gebhart/patrepeval huggingface dataset:
Efficacy of Killed Virus Vaccine, Live Attenuated Chimeric Virus Vaccine, and Passive Immunization for Prevention ofWest Nile virusEncephalitis in Hamster Model (2002)

Results of experiments evaluating the efficacy of three immunization strategies for the prevention of West Nile virus (WNV) encephalitis are reported. Immunization strategies evaluated included a killed virus veterinary vaccine, a live attenuated chimeric virus vaccine candidate, and passive immunization with WNV-immune serum; all were tested by using a hamster model of the disease. Each product protected the animals from clinical illness and death when challenged with a hamster-virulent éwild-type WNV strain 1 month after initial immunization. The live attenuated chimeric virus vaccine candidate induced the highest humoral antibody responses, as measured by hemagglutination inhibition, complement fixation, and plaque reduction neutralization tests. Although the duration of protective immunity was not determined in this study, our preliminary results and the cumulative experience of other virus vaccines suggest that the live attenuated chimeric virus provides the longest lasting immunity.
High-Throughput Screening Approach for Nanoporous Materials Genome Using Topological Data Analysis: Application to Zeolites (2018)

The materials genome initiative has led to the creation of a large (over a million) database of different classes of nanoporous materials. As the number of hypothetical materials that can, in principle, be experimentally synthesized is infinite, a bottleneck in the use of these databases for the discovery of novel materials is the lack of efficient computational tools to analyze them. Current approaches use brute-force molecular simulations to generate thermodynamic data needed to predict the performance of these materials in different applications, but this approach is limited to the analysis of tens of thousands of structures due to computational intractability. As such, it is conceivable and even likely that the best nanoporous materials for any given application have yet to be discovered both experimentally and theoretically. In this article, we seek a computational approach to tackle this issue by transitioning away from brute-force characterization to high-throughput screening methods based on big-data analysis, using the zeolite database as an example. For identifying and comparing zeolites, we used a topological data analysis-based descriptor (TD) recognizing pore shapes. For methane storage and carbon capture applications, our analyses seeking pairs of highly similar zeolites discovered good correlations between performance properties of a seed zeolite and the corresponding pair, which demonstrates the capability of TD to predict performance properties. It was also shown that when some top zeolites are known, TD can be used to detect other high-performing materials as their neighbors with high probability. Finally, we performed high-throughput screening of zeolites based on TD. For methane storage (or carbon capture) applications, the promising sets from our screenings contained high-percentages of top-performing zeolites: 45% (or 23%) of the top 1% zeolites in the entire set. This result shows that our screening approach using TD is highly efficient in finding high-performing materials. We expect that this approach could easily be extended to other applications by simply adjusting one parameter, the size of the target gas molecule.
Radiation Protection Practices during the Helium Circulator Maintenance of the 10 MW High Temperature Gas-Cooled Reactor-Test Module (HTR-10) (2016)

Current radiation protection methodology offers abundant experiences on light-water reactors, but very few studies on high temperature gas-cooled reactor (HTR). To fill this gap, a comprehensive investigation was performed to the radiation protection practices in the helium circulator maintenance of the Chinese 10 MW HTR test module (HTR-10) in this paper. The investigation reveals the unique behaviour of HTR-10’s radiation sources in the maintenance as well as its radionuclide species and presents the radiation protection methods that were tailored to these features. Owing to these practices, the radioactivity level was kept low throughout the maintenance and only low-level radioactive waste was generated. The quantitative analysis further demonstrates that the decontamination efficiency was over 89% for surface contamination and over 34% for<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>γ</mml:mi></mml:mrow></mml:math>dose rate and the occupational exposure was much lower than both the limits of regulatory and the exposure levels in comparable literature. These results demonstrate the effectiveness of the reported radiation protection practices, which directly provides hands-on experience for the future HTR-PM reactor and adds to the completeness of the radiation protection methodology.
Norwalk Virus N-Terminal Nonstructural Protein Is Associated with Disassembly of the Golgi Complex in Transfected Cells (2004)

