gebhart/patrepeval huggingface dataset:
Environment‐ and mutation‐dependent aggregation behavior of Alzheimer amyloid β‐protein (2004)

The deposition of amyloid beta-protein in the brain is a fundamental process in the development of Alzheimerís disease; however, the mechanism underlying aggregation of amyloid beta-protein remains to be determined. Here, we report that a membrane-mimicking environment, generated in the presence of detergents or a ganglioside, is sufficient per se for amyloid fibril formation from soluble amyloid beta-protein. Furthermore, hereditary variants of amyloid beta-protein, which are caused by amyloid precursor protein gene mutations, including the Dutch (E693Q), Flemish (A692G) and Arctic (E693G) types, show mutually different aggregation behavior in these environments. Notably, the Arctic-type amyloid beta-protein, in contrast to the wild-type and other variant forms, shows a markedly rapid and higher level of amyloid fibril formation in the presence of sodium dodecyl sulfate or GM1 ganglioside. These results suggest that there are favorable local environments for fibrillogenesis of amyloid beta-protein.
Tricyclic 2'-Deoxycytidine Analogs: Syntheses and Incorporation into Oligodeoxynucleotides Which Have Enhanced Binding to Complementary RNA (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTricyclic 2'-Deoxycytidine Analogs: Syntheses and Incorporation into Oligodeoxynucleotides Which Have Enhanced Binding to Complementary RNAKuei-Ying Lin, Robert J. Jones, and Mark MatteucciCite this: J. Am. Chem. Soc. 1995, 117, 13, 3873–3874Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ja00118a026https://doi.org/10.1021/ja00118a026research-articleACS PublicationsRequest reuse permissionsArticle Views948Altmetric-Citations136LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Characterization of glucosinolate—myrosinase system in developing salt cress Thellungiella halophila (2009)

Glucosinolates are specialized plant metabolites derived from amino acids. They can be hydrolyzed by myrosinases into different degradation products, which have a variety of biological activities. In this study, the compositions and contents of glucosinolates in salt cress (Thellungiella halophila) at different developmental stages were analyzed by high performance liquid chromatography and mass spectrometry (HPLC-MS). Myrosinase activities were also measured. Seven glucosinolates were identified in T. halophila throughout its life cycle. The glucosinolate profiles varied significantly among different tissues. The roots at stage 4 contained the highest concentrations of total, aromatic and indole glucosinolates among all tissues. Whereas roots, flowers and siliques contained all seven glucosinolates, seeds contained only four aliphatic glucosinolates. During development, the concentrations also displayed significant changes. From seeds to cotyledons and from stage 4 roots to stage 5 roots, there were dramatic declines of glucosinolates, which correlated well with changes in myrosinase activities. In other tissues, myrosinase activity alone could not explain the glucosinolate concentration changes. Certain tissues of T. halophila contained Arabidopsis myrosinase TGG1 and TGG2 orthologs. The molecular basis and functional significance of our findings are discussed here.
Up‐regulation of macrophage migration inhibitory factor in infants with acute neonatal necrotizing enterocolitis (2005)

MIF acts by stimulating macrophage production of IL-6 and IL-8. This further aggravates the inflammatory process by increasing the infiltration of neutrophils and activating inflammatory cells. The results of this study suggest that MIF plays an important role in the pathogenesis of NEC and may serve as a target for therapeutic intervention in NEC.
Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells (2012)

We control hPSC differentiation into synthetic or contractile phenotypes by using appropriate concentrations of relevant factors. Deriving Con-vSMCs from an integration-free hiPSC line may prove useful for regenerative therapy involving blood vessel differentiation and stabilization.
Cloning, Expression, and Substrate Specificity of a Fungal Chymotrypsin (2000)

Unlike trypsins, chymotrypsins have not until now been found in fungi. Expressed sequence tag analysis of the deuteromycete Metarhizium anisopliae identified two trypsins (family S1) and a novel chymotrypsin (CHY1). CHY1 resembles actinomycete (bacterial) chymotrypsins (family S2) rather than other eukaryote enzymes (family S1) in being synthesized as a precursor species (374 amino acids, pI/MW: 5.07/38,279) containing a large N-terminal fragment (186 amino acids). Chy1 was expressed in Pichia pastoris yielding an enzyme with a chymotrypsin specificity for branched aliphatic and aromatic C-terminal amino acids. This is predictable as key catalytic residues determining the specificity of Streptomyces griseus chymotrypsins are conserved with CHY1. Mature (secreted) CHY1 (pI/MW: 8.29/18,499) shows closest overall amino acid identity to S. griseus protease C (55%) and clustered with other secreted bacterial S2 chymotrypsins that diverged widely from animal and endocellular bacterial enzymes in phylogenetic trees of the chymotrypsin superfamily. Conversely, actinomycete chymotrypsins are much more closely related to fungal proteases than to other eubacterial sequences. Complete genomes of yeast, gram eubacteria, archaebacteria, and mitochondria do not contain paralogous genes. Expressed sequence tag data bases from other fungi also lack chymotrypsin homologs. In light of this patchy distribution, we conclude that chy1 probably arose by lateral gene transfer from an actinomycete bacterium.
A new murine monoclonal antibody, CMU10, as a marker for colonic carcinoma and precancerous conditions. (1995)

