gebhart/patrepeval huggingface dataset:
Extensibility verification of robust domain selection against out-of-grammar utterances in multi-domain spoken dialogue system (2008)

We developed a robust domain selection method and verified its extensibility. An issue in domain selection is its robustness against out-of-grammar utterances. It is essential to generate correct system responses because such utterances often cause domain selection errors. We therefore integrated the topic estimation results and the dialogue history to construct a robust domain classifier. Another issue is that domain selection should be performed within an extensible framework, because the system is often modified and extended. That is, the classifier should still have high performance without reconstructing it after adding new domains. The extensibility of our method was not experimentally verified yet, because it requires a lot of effort to collect new dialogue data after extending the system. Therefore, we verified extensibility without collecting new data. We constructed the classifier by leaving out some domains in the dialogue data and then evaluated its accuracy as the classifier for the data where the left-out domains were virtually added.
Direct synthesis and characterization of CdS nanobelts (2006)

A method to directly synthesize single crystalline CdS nanobelts has been developed. The advantages of the method in rapid synthesis within several minutes and catalyst free comparing to the previous method propose a potential avenue to the further practical device production and applications. The as-synthesized CdS nanobelts grow along the [100] crystalline direction with usually 500–2000nm in width and about tens to several hundred micrometers in length. Two luminescence peaks around 516 and 758nm in room-temperature photoluminescence spectrum are ascribed to the band-to-band and trap emission, respectively.
Strategy of liver‐directed gene therapy: present status and future prospects (1999)

The liver is particularly amenable to gene therapy as it is the site of many metabolic diseases and malignancies. Thus, liver-directed gene therapy is being actively pursued and developed as a method of treatment for various liver diseases. Strategies of liver-directed gene therapy include drug delivery to the liver, compensation of the defective gene(s), anti-tumor activity, anti-viral therapy, and immunomodulation. The strategy chosen for liver-directed gene therapy depends on the genetic basis of the disease. Many aspects are key factors to the success of the chosen strategy: intervention of genes, efficient gene delivery system, stable transgene expression, transgene regulation, target cell transfection, and timing of transgene expression. Several tactics can be used to overcome problems in the above, and these include the use of a gene switch to exogenously regulate transgene expression, targeting at the transcriptional level, circumvention of the immune response (as in the use of adenovirus vector to achieve long-term correction of genetic diseases), and genetically engineered antibodies in gene transfer. At the present rate of research activity and development, gene therapies may soon be more efficient than current standard treatments for some liver diseases.
Molecular Determinants Underlying the Formation of Stable Intracellular G Protein-coupled Receptor-β-Arrestin Complexes after Receptor Endocytosis* (2001)

beta-Arrestins bind agonist-activated G protein-coupled receptors (GPCRs) and mediate their desensitization and internalization. Although beta-arrestins dissociate from some receptors at the plasma membrane, such as the beta2 adrenergic receptor, they remain associated with other GPCRs and internalize with them into endocytic vesicles. Formation of stable receptor-beta-arrestin complexes that persist inside the cell impedes receptor resensitization, and the aberrant formation of these complexes may play a role in GPCR-based diseases (Barak, L. S., Oakley, R. H., Laporte, S. A., and Caron, M. G. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 93-98). Here, we investigate the molecular determinants responsible for sustained receptor/beta-arrestin interactions. We show in real time and in live human embryonic kidney (HEK-293) cells that a beta-arrestin-2-green fluorescent protein conjugate internalizes into endocytic vesicles with agonist-activated neurotensin-1 receptor, oxytocin receptor, angiotensin II type 1A receptor, and substance P receptor. Using receptor mutagenesis, we demonstrate that the ability of beta-arrestin to remain associated with these receptors is mediated by specific clusters of serine and threonine residues located in the receptor carboxyl-terminal tail. These clusters are remarkably conserved in their position within the carboxyl-terminal domain and serve as primary sites of agonist-dependent receptor phosphorylation. In addition, we identify a beta-arrestin mutant with enhanced affinity for the agonist-activated beta2-adrenergic receptor that traffics into endocytic vesicles with receptors that lack serine/threonine clusters and normally dissociate from wild-type beta-arrestin at the plasma membrane. By identifying receptor and beta-arrestin residues critical for the formation of stable receptor-beta-arrestin complexes, these studies provide novel targets for regulating GPCR responsiveness and treating diseases resulting from abnormal GPCR/beta-arrestin interactions.
Source localization using a current-density minimization approach (2002)

