8 results on '"Lee, Chris"'
Search Results
2. Human evaluation of automatically generated text: Current trends and best practice guidelines.
- Author
-
van der Lee, Chris, Gatt, Albert, van Miltenburg, Emiel, and Krahmer, Emiel
- Subjects
- *
NATURAL language processing , *EVALUATION research , *BEHAVIORAL sciences , *BEST practices , *GUIDELINES - Abstract
• The current paper provides an overview of human evaluation practices in NLG. • The current paper gives an overview of the steps necessary to undertake a human evaluation study. • Building on findings from NLG, but also statistics and the behavioral sciences, the current paper provides a set of recommendations and best practices for human evaluation in NLG. Currently, there is little agreement as to how Natural Language Generation (NLG) systems should be evaluated, with a particularly high degree of variation in the way that human evaluation is carried out. This paper provides an overview of how (mostly intrinsic) human evaluation is currently conducted and presents a set of best practices, grounded in the literature. These best practices are also linked to the stages that researchers go through when conducting an evaluation research (planning stage; execution and release stage), and the specific steps in these stages. With this paper, we hope to contribute to the quality and consistency of human evaluations in NLG. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. Cell modeling and assay development for Krabbe disease.
- Author
-
Lee, Chris W., Manavalan, Arulmani, Ching, Wai Y., Herdt, Aimee R., Hong, Xinying, and Gelb, Michael H.
- Subjects
- *
PROTEIN precursors , *MISSENSE mutation , *DELETION mutation , *CELLS , *LYSOSOMAL storage diseases - Published
- 2020
- Full Text
- View/download PDF
4. Pharmacological chaperone therapeutics for Krabbe disease.
- Author
-
Lee, Chris W., Manavalan, Arulmani, and Clausen, Dana
- Subjects
- *
MOLECULAR chaperones , *GLOBOID cell leukodystrophy , *NERVE tissue , *DEGENERATION (Pathology) , *DNA mutational analysis - Abstract
Loss-of-function mutations in the galactcerebrosidase (GALC) lead to the development of Krabbe disease, a degenerative disorder characterized by progressive demyelination and neuroinflammation. More than 100 mutations have been identified in Krabbe disease patients including deletions, frameshift mutations, nonsense mutations and missense mutations. Positive disease diagnosis is confirmed by low GALC enzymatic activity in blood sample and mutational analysis of the GALC gene. More than 20 pathogenic GALC mutations have been determined to be missense mutations, which impair GALC protein function by altering the catalytic site and/or folded structure, which leads to protein mistrafficking. In these patients, GALC protein is present but inactive, or missing from the lysosome, respectively. Most disease-associated missense mutations are distant from GALC's catalytic site, which suggests that the mutant proteins will retain some catalytic activity if they can be stabilized enough to properly fold and/or be transported to the lysosome. Pharmacological chaperone (PC) is an emerging class of small-molecule therapeutics that can stabilize protein structure and restore function in enzymes with a missense mutation. In 2010 we identified one of the first PC candidates for Krabbe disease, α-lobeline (LB). This natural compound was found to partially correct the function of the GALC D544N mutant protein in a human cell-based assay. Later, it has also demonstrated by other group that LB can increase the activity of several other GALC mutants (G553R, E130K, N295T and G57S) in patient's fibroblasts. These results and others suggest that LB and other PC-based molecules may restore the function of a broad spectrum of GALC mutants. Therefore, we hypothesize that GALC missense mutations that cause protein misfolding, but maintain catalytic potential, are amenable to functional correction by LB and other PC candidates. We will present the results of our initial effort to identify amenable mutations and new potential PC candidates for therapeutic development. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
5. Structure Analysis of Peptide Deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: Snapshots of the Oxygen Sensitivity of Peptide Deformylase
- Author
-
Kreusch, Andreas, Spraggon, Glen, Lee, Chris C., Klock, Heath, McMullan, Daniel, Ng, Ken, Shin, Tanya, Vincent, Juli, Warner, Ian, Ericson, Christer, and Lesley, Scott A.
- Subjects
- *
ANTIBIOTICS , *ENZYMES - Abstract
Peptide deformylase (PDF) has received considerable attention during the last few years as a potential target for a new type of antibiotics. It is an essential enzyme in eubacteria for the removal of the formyl group from the N terminus of the nascent polypeptide chain. We have solved the X-ray structures of four members of this enzyme family, two from the Gram-positive pathogens Streptococcus pneumoniae and Staphylococcus aureus, and two from the Gram-negative bacteria Thermotoga maritima and Pseudomonas aeruginosa. Combined with the known structures from the Escherichia coli enzyme and the recently solved structure of the eukaryotic deformylase from Plasmodium falciparum, a complete picture of the peptide deformylase structure and function relationship is emerging. This understanding could help guide a more rational design of inhibitors.A structure-based comparison between PDFs reveals some conserved differences between type I and type II enzymes. Moreover, our structures provide insights into the known instability of PDF caused by oxidation of the metal-ligating cysteine residue. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
6. Galactosylceramidase deficiency and pathological abnormalities in cerebral white matter of Krabbe disease.
- Author
-
Iacono, Diego, Koga, Shunsuke, Peng, Hui, Manavalan, Arulmani, Daiker, Jessica, Castanedes-Casey, Monica, Martin, Nicholas B., Herdt, Aimee R., Gelb, Michael H., Dickson, Dennis W., and Lee, Chris W.