Because CMU10 differentially recognizes an antigen in cancerous and precancerous tissues, but not in normal tissues, it may be useful as a tumor marker for immunodiagnosis and, hence, early detection.
Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. (2002)

The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better biomarkers for early detection of PCA using protein profiling technologies that can simultaneously resolve and analyze multiple proteins. Evaluating multiple proteins will be essential to establishing signature proteomic patterns that distinguish cancer from noncancer as well as identify all genetic subtypes of the cancer and their biological activity. In this study, we used a protein biochip surface enhanced laser desorption/ionization mass spectrometry approach coupled with an artificial intelligence learning algorithm to differentiate PCA from noncancer cohorts. Surface enhanced laser desorption/ionization mass spectrometry protein profiles of serum from 167 PCA patients, 77 patients with benign prostate hyperplasia, and 82 age-matched unaffected healthy men were used to train and develop a decision tree classification algorithm that used a nine-protein mass pattern that correctly classified 96% of the samples. A blinded test set, separated from the training set by a stratified random sampling before the analysis, was used to determine the sensitivity and specificity of the classification system. A sensitivity of 83%, a specificity of 97%, and a positive predictive value of 96% for the study population and 91% for the general population were obtained when comparing the PCA versus noncancer (benign prostate hyperplasia/healthy men) groups. This high-throughput proteomic classification system will provide a highly accurate and innovative approach for the early detection/diagnosis of PCA.
Optimization and Functional Effects of Stable Short Hairpin RNA Expression in Primary Human Lymphocytes via Lentiviral Vectors (2006)

Specific, potent, and sustained short hairpin RNA (shRNA)-mediated gene silencing is crucial for the successful application of RNA interference technology to therapeutic interventions. We examined the effects of shRNA expression in primary human lymphocytes (PBLs) using lentiviral vectors bearing different RNA polymerase III promoters. We found that the U6 promoter is more efficient than the H1 promoter for shRNA expression and for reducing expression of CCR5 in PBLs. However, shRNA expression from the U6 promoter resulted in a gradual decline of the transduced cell populations. With one CCR5 shRNA this decline could be attributed to elevated apoptosis but another CCR5 shRNA that caused cytotoxicity did not show evidence of apoptosis, suggesting sequence-specific mechanisms for cytotoxicity. In contrast to the U6 promoter, PBLs transduced by vectors expressing shRNAs from the H1 promoter could be maintained without major cytotoxic effects. Since a lower level of shRNA expression appears to be advantageous to maintaining the shRNA-transduced population, lentiviral vectors bearing the H1 promoter are more suitable for stable transduction and expression of shRNA in primary human T lymphocytes. Our results suggest that functional shRNA screens should include tests for both potency and adverse metabolic effects upon primary cells.
A simulation-based approach to architectural verification of multiprocessor systems (2002)

This paper presents a simulation-based method for verifying coherency in weakly ordered shared memory multiprocessor systems. This methodology requires minimal assumptions regarding the implementation details, such as the coherence protocol and cache line replacement rules. Independence from implementation details for architectural verification is achieved via a technique called data-coloring. The non-determinism arising from weak ordering is resolved by introducing the notion of valid sets for checking the correctness of memory operations. We contrast our approach with other methods that have been prevalent in the industry and provide implementation details and an example implementation of our methodology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thrombin Activates Factor XI on Activated Platelets in the Absence of Factor XII (1999)

Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides. However, a physiological cofactor for thrombin activation of factor XI has not been identified. We examined this question in a cell-based, tissue factor-initiated model system. In the absence of factor XII, factor XI enhanced thrombin generation in this model. The effect on thrombin generation was reproduced by 2 to 5 pmol/L factor XIa. A specific inhibitor of factor XIIa did not diminish the effect of factor XI. Thus, factor XI can be activated in a model system that does not contain factor XIIa or nonphysiological cofactors. Preincubation of factor XI with activated platelets and thrombin or factor Xa enhanced subsequent thrombin generation in the model system. Preincubation of factor XI with thrombin or factor Xa, but without platelets, did not enhance thrombin generation, suggesting that these proteases might activate factor XI on platelet surfaces. Thrombin and factor Xa were then directly tested for their ability to activate factor XI. In the presence of dextran sulfate, thrombin or factor Xa activated factor XI. Thrombin, but not factor Xa, also cleaved detectable amounts of factor XI in the presence of activated platelets. Thus, thrombin activates enough factor XI to enhance subsequent thrombin generation in a model system. Platelet surfaces might provide the site for thrombin activation of functionally significant amounts of factor XI in vivo.
A mode-filtering scheme for improvement of the bandwidth-distance product in multimode fiber systems (1993)

