something they just said. The words that are replaced or repeated are no longer part of the intended utterance, and so need to be identified. Segmenting turns and resolving repairs are strongly intertwined with a third task: identifying discourse markers. Because of the interactions, and interactions with POS tagging and speech recognition, we need to address these tasks together and early on in the processing stream. This paper presents a statistical language model in which we rede~&amp;apos;ne the speech recognition problem so that it includes the identification of POS tags, discourse markers, speech repairs, and intonational phrases. By solving these simultaneously, we obtain better results on each task than addressing them separately. Our model is able to identify 72 % of turn-internal intonational boundaries with a precision of 71%, 97 % of discourse markers with 96 % precision, and detect and correct 66 % of repairs with 74 % precision.
On the Absorption Cross Section of CdSe Nanocrystal Quantum Dots (2002)

The linear absorption cross section is a crucial parameter to the design of nanocrystal quantum dot devices and to the interpretation of spectroscopic data. We measure and report the size-dependent absorption cross section of CdSe nanocrystal quantum dots. We compare the results for absorption far above the band edge, where the quantum dot density of states may be approximated as a continuum, to simple theoretical models of light scattering from light-absorbing small particles. Excellent agreement with theory is found for dilute dispersions in hexane. We find that for absorption at 350 nm the per particle absorption cross section Cabs (in cm2) for CdSe is Cabs = (5.501 × 105)a3 cm-1, where a is the particle radius in cm. The absorption cross section is observed to be largely insensitive to the solvent refractive index. Detailed modeling of the effect of the ligand shell may be necessary to understand the lack of sensitivity of the absorption properties of nanocrystal quantum dots to the refractive index of the medium.
Effect of microwave irradiation on covalent ligand–DNA interactions (2009)

A 30 second burst of microwave irradiation at an energy level insufficient to cause DNA denaturation or damage drives the covalent reaction between pyrrolobenzodiazepine (PBD) antitumour agents and double-stranded or hairpin oligonucleotides to completion, a process that normally takes between 3-24 hours and thus offering the opportunity for higher-throughput screening of covalent-binding DNA-interactive agents.
The Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Exists as a Preformed Receptor Complex That Can Be Activated by GM-CSF, Interleukin-3, or Interleukin-5 (1997)

The granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor is expressed on normal and malignant hematopoietic cells as well as on cells from other organs in which it transduces a variety of functions. Despite the widespread expression and pleiotropic nature of the GM-CSF receptor, little is known about its assembly and activation mechanism. Using a combination of biochemical and functional approaches, we have found that the human GM-CSF receptor exists as an inducible complex, analogous to the interleukin-3 (IL-3) receptor, and also as a preformed complex, unlike the IL-3 receptor or indeed other members of the cytokine receptor superfamily. We found that monoclonal antibodies to the GM-CSF receptor alpha chain (GMR alpha) and to the common beta chain of the GM-CSF, IL-3, and IL-5 receptors (beta(c)) immunoprecipitated both GMR alpha and beta(c) from the surface of primary myeloid cells, myeloid cell lines, and transfected cells in the absence of GM-CSF. Further association of the two chains could be induced by the addition of GM-CSF. The preformed complex required only the extracellular regions of GMR alpha and beta(c), as shown by the ability of soluble beta(c) to associate with membrane-anchored GMR alpha or soluble GMR alpha. Kinetic experiments on eosinophils and monocytes with radiolabeled GM-CSF, IL-3, and IL-5 showed association characteristics unique to GM-CSF. Significantly, receptor phosphorylation experiments showed that not only GM-CSF but also IL-3 and IL-5 stimulated the phosphorylation of GMR alpha-associated beta(c). These results indicate a pattern of assembly of the heterodimeric GM-CSF receptor that is unique among receptors of the cytokine receptor superfamily. These results also suggest that the preformed GM-CSF receptor complex mediates the instantaneous binding of GM-CSF and is a target of phosphorylation by IL-3 and IL-5, raising the possibility that some of the biologic activities of IL-3 and IL-5 are mediated through the GM-CSF receptor complex.
Stimulatory effect of beta-adrenergic agonists on ileal L cell secretion and modulation by alpha-adrenergic activation (1999)