Norwalk virus is the prototype strain for members of the genus Norovirus in the family Caliciviridae, which are associated with epidemic gastroenteritis in humans. The nonstructural protein encoded in the N-terminal region of the first open reading frame (ORF1) of the Norwalk virus genome is analogous in gene order to proteins 2A and 2B of the picornaviruses; the latter is known for its membrane-associated activities. Confocal microscopy imaging of cells transfected with a vector plasmid that provided expression of the entire Norwalk virus N-terminal protein (amino acids 1 to 398 of the ORF1 polyprotein) showed colocalization of this protein with cellular proteins of the Golgi apparatus. Furthermore, this colocalization was characteristically associated with a visible disassembly of the Golgi complex into discrete aggregates. Deletion of a predicted hydrophobic region (amino acids 360 to 379) in a potential 2B-like (2BL) region (amino acids 301 to 398) near the C terminus of the Norwalk virus N-terminal protein reduced Golgi colocalization and disassembly. Confocal imaging was conducted to examine the expression characteristics of fusion proteins in which the 2BL region from the N-terminal protein of Norwalk virus (a genogroup I norovirus) or MD145 (a genogroup II norovirus) was fused to the C terminus of enhanced green fluorescent protein. Expression of each fusion protein in cells showed evidence for its colocalization with the Golgi apparatus. These data indicate that the N-terminal protein of Norwalk virus interacts with the Golgi apparatus and may play a 2BL role in the induction of intracellular membrane rearrangements associated with positive-strand RNA virus replication in cells.
Future Directions and Challenges for ETox Flash Memory Scaling (2004)

The physical and electrical scaling challenges for ETox/spl trade/ Flash memory, including reliability considerations, will be reviewed with potential directions for solutions identified. As Flash scales into the sub-100-nm regime, challenges arise due to the high voltage/field requirement of the programming and erase mechanisms and the stringent charge storage requirement of the dielectrics. These challenges will be overcome with innovations in new materials, new cell structures, and memory error management. Using these techniques will extend the viability of Flash memory to at least the 45-nm generation.
Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan (2016)

Nanoliposomal irinotecan (nal-IRI) was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy) trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin) in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in survival.
Specific inhibition of human β‐D‐glucuronidase and α‐L‐iduronidase by a trihydroxy pipecolic acid of plant origin (1984)

The glucuronic acid analogue of 1-deoxynojirimycin, 2(S)-carboxy-3(R), 4(R), 5(S)-trihydroxypiperidine, recently isolated from seeds of Baphia racemosa, is a novel specific inhibitor of human liver beta-D-glucuronidase and alpha-L-iduronidase. No other glycosidases are inhibited. The inhibition of beta-D-glucuronidase is competitive, with a Ki of 8 X 10(-5) M and is pH-dependent. This inhibitor may be useful to induce a mucopolysaccharidosis or to investigate the function of microsomal beta-D-glucuronidase.
Signal recovery from random projections (2005)

Can we recover a signal <i>f</i>&isin;R<sup>N</sup> from a small number of linear measurements? A series of recent papers developed a collection of results showing that it is surprisingly possible to reconstruct certain types of signals accurately from limited measurements. In a nutshell, suppose that <i>f</i> is compressible in the sense that it is well-approximated by a linear combination of <i>M</i> vectors taken from a known basis &Psi;. Then not knowing anything in advance about the signal, <i>f</i> can (very nearly) be recovered from about <i>M</i> log <i>N</i> generic nonadaptive measurements only. The recovery procedure is concrete and consists in solving a simple convex optimization program. In this paper, we show that these ideas are of practical significance. Inspired by theoretical developments, we propose a series of practical recovery procedures and test them on a series of signals and images which are known to be well approximated in wavelet bases. We demonstrate that it is empirically possible to recover an object from about 3<i>M</i>-5<i>M</i> projections onto <i>generically chosen</i> vectors with an accuracy which is as good as that obtained by the ideal <i>M</i>-term wavelet approximation. We briefly discuss possible implications in the areas of data compression and medical imaging.
Preparation of Chitosan/Polyglutamic Acid Spheres Based on the Use of Polystyrene Template as a Nonviral Gene Carrier (2009)

The major difficulty in designing carrier system for gene delivery is finding a good compromise between structure, stability, and efficiency. Current carrier systems are limited in terms of release kinetics, toxicity, and overall capacity to carry biomolecules. The objectives of this study were to develop a process of producing biodegradable polymer-based hollow spheres and to characterize their potential use as carriers of plasmid DNA (pDNA) for gene delivery. The method developed involves coating a template with a polymer layer. After the removal of the template, a hollow core is obtained. Specifically, the production process begins with chitosan coating and is followed by polyglutamic acid cross-linking. The advantage of this production process is that it could be applied to a variety of polymeric systems. Because the hollow polymer structures can encapsulate a large variety of guest molecules, these spheres have significant potential for delivery. After physical characterization, the ability of the spheres to encapsulate and retain pDNA was investigated. The chitosan/polyglutamic acid spheres were used to encapsulate pDNA with up to 90% efficiency, and the encapsulated pDNA was retained for 3 days without degradation in 10% fetal bovine serum (FBS)-complemented media and released up to 30% after 3 days in the presence of the lysozyme, suggesting that these spheres represent an attractive method for gene delivery.
Chemokines CCL3/MIP1α, CCL5/RANTES and CCL18/PARC are Independent Risk Predictors of Short-Term Mortality in Patients with Acute Coronary Syndromes (2012)