- Subjects
- *
LEUKOENCEPHALOPATHIES , *PERIPHERAL nervous system , *GLYCOGEN storage disease type II , *IMMOBILIZED proteins , *MEMBRANE proteins , *CENTRAL nervous system - Abstract
Krabbe Disease (KD) is an autosomal recessive disorder that results from loss-of-function mutations in the GALC gene, which encodes lysosomal enzyme galactosylceramidase (GALC). Functional deficiency of GALC is toxic to myelin-producing cells, which leads to progressive demyelination in both the central and peripheral nervous systems. It is hypothesized that accumulation of psychosine, which can only be degraded by GALC, is a primary initiator of pathologic cascades. Despite the central role of GALC in KD pathomechanism, investigations of GALC deficiency at a protein level are largely absent, due in part, to the lack of sensitive antibodies in the field. Leveraging two custom antibodies that can detect GALC at endogenous levels, we demonstrated that GALC protein is predominantly localized to oligodendrocytes in cerebral white matter of an infant brain, consistent with its functional role in myelination. Mature GALC could also be quantitatively detected as a 26 kDa band by western blotting and correlated to enzyme activity in brain tissues. The p.Ile562Thr polymorphic variant, which is over-represented in the KD population, was associated with reduced mature GALC protein and activity. In three infantile KD cases, homozygous null mutations in GALC lead to deficiency in total GALC protein and activity. Interestingly, although GALC activity was absent, normal levels of total GALC protein were detected by a sandwich ELISA using our custom antibodies in a later-onset KD brain, which suggests that the assay has the potential to differentiate infantile- and later-onset KD cases. Among the infantile KD cases, we quantified a 5-fold increase in psychosine levels, and observed increased levels of acid ceramidase, a key enzyme for psychosine production, and hyperglycosylated lysosomal-associated membrane protein 1, a marker for lysosomal activation, in periventricular white matter, a major pathological brain region, when compared with age-matched normal controls. While near complete demyelination was observed in these cases, we quantified that an early-infantile case (age of death at 10 months) had about 3-fold increases in both globoid cells, a pathological hallmark for KD, and CD8-positive T lymphocytes, a pathological marker for multiple sclerosis, in the white matter when compared with a slower progressing infantile case (age of death at 21 months), which suggests a positive correlation between clinical severity and neuropathology. Taken together, our findings have advanced the understanding of GALC protein biology in the context of normal and KD brain white matter. We also revealed new neuropathological changes that may provide insights to understand KD pathogenesis. [Display omitted] • GALC protein is localized to oligodendrocytes in white matter of an infant brain. • The GALC p.Ile562Thr variant reduced mature GALC protein level and GALC activity. • A novel GALC ELISA distinguishes between later-onset and infantile KD cases. • Psychosine, ASAH1 and hyperglycosylated LAMP1 were elevated in infantile KD brains. • More globoid cells and CD8 + ve T cells were detected in the most severe KD case. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. Paraspinous muscle as a predictor of surgical outcome.
- Author
-
Canvasser, Leah D., Mazurek, Alyssa A., Cron, David C., Terjimanian, Michael N., Chang, Eric T., Lee, Chris S., Alameddine, Mitchell B., Claflin, Jake, Davis, Elyse D., Schumacher, Tucker M., Wang, Stewart C., and Englesbe, Michael J.
- Subjects
- *
PREDICTION theory , *PSOAS muscles , *MORTALITY , *LOGISTIC regression analysis , *STANDARD deviations , *MORPHOMETRICS , *RISK assessment - Abstract
Background Objective measures for preoperative risk assessment are needed to inform surgical risk stratification. Previous studies using preoperative imaging have shown that the psoas muscle is a significant predictor of postoperative outcomes. Because psoas measurements are not always available, additional trunk muscles should be identified as alternative measures of risk assessment. Our research assessed the relationship between paraspinous muscle area, psoas muscle area, and surgical outcomes. Methods Using the Michigan Surgical Quality Collaborative database, we retrospectively identified 1309 surgical patients who had preoperative abdominal computerized tomography scans within 90 d of operation. Analytic morphomic techniques were used to measure the cross-sectional area of the paraspinous muscle at the T12 vertebral level. The primary outcome was 1-y mortality. Analyses were stratified by sex, and logistic regression was used to assess the relationship between muscle area and postoperative outcome. Results The measurements of paraspinous muscle area at T12 were normally distributed. There was a strong correlation between paraspinous muscle area at T12 and total psoas area at L4 (r = 0.72, P <0.001). Paraspinous area was significantly associated with 1-y mortality in both females (odds ratio = 0.70 per standard deviation increase in paraspinous area, 95% confidence interval 0.50-0.99, P = 0.046) and males (odds ratio = 0.64, 95% confidence interval 0.47-0.88, P = 0.006). Conclusions Paraspinous muscle area correlates with psoas muscle area, and larger paraspinous muscle area is associated with lower mortality rates after surgery. This suggests that the paraspinous muscle may be an alternative to the psoas muscle in the context of objective measures of risk stratification. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
8. F.88. Using Forward Genetics to Identify Regulators of Autoimmunity: Altered B-Cell Function and Glomerulonephritis in the Lyn Mutant Weeb
- Author
-
barouch-Bentov, Rina, Hermanl Kim Sungjoon, Ann, Velentza, Anastasia, Ziaee, Niusha, Lee, Chris, Liu, Yi, Cooke, Mike, and Sauer, Karsten
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.