Postprandial release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L cells results from both nutrient transit in the ileal lumen and neural drive of endocrine cells. The adrenosympathetic system and its effectors have been shown to induce secretion of L cells in vivo or in vitro. Because these transmitters act through three receptors, beta, alpha1, alpha2, coupled to different intracellular pathways, we evaluated the responses of L cells to specific agonists, using the model of isolated vascularly perfused rat ileum. General stimulation of adrenergic receptors with epinephrine (10(-7) M) induced significant GLP-1 and PYY secretions (94+/-38 and 257+/-59 fmol/8 min respectively) which were abolished upon propranolol (10(-7) M) pretreatment and strongly decreased upon infusion with 10(-8) M prazosin. Blockade of alpha2-receptors with idazoxan (10(-8) M) did not alter epinephrine-induced peptide secretion. The beta-adrenergic agonist isoproterenol (10(-6) M) infused for 30 min induced a transient release of GLP-1 and PYY (integrated release over the 8 min of the peak secretion: 38+/-16 and 214+/-69 fmol for GLP-1 and PYY respectively, P<0.05). Because terbutaline but not dobutamine or BRL 37,344 (10(-5) M) induced significant GLP-1 and PYY secretions (135+/-30 and 305+/-39 fmol/8 min respectively), isoproterenol-induced secretions are suggested to result mainly from stimulation of the beta2-isoreceptor type. In contrast, the alpha1-agonist phenylephrine (10(-7) M) did not stimulate peptide release. When co-infused with 10(-6) M or 10(-7) M isoproterenol, 10(-7) M phenylephrine raised GLP-1 release to 174+/-53 and 108+/-28 fmol/8 min respectively (vs 38+/-16 and 35+/-10 fmol/8 min for isoproterenol alone, P<0.05) whereas PYY secretion was not significantly increased. Clonidine (10(-7) M), an alpha2-agonist, induced a moderate and delayed increase of GLP-1 and PYY but abolished the isoproterenol-induced peptide secretion. Our results showed that general stimulation of adrenergic receptors stimulates the secretory activity of ileal endocrine L cells. The net peptide secretion results from the activation of the beta2-isoreceptor type. Additionally, GLP-1 and PYY secretions are positively modulated by alpha1-receptor stimulation and inhibited by alpha2-receptor activation upon beta-receptor occupation.
The analytical validation of the Oncotype DX Recurrence Score assay (2016)

<i>In vitro</i> diagnostic multivariate index assays are highly complex molecular assays that can provide clinically actionable information regarding the underlying tumour biology and facilitate personalised treatment. These assays are only useful in clinical practice if all of the following are established: analytical validation (i.e., how accurately/reliably the assay measures the molecular characteristics), clinical validation (i.e., how consistently/accurately the test detects/predicts the outcomes of interest), and clinical utility (i.e., how likely the test is to significantly improve patient outcomes). In considering the use of these assays, clinicians often focus primarily on the clinical validity/utility; however, the analytical validity of an assay (e.g., its accuracy, reproducibility, and standardisation) should also be evaluated and carefully considered. This review focuses on the rigorous analytical validation and performance of the Oncotype DX<sup>®</sup> Breast Cancer Assay, which is performed at the Central Clinical Reference Laboratory of Genomic Health, Inc. The assay process includes tumour tissue enrichment (if needed), RNA extraction, gene expression quantitation (using a gene panel consisting of 16 cancer genes plus 5 reference genes and quantitative real-time RT-PCR), and an automated computer algorithm to produce a Recurrence Score<sup>®</sup> result (scale: 0-100). This review presents evidence showing that the Recurrence Score result reported for each patient falls within a tight clinically relevant confidence interval. Specifically, the review discusses how the development of the assay was designed to optimise assay performance, presents data supporting its analytical validity, and describes the quality control and assurance programmes that ensure optimal test performance over time.
Semi-Supervised Learning with Deep Generative Models (2014)