Cytokines play an important role in ischemic injury and repair. However, little is known about their prognostic value in cardiovascular disease. The aim of this study was to investigate the prognostic importance of chemokines CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC for the risk of future cardiovascular events in patients with acute coronary syndromes (ACS). Baseline levels of CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC were determined in ACS patients from the Bad Nauheim ACS II registry (n = 609). During the following 200 days, patients were monitored for the occurrence of fatal and non-fatal cardiovascular events. Patients with CCL3/MIP1α, CCL5/RANTES and CCL18/PARC concentrations in the highest tertile were associated with an increased risk of a fatal event during follow-up (HR: 2.19, 95%CI: 1.04-4.61 for CCL3/MIP1α, HR: 3.45, 95%CI: 1.54-7.72 for CCL5/RANTES and HR: 3.14, 95%CI: 1.33-7.46 for CCL18/PARC). This risk was highest for patients with all three biomarkers concentrations in the upper tertile (HR: 2.52, 95%CI: 1.11-5.65). Together with known risk predictors of cardiovascular events, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC combined improved the c-statistics from 0.74 to 0.81 (p = 0.007). In conclusion, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC are independently associated with the risk of short-term mortality in ACS patients. Combining all three biomarkers further increased their prognostic value.
Intestinal microbiota and metabolites—Implications for broiler chicken health and performance (2013)

Microbiota in the intestine of an animal species has evolved together with the host. This coevolution has produced specific host-microbe combinations, called superorganisms, with the best possible fitness in a given environment. Intestinal microbiota has an enormous metabolic potential and it affects both the nutrition and health of the host. The importance of intestinal microbiota for the performance of broiler chickens has been studied for decades. The microbial community structure of the cecum is significantly more complex and less well characterized than that of the crop and small intestine. Culture-independent molecular techniques have recently been introduced to bring fresh insights into the intestinal system of the broiler chicken. As a consequence, there is growing evidence of connection between the apparent metabolizable energy of the diet and microbiota composition in the hindgut of the host. This connection can be due to direct conversion of some dietary components into high-energy metabolites by specialized bacteria. The utilization of such fermentation end products would provide more energy for the host, which could be measured as improved feed conversion efficiency. However, it is also possible that cecal microbial profile is a reflection of feed digestion and nutrient absorption efficiency in the proximal intestine. Disorders in these functions cause excess nutrient bypass to the lower intestine, providing new, easily available substrates for bacteria that could otherwise not compete in that habitat. The 2 causal links described are likely to coexist in real life situations, but their relative dominance warrants further well-designed studies.
Minireview: Epigenetic Alterations in Human Prostate Cancers (2009)

Human prostate cancer cells carry a myriad of genome defects, including both genetic and epigenetic alterations. These changes, which can be maintained through mitosis, generate malignant phenotypes capable of selective growth, survival, invasion, and metastasis. During prostatic carcinogenesis, epigenetic changes arise earlier than genetic defects, linking the appearance of epigenetic alterations in some way to disease etiology. The most common genetic defect thus far described, leading to fusion transcripts between the androgen-regulated gene TMPRSS2 and genes from the ETS family of transcription factors, likely endows prostate cancer cells with the ability to co-opt androgen signaling, the major prostate differentiation pathway, to support the malignant phenotype. Whether epigenetic changes promote the appearance of TMPRSS2-ETS family fusion transcripts or collaborate with fusion transcript expression in the pathogenesis of prostate cancer has not been established. However, a growing list of epigenetic alterations has provided new opportunities for clinical tests that might aid in prostate cancer screening, detection, diagnosis, staging, and risk stratification. The epigenetic changes appear to be more attractive than genetic changes as prostate cancer biomarkers because epigenetic alterations are present in a greater fraction of prostate cancer cases than any of the known genetic defects. In addition, an emerging generation of assay strategies for detection of specific DNA sequences carrying (5-me)C, the major epigenetic genome mark, has pushed somatic epigenetic alterations to the forefront of molecular biomarker assay development for cancer. Finally, a growing portfolio of epigenetic drugs, capable of reversing the phenotypic consequences of somatic epigenetic defects, has entered clinical trials for prostate cancer in the search for a new rational therapy for the disease.
Naturally occurring genotypes of the human immunodeficiency virus type 1 long terminal repeat display a wide range of basal and Tat-induced transcriptional activities (1994)