Determining the location of cortical activity from electroencephalographic (EEG) data is important clinically. In this paper, a method is presented which uses the powerful optimization method of simulated annealing in conjunction with a finite-element-based model of the search domain for a single-time slice solution of the EEG-inverse problem. The algorithm highlights a new objective function based on the current-density boundary integral associated with the finite-element formulation as the basis for parameter optimization. In two-dimensional experiments in a shallow tank containing saline, single dipoles are located within 2 mm. Simulations studying the algorithms response to structured noise are also presented. The new objective function is shown to take advantage of the natural framework associated with finite-elements and the results suggest that the approach is capable of resolving dipole locations in simulations and experiments.
Icosahedral RNA Virus Structure (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats (2016)

We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.
Problems with burden-sharing proposal among one billion high emitters (2009)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations (2013)

CoV infections in the elderly are frequent, likely causing substantial medical disease burden.
Characterization of T-Cell Repertoire of the Bone Marrow in Immune-Mediated Aplastic Anemia: Evidence for the Involvement of Antigen-Driven T-Cell Response in Cyclosporine-Dependent Aplastic Anemia (1999)

To determine whether the antigen-driven T-cell response is involved in the pathogenesis of aplastic anemia (AA), we examined the complementarity-determining region 3 (CDR3) size distribution of T-cell receptor (TCR) beta-chain (BV) subfamilies in the bone marrow (BM) of untreated AA patients. AA patients who did not respond to immunosuppressive therapy and those who obtained unmaintained remission early after cyclosporine (CyA) or antithymocyte globulin (ATG) therapy exhibited essentially a normal CDR3 size pattern. In contrast, five patients who needed continuous administration of CyA to maintain remission exhibited a skewed CDR3 size pattern in a number (>40%) of BV subfamilies suggestive of clonal predominance. The skewing of CDR3 size distribution became less pronounced in one of the CyA-dependent patients when the patient achieved unmaintained remission after a 4-year therapy with CyA, whereas it persisted longer than 7 years in the other patient requiring maintenance therapy. Sequencing of BV15 cDNA for which the CDR3 size pattern exhibited apparent clonal predominance in all CyA-dependent patients showed high homology of the amino acid sequence of the CDR3 between two different patients. These findings indicate that antigen-driven expansion of T cells is involved in the pathogenesis of AA characterized by CyA-dependent recovery of hematopoiesis.
Cre-mediated somatic site-specific recombination in mice (1997)

Conditional mutant mice equipped with heterologous recombination systems (Cre/lox or Flp/frt) are promising for studying tissue-specific gene function and for designing better models of human diseases. The utility of these mice depends on the cell target specificity, on the efficiency and on the control over timing of gene (in)activation. We have explored the utility of adenoviral vectors and transgenic mice expressing Cre under the control of tissue-specific promoters to achieve Cre/lox-mediated somatic recombination of the LacZ reporter gene, using a newly generated flox LacZ mouse strain. When adeno Cre viruses were administered via different routes, recombination and expression of LacZ was detected in a wide range of tissues. Whereas in liverbeta-galactosidase activity was quickly lost by turnover of expressing cells, even though the recombined allele was retained,beta-galactosidase in other tissues persisted for many months. Our data indicate that the flox LacZ transgenic line can be utilized effectively to monitor the level and functionality of Cre protein produced upon infection with adeno Cre virus or upon crossbreeding with different Cre transgenic lines.
Transcriptional activation of vascular cell adhesion molecule-1 gene in vivo and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock (1997)