The ever-increasing size of modern data sets combined with the difficulty of obtaining label information has made semi-supervised learning one of the problems of significant practical importance in modern data analysis. We revisit the approach to semi-supervised learning with generative models and develop new models that allow for effective generalisation from small labelled data sets to large unlabelled ones. Generative approaches have thus far been either inflexible, inefficient or non-scalable. We show that deep generative models and approximate Bayesian inference exploiting recent advances in variational methods can be used to provide significant improvements, making generative approaches highly competitive for semi-supervised learning.
Circulating DNA in Plasma or Serum (2001)

Small amounts of DNA circulate in both healthy and diseased human plasma/serum, and increased concentrations of DNA are present in the plasma of cancer patients. Characteristics of tumor DNA have been found in genetic material extracted from the plasma of cancer patients. These features include decreased strand stability, the presence of specific oncogene or tumor suppressor gene mutations, microsatellite alterations, Ig rearrangements and hypermethylation of several genes. The results obtained in many different cancers have opened a new research area indicating that plasma DNA might eventually be a suitable target for the development of noninvasive diagnostic, prognostic and follow-up tests for cancer. Following the discovery of tumor derived DNA in plasma or serum, cell-free fetal DNA has also been found in maternal plasma and serum. This discovery provides an easily accessible source of fetal genetic material for prenatal diagnosis.
In Situ Measurements of the Formation and Morphology of Intracellular β-Amyloid Fibrils by Super-Resolution Fluorescence Imaging (2011)

Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Alzheimer's disease (AD). In AD the β-amyloid peptide (Aβ) aggregates to form characteristic fibrillar structures, which are the deposits found as plaques in the brains of patients. We have used direct stochastic optical reconstruction microscopy, dSTORM, to probe the process of in situ Aβ aggregation and the morphology of the ensuing aggregates with a resolution better than 20 nm. We are able to distinguish different types of structures, including oligomeric assemblies and mature fibrils, and observe a number of morphological differences between the species formed in vitro and in vivo, which may be significant in the context of disease. Our data support the recent view that intracellular Aβ could be associated with Aβ pathogenicity in AD, although the major deposits are extracellular, and suggest that this approach will be widely applicable to studies of the molecular mechanisms of protein deposition diseases.
The Reward-Based Eating Drive Scale: A Self-Report Index of Reward-Based Eating (2014)

Why are some individuals more vulnerable to persistent weight gain and obesity than are others? Some obese individuals report factors that drive overeating, including lack of control, lack of satiation, and preoccupation with food, which may stem from reward-related neural circuitry. These are normative and common symptoms and not the sole focus of any existing measures. Many eating scales capture these common behaviors, but are confounded with aspects of dysregulated eating such as binge eating or emotional overeating. Across five studies, we developed items that capture this reward-based eating drive (RED). Study 1 developed the items in lean to obese individuals (n = 327) and examined changes in weight over eight years. In Study 2, the scale was further developed and expert raters evaluated the set of items. Study 3 tested psychometric properties of the final 9 items in 400 participants. Study 4 examined psychometric properties and race invariance (n = 80 women). Study 5 examined psychometric properties and age/gender invariance (n = 381). Results showed that RED scores correlated with BMI and predicted earlier onset of obesity, greater weight fluctuations, and greater overall weight gain over eight years. Expert ratings of RED scale items indicated that the items reflected characteristics of reward-based eating. The RED scale evidenced high internal consistency and invariance across demographic factors. The RED scale, designed to tap vulnerability to reward-based eating behavior, appears to be a useful brief tool for identifying those at higher risk of weight gain over time. Given the heterogeneity of obesity, unique brief profiling of the reward-based aspect of obesity using a self-report instrument such as the RED scale may be critical for customizing effective treatments in the general population.
Pulsed electromagnetic fields stimulation affects osteoclast formation by modulation of osteoprotegerin, RANK ligand and macrophage colony-stimulating factor (2005)