The primary body of information on the structure of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)/gag leader genotypes has been determined from the analysis of cocultivated isolates. Functional studies of this regulatory portion of the provirus have been derived from the study of in vitro-generated mutations of laboratory-adapted molecular clones of HIV-1. We have performed a longitudinal analysis of molecular clones from the LTR/gag leader region amplified directly from the peripheral blood of four patients over three years. We have found a remarkable number of point mutations and length polymorphisms in cis- and trans-acting regulatory elements within this cohort. Most of the length polymorphisms were associated with duplications of Sp1 and TCF-1 alpha sequences. These mutations were associated with a wide range of transcriptional activities for these genotypes in a reporter gene assay. Mutations in conserved Sp1 sequences correlated with a diminished capacity of such genotypes to bind purified Sp1 protein. Although no generalized trend in transcriptional activity was seen, a single patient accumulated mutations in NF-kappa B, Sp1, and TAR elements over this period. The analysis of naturally occurring mutations of LTR genotypes provides a means to study the molecular genetic consequences of virus-host interactions and to assess the functional impact of HIV therapeutics.
Isolation of Mesenchymal Stem Cells from Human Deciduous Teeth Pulp (2017)

This study aimed to identify predictors of success rate of mesenchymal stem cell (MSC) isolation from human deciduous teeth pulp. A total of 161 deciduous teeth were extracted at the dental clinic of Chang Gung Memorial Hospital. The MSCs were isolated from dental pulps using a standard protocol. In total, 128 colonies of MSCs were obtained and the success rate was 79.5%. Compared to teeth not yielding MSCs successfully, those successfully yielding MSCs were found to have less severe dental caries (no/mild-to-moderate/severe: 63.3/24.2/12.5% versus 12.5/42.4/42.4%, <i>P</i> < 0.001) and less frequent pulpitis (no/yes: 95.3/4.7% versus 51.5/48.5%, <i>P</i> < 0.001). In a multivariate regression model, it was confirmed that the absence of dental caries (OR = 4.741, 95% CI = 1.564-14.371, <i>P</i> = 0.006) and pulpitis (OR = 9.111, 95% CI = 2.921-28.420, <i>P</i> < 0.001) was significant determinants of the successful procurement of MSCs. MSCs derived from pulps with pulpitis expressed longer colony doubling time than pulps without pulpitis. Furthermore, there were higher expressions of proinflammatory cytokines, interleukin- (IL-) 6 and monocyte chemoattractant protein- (MCP-) 1, <i>P</i> < 0.01, and innate immune response [toll-like receptor 1 (TLR1) and TLR8, <i>P</i> < 0.05; TLR2, TLR3, and TLR6, <i>P</i> < 0.01] in the inflamed than noninflamed pulps. Therefore, a carious deciduous tooth or tooth with pulpitis was relatively unsuitable for MSC processing and isolation.
MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If (2001)

Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients' fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation. Transfer of incomplete oligosaccharides to protein was detected. Sequence analysis of the Lec35/MPDU1 gene, known to be involved in the use of dolichylphosphomannose and dolichylphosphoglucose, revealed mutations in all three patients. Retroviral-based expression of the normal Lec35 cDNA in primary fibroblasts of patients restored normal lipid-linked oligosaccharide biosynthesis. We concluded that mutations in the Lec35/MPDU1 gene cause CDG. This novel type was termed CDG-If.
H-2Dd exploits a four residue peptide binding motif. (1993)

We have characterized the amino acid sequences of over 20 endogenous peptides bound by a soluble analog of H-2Dd, H-2Dds. Synthetic analogs corresponding to self, viral, tumor, or motif peptides were then tested for their ability to bind to H-2Dd by serologic epitope induction assays using both purified soluble protein and cell surface H-2Dd. The dominant primary sequence motif included glycine at position 2, proline at position 3, and a hydrophobic COOH terminus: leucine, isoleucine, or phenylalanine at position 9 or 10. Ancillary support for high affinity binding was contributed by a positively charged residue at position 5. Three-dimensional computer models of H-2Dds/peptide complexes, based on the crystallographic structure of the human HLA-B27/peptide complex, showed that the basic residue at position 5 was in position to form a salt bridge with aspartic acid at position 156, a polymorphic residue of the H-2Dd heavy (H) chain. Analysis of 28 such models, including 17 based on nonamer self-peptides, revealed considerable variation in the structure of the major histocompatibility complex (MHC) surrounding peptide residue 1, depending on the size and charge of the side chain. Interactions between the side chains of peptide residues 5 and 7, and 6 and 8 commonly occurred. Those peptide positions with limited sequence variability and least solvent accessibility may satisfy structural requirements for high affinity binding of the peptide to the MHC class I H chain, whereas the highly variable positions of the peptide (such as positions 4, 6, and 8) may contribute more to the T cell epitopes.