Polymorphonuclear leukocytes (neutrophils) can cause hepatic parenchymal cell injury during endotoxin (ET) shock. Because adhesion molecules are critical for inflammatory cell damage, the role of vascular cell adhesion molecule-1 (VCAM-1) was studied in the pathophysiology of ET shock. ET-sensitive mice (C3Heb/FeJ) were treated with 700 mg/kg galactosamine in combination with 100 microg/kg Salmonella abortus equi ET, 15 microg/kg TNF-alpha, or 13 to 23 microg/kg IL-1. VCAM-1 mRNA formation was strongly activated in animals treated with ET, TNF-alpha, or IL-1. In contrast, only TNF-alpha and IL-1, not ET, induced VCAM-1 gene transcription in livers of ET-resistant mice (C3H/HeJ). Immunohistochemistry and isolation of liver cells during endotoxemia indicated that VCAM-1 mRNA and protein were only formed in endothelial cells and Kupffer cells, not in hepatocytes. Galactosamine/ET induced neutrophil accumulation in sinusoids (515 +/- 30 neutrophils/50 high power fields) followed by transmigration at 7 h. At that time, severe liver injury was observed (necrosis, 53 +/- 5%). An anti-VCAM-1 Ab (3 mg/kg) attenuated the area of necrosis by 60%. The Ab reduced neutrophil transmigration by 84%, but had no effect on the total number of cells in the liver vasculature. Flow cytometric analysis identified the presence of very late Ag-4 on mouse peripheral neutrophils. Our data demonstrated cytokine-dependent VCAM-1 gene transcription and protein expression in the liver during endotoxemia. Neutrophils were able to use very late Ag-4/VCAM-1 interactions to transmigrate into liver parenchyma in vivo. Preventing transmigration by blocking VCAM-1 protected hepatocytes against neutrophil-induced injury.
Learning and Transferring Mid-level Image Representations Using Convolutional Neural Networks (2014)

Convolutional neural networks (CNN) have recently shown outstanding image classification performance in the large- scale visual recognition challenge (ILSVRC2012). The success of CNNs is attributed to their ability to learn rich mid-level image representations as opposed to hand-designed low-level features used in other image classification methods. Learning CNNs, however, amounts to estimating millions of parameters and requires a very large number of annotated image samples. This property currently prevents application of CNNs to problems with limited training data. In this work we show how image representations learned with CNNs on large-scale annotated datasets can be efficiently transferred to other visual recognition tasks with limited amount of training data. We design a method to reuse layers trained on the ImageNet dataset to compute mid-level image representation for images in the PASCAL VOC dataset. We show that despite differences in image statistics and tasks in the two datasets, the transferred representation leads to significantly improved results for object and action classification, outperforming the current state of the art on Pascal VOC 2007 and 2012 datasets. We also show promising results for object and action localization.
A real-time high-resolution optical SAR processor (2010)

An optical SAR processor prototype exhibiting real-time and fine sampling capabilities has been successfully developed and tested. Synthetic Aperture Radar (SAR) images are typically processed digitally applying dedicated Fast Fourier Transform (FFT) algorithms. These operations are time consuming and require a large amount of processing power and are often performed in one dimension at a time. A true two dimensional Fourier transform may be instead performed through optics, as optical processing provides inherent parallel computing capabilities. By processing the azimuth and slant range directions simultaneously, a reduction in processing time and power is achieved. In addition, the configuration of the optics is such that high resolution images may be obtained at no additional processing cost. The optical SAR processor is also designed to adapt to SAR system parameter changes. It has the capability to produce full Envisat / ASAR scenes from the various image mode swaths (IS1 - IS7) within tens of seconds. This paper reviews the design of the real-time high resolution optical SAR processor prototype and discusses the results of images reconstructed from simulated point targets as well as from Envisat / ASAR data sets.
Blood Pressure, LDL Cholesterol, and Intima-Media Thickness (2000)

Abstract —The “response to injury” hypothesis is a plausible model of the development of atherosclerosis supported by observations from animal models. The present study uses epidemiological data to investigate the hypothesis that wall damage due to hypertension is a precursor of low density lipoprotein cholesterol (LDL-C)–mediated atherosclerosis. The Los Angeles Atherosclerosis Study is following a cohort of 576 participants who were aged 40 to 60 years and were free of symptomatic cardiovascular disease at recruitment. Common carotid artery intima-media thickness (IMT) was assessed by B-mode ultrasonography. After exclusion for nonfasting blood draw and other missing data, 511 subjects were available for analysis. IMT was regressed on LDL-C within tertiles of systolic blood pressure (SBP): low (93 to 122 mm Hg), middle (123 to 132 mm Hg), and high (133 to 175 mm Hg). Covariates were age, sex, body height, body mass index, ethnicity, smoking status, diabetes, and pharmacological treatment for hypertension or hypercholesterolemia. IMT was significantly related to LDL-C in the high SBP group (β=0.025±0.008, where β values are IMT [mm]/LDL-C [mmol/L]; P =0.002) but not in the middle (β=−0.006±0.008, P =0.39) or low (β=−0.004±0.009, P =0.64) SBP group. The slope in the high SBP group was significantly greater than in the middle ( P =0.004) or low ( P =0.014) SBP group. Results were similar for women and men, and after the exclusion of diabetics and persons using antihypertensive or lipid-lowering medications. Elevated LDL-C was associated with increased IMT in the upper tertile of SBP but not in the lower tertiles. These findings are consistent with the hypothesis that wall injury due to elevated SBP increases the susceptibility of the artery wall to LDL-C–mediated atherogenesis.
Life-threatening nonspherocytic hemolytic anemia in a patient with a null mutation in the PKLR gene and no compensatory PKM gene expression (2005)