Electromagnetic stimulation has been documented to treat recalcitrant problems of musculoskeletal system. Yet, the underlying mechanisms are not completely understood. In this study, we investigated effect of pulsed electromagnetic fields (PEMF) with parameters modified from clinical bone growth stimulator on osteoclast formation, bone resorption, and cytokines associated with osteoclastogenesis. Marrow cells were harvested from both femora and tibiae of 6 week-old mice and cultured in 8-well chamber slides or 16-well calcium phosphate apatite-coated multitest slides. After 1-day incubation, marrow cells were exposed to PEMF at different electric field intensities for 2 h/day and continued for 9 days. Osteoprotegerin (OPG), receptor activator of NFκB-ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) concentrations of each group were determined after PEMF stimulation. Osteoclast identity was confirmed by both tartrate resistant acid phosphatase (TRAP) stain and bone resorption assay. A statistically significant increase and decrease of osteoclastogenesis and bone resorption areas were found when exposed to PEMF with different intensities. Besides, consistent correlations among OPG, RANKL, M-CSF, osteoclast numbers, and bone resorption after exposure to different intensities of PEMF were observed. These data demonstrated that PEMF with different intensities could regulate osteoclastogenesis, bone resorption, OPG, RANKL, and M-CSF concentrations in marrow culture system.
Molecular amplification in a dynamic combinatorial library using non-covalent interactions (2000)

A trace component within a dynamic combinatorial library of pseudo-peptide hydrazones has been dramatically amplified in a reversible manner through recognition by [18]crown-6.
Arg-Phe-Phe d-Amino Acid Stereochemistry Scan in the Macrocyclic Agouti-Related Protein Antagonist Scaffold c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro] Results in Unanticipated Melanocortin-1 Receptor Agonist Profiles (2018)

The melanocortin-3 and melanocortin-4 receptors (MC3R and MC4R), endogenous agonists derived from the proopiomelanocortin gene transcript, and naturally occurring antagonists agouti and agouti-related protein (AGRP) have been linked to biological pathways associated with energy homeostasis. The active tripeptide sequence of AGRP, Arg111-Phe112-Phe113, is located on a hypothesized β-hairpin loop. Herein, stereochemical modifications of the Arg-Phe-Phe sequence were examined in the octapeptide AGRP-derived macrocyclic scaffold c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was Asn or diaminopropionic acid (Dap). Macrocyclic peptides were synthesized with one, two, or three residues of the Arg-Phe-Phe sequence substituted with the corresponding d-isomer(s), generating a 14 compound library. While l-to-d inversions of the Arg-Phe-Phe sequence in a 20-residue AGRP-derived ligand previously resulted in agonist activity at the MC1R, MC3R, MC4R, and MC5R, only the MC1R was consistently stimulated by the macrocyclic ligands in the present study, with varying ligand potencies and efficacies observed at the MC1R. A general trend of increased MC4R antagonist potency was observed for Dap-containing compounds, while MC5R inverse agonist activity was observed for select ligands. It was observed that stereochemical modification of the Arg-Phe-Phe active tripeptide sequence was insufficient to convert melanocortin antagonist into agonists. Overall, these observations are important in the design of melanocortin ligands possessing potent and selective agonist and antagonist activities.
Characteristics of p-channel Si nano-crystal memory (2001)

In this work, the feasibility of p-channel nano-crystal memory with thin oxide in direct tunneling regime is demonstrated. By comparing the programming characteristics of devices with nano-crystals and devices without nano-crystals, the role of dots as storage node is presented. The programming and erasing mechanisms of p-channel nano-crystal memory were investigated by charge separation technique. For small gate programming voltage, hole tunneling component from inversion layer is dominant. However, valence band electron tunneling component from the valence band in the nano-crystal becomes dominant for large gate voltage. In case of erasing, the electron tunneling occurs from either the conduction band or the valence band. Finally, the comparison of retention between programmed holes and electrons shows that holes have longer retention time.
Origin of Glass Transition of Poly(2-vinylpyridine). A Temperature- and Pressure-Dependent Dielectric Spectroscopy Study (2004)

The dynamics of poly(2-vinylpyridine) (P2VP) have been studied as a function of temperature (in the range from 123 to 453 K), pressure (0.1−270 MPa), and molecular weight (1.1 × 103−3.0 × 104 g/mol), using dielectric spectroscopy (DS) within the frequency range from 10-2 to 106 Hz. Structural methods (wide-angle X-ray scattering) have been employed in parallel with thermodynamic methods (pressure−volume−temperature). Three relaxation processes were found: two above the glass temperature (Tg) associated with the segmental (α-) process and a slower process with an apparent activation volume comparable to the monomer volume and another well below Tg, with an Arrhenius T dependence (β-process). The results from the dynamic study combined with the thermodynamic results revealed that both decreasing thermal energy and insufficient volume lead to glass formation at lower temperatures, with the former having the stronger effect at temperatures near Tg (i.e., values of the ratio of apparent activation energies at constant volume and constant pressure in the range QV/QP ∼ 0.6−0.85 for the different temperatures and pressures investigated).
Characterization of the Structure and Function of a Novel MAP Kinase Kinase (MKK6) (1996)

Mitogen-activated protein (MAP) kinases require dual phosphorylation on threonine and tyrosine residues in order to gain enzymatic activity. This activation is carried out by a family of enzymes known as MAP kinase kinases (MKKs or MEKs). It appears that there are at least four subgroups in this family; MEK1/MEK2 subgroup that activates ERK1/ERK2, MEK5 that activates ERK5/BMK1, MKK3 that activates p38, and MKK4 that activates p38 and Jun kinase. Here we describe the characteristics of a new MKK termed MKK6. The clones we isolated encode two splice isoforms of human MKK6 comprised of 278 and 334 amino acids, respectively, and one murine MKK6 with 237 amino acids. Sequence information derived from cDNA cloning indicated that MKK6 is most closely related to MKK3. The functional data revealed from co-transfection assays suggests that MKK6, like MKK3, selectively phosphorylates p38. Unlike the previously described MKKs (or MEKs), MKK6 exists in a variety of alternatively spliced isoforms with distinct patterns of tissue expression. This suggests novel mechanisms regulating activation and/or function of various forms of MKK6.
Swelling and Loss of Photoreceptors in Chronic Human and Experimental Glaucomas (2000)

<h3>Objective</h3> To determine whether outer retinal changes occur in chronic, presumed primary open-angle glaucoma (POAG). <h3>Methods</h3> The outer retinas from 128 human eyes with a diagnosis of chronic glaucoma (presumably POAG in most cases) and 90 control eyes were examined histologically by 3 masked observers for photoreceptor swelling and loss. Retinas from 9 rhesus monkeys with glaucoma induced experimentally by laser trabecular destruction were compared with 7 fellow (control) eyes. The mean pressure elevations in the eyes with laser trabecular destruction ranged from 26.6 to 53.6 mm Hg with durations varying from 7 to 33 weeks. <h3>Results</h3> Swelling of the red- and green-sensitive cones was observed in a statistically significantly greater proportion of human eyes with presumed POAG compared with the control eyes. Patchy loss of red/green cones and rods was also found in some of the glaucomatous retinas. In a subset of the human eyes with end-stage disease, cone swelling was a variable finding. Although no photoreceptor loss was found in the 9 monkey eyes with experimental glaucoma, 8 had swelling of their red/green cones that was remarkably similar to that seen in the human eyes. Swelling was not present in any of the control monkey eyes. <h3>Conclusions</h3> The photoreceptors are affected by chronically elevated intraocular pressure. <h3>Clinical Relevance</h3> These findings may explain some of the abnormalities of color vision and the electrophysiological effects that have been observed in patients with POAG.
The Synthesis of Substituted Methoxy-Poly(Ethyleneglycol) Derivatives Suitable for Selective Protein Modification (1992)

Abstract The syntheses of methoxypoly(ethyleneglycol) derivatives, functionalized either as hydrazides for the selective attachment of methoxypoly(ethyleneglycol) to carbohydrate domains of glycoproteins, or as iodoacetamides and maleimides for the modification of free sulfhydryl groups, are described.