Human erythrocyte R-type pyruvate kinase (RPK) deficiency is an autosomal recessive disorder produced by mutations in the PKLR gene, causing chronic nonspherocytic hemolytic anemia. Survival of patients with severe RPK deficiency has been associated with compensatory expression in red blood cells (RBCs) of M2PK, an isoenzyme showing wide tissue distribution. We describe a novel homozygous null mutation of the PKLR gene found in a girl with a prenatal diagnosis of PK deficiency. The mutant PK gene revealed an 11-nucleotide (nt) duplication at exon 8, causing frameshift of the PKLR transcript, predicting a truncated protein inferred to have no catalytic activity. Western blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) detected no M2PK expression in the peripheral blood red cell fraction. The expression of mutant RPK mRNA in the RBCs was almost 6 times higher than that detected in a control patient with hereditary spherocytosis. This molecular phenotypic analysis of the null mutation in the PKLR gene provides evidence for a lack of M2PK in the mature RBCs of this patient and suggests that normal red cell functions and survival are achieved through a population of young erythroid cells released into the circulation in response to anemia.
Wideband coding for uncoordinated multiple access communication (1992)

The paper reviews many of the coding techniques which have been proposed for use in spread-spectrum communication links. In these systems, narrow-band data accesses a common wideband channel, with each subscriber assigned to a unique access code. This code division multiple access (CDMA) system permits uncoordinated access to the channel with the interference level set by the total number of active subscribers. The paper investigates pseudo-noise (PN) and related sequence sets, specifically the auto- and crosscorrelation responses are examined both with and without data transmissions. These are quantified in terms of peak sidelobe errors, characteristic probability density functions and bit error ratio performance in the CDMA multi-user traffic environment. This allows the CDMA capacity to be predicted given the bit rate requirements, total available bandwidth and required bit error ratio
Antisense Oligonucleotides with Different Backbones (1999)

A novel, positive read-out assay that quantifies only sequence-specific nuclear activity of antisense oligonucleotides was used to evaluate morpholino and 2'-O-methyl sugar-phosphate oligonucleotides. The assay is based on modification of the splicing pathway of human beta-globin pre-mRNA. In addition, scrape-loading of cells with oligonucleotides allows the separate assessment of intracellular antisense activity of the oligonucleotides and their ability to penetrate the cell membrane barrier. The results show that, with scrape-loading, the morpholino oligonucleotides were approximately 3-fold more effective in their intrinsic antisense activity than alternating phosphodiester/phosphorothioate 2'-O-methyl-oligoribonucleotides and 6-9- and almost 200-fold more effective than the exclusively phosphorothioate and phosphodiester derivatives, respectively. The morpholino oligonucleotides were over 20-fold more effective than the phosphorothioate 2'-O-methyl-oligoribonucleotides in free uptake from the culture media. The antisense activity of the morpholino oligonucleotides was detectable not only in monolayer HeLa cells but also in suspension K562 cells. Time course experiments suggest that both the free uptake and efflux of morpholino oligonucleotides are slow.
Slowing DNA Translocation in a Solid-State Nanopore (2005)

Reducing a DNA molecule's translocation speed in a solid-state nanopore is a key step toward rapid single molecule identification. Here we demonstrate that DNA translocation speeds can be reduced by an order of magnitude over previous results. By controlling the electrolyte temperature, salt concentration, viscosity, and the electrical bias voltage across the nanopore, we obtain a 3 base/micros translocation speed for 3 kbp double-stranded DNA in a 4-8 nm diameter silicon nitride pore. Our results also indicate that the ionic conductivity inside such a nanopore is smaller than it is in bulk.