A scheme in which the bandwidth-distance product of a multimode fiber is extended, so that it can nearly support the transmission rate of single-mode systems, is studied. It is based on selective launching of lower order modes into the fiber at the transmitting end and on filtering out at the receiver the fraction of the energy that was coupled into the higher order modes throughout the propagation in the multimode fiber. The power penalty and the dispersion performance of the scheme are investigated. In particular, it is shown that the scheme carries about 6.5 dB penalty, and doubling of the bandwidth*distance value is demonstrated. The effect of splices on the performance is also presented. It is envisioned that this approach may be used to upgrade existing multimode systems without the need for rewiring. For example, it can be used to replace the FDDI (fiber distributed data interface) installations in future high-speed networks, when transmission rates increase from megabits per second to gigabits per second.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Learning from Maps: Visual Common Sense for Autonomous Driving (2016)

Today's autonomous vehicles rely extensively on high-definition 3D maps to navigate the environment. While this approach works well when these maps are completely up-to-date, safe autonomous vehicles must be able to corroborate the map's information via a real time sensor-based system. Our goal in this work is to develop a model for road layout inference given imagery from on-board cameras, without any reliance on high-definition maps. However, no sufficient dataset for training such a model exists. Here, we leverage the availability of standard navigation maps and corresponding street view images to construct an automatically labeled, large-scale dataset for this complex scene understanding problem. By matching road vectors and metadata from navigation maps with Google Street View images, we can assign ground truth road layout attributes (e.g., distance to an intersection, one-way vs. two-way street) to the images. We then train deep convolutional networks to predict these road layout attributes given a single monocular RGB image. Experimental evaluation demonstrates that our model learns to correctly infer the road attributes using only panoramas captured by car-mounted cameras as input. Additionally, our results indicate that this method may be suitable to the novel application of recommending safety improvements to infrastructure (e.g., suggesting an alternative speed limit for a street).
Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains (2020)

The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.
Rapid and Efficient Generation of Neurons from Human Pluripotent Stem Cells in a Multititre Plate Format (2013)

Existing protocols for the generation of neurons from human pluripotent stem cells (hPSCs) are often tedious in that they are multistep procedures involving the isolation and expansion of neural precursor cells, prior to terminal differentiation. In comparison to these time-consuming approaches, we have recently found that combined inhibition of three signaling pathways, TGFβ/SMAD2, BMP/SMAD1, and FGF/ERK, promotes rapid induction of neuroectoderm from hPSCs, followed by immediate differentiation into functional neurons. Here, we have adapted our procedure to a novel multititre plate format, to further enhance its reproducibility and to make it compatible with mid-throughput applications. It comprises four days of neuroectoderm formation in floating spheres (embryoid bodies), followed by a further four days of differentiation into neurons under adherent conditions. Most cells obtained with this protocol appear to be bipolar sensory neurons. Moreover, the procedure is highly efficient, does not require particular expert skills, and is based on a simple chemically defined medium with cost-efficient small molecules. Due to these features, the procedure may serve as a useful platform for further functional investigation as well as for cell-based screening approaches requiring human sensory neurons or neurons of any type.
Preventing Opioid-Related Deaths in Children Undergoing Surgery (2012)

Tonsillectomy is one of the most commonly done surgical procedures in children. There are many unreported deaths following tonsillectomy in children due to opioids. Genetic variations in liver microenzyme, CYP2D6, had been associated with some of the deaths. Opioids metabolized by CYP2D6 include codeine, tramadol, hydrocodone, and oxycodone. Ultrarapid metabolizers and some extensive metabolizers of CYP2D6 relatively produce more active opioid metabolites resulting in life-threatening adverse effects, especially in young children. Young and obese children with history of sleep apnea are at higher risk of developing serious opioid-related respiratory depression. The adverse outcomes can be avoided and the safety of pain management can be improved by CYP2D6 genetic testing before prescribing these opioids or by using alternative analgesics.
A New Metal Control Gate Last process (MCGL process) for high performance DC-SF (Dual Control gate with Surrounding Floating gate) 3D NAND flash memory (2012)

A new Metal Control Gate Last process (MCGL process) has been successfully developed for the DC-SF (Dual Control gate with Surrounding Floating gate cell)[1] three-dimensional (3D) NAND flash memory. The MCGL process can realize a low resistive tungsten (W) metal word-line with high-k IPD, a low damage on tunnel oxide/IPD, and a preferable FG shape. And also, a conventional bulk erase can be used, replaced GIDL erase in BiCS[3][4], due to direct connection between channel poly and p-well by the channel contact holes. Therefore, by using MCGL process, high performance and high reliability of DC-SF cell can be achieved for MLC/TLC 256Gb/512Gb 3D NAND flash memories.
Esophageal Diverticulum Illustrated by Barium Swallow During Left Atrial Catheter Ablation for Atrial Fibrillation (2006)

L eft atrial radiofrequency catheter ablation guided by a 3-dimensional electroanatomic mapping system (CARTO, Biosense-Webster, Diamond Bar, Calif) was performed in a 67-year-old woman with paroxysmal atrial fibrillation. To avoid delivery of radiofrequency energy near the esophagus, the patient was asked to swallow 5 cm 3 of barium paste (E-Z-EM, Lake Success, NY) before conscious sedation, as described previously. 1 The esophagram delineated a previously undiagnosed esophageal diverticulum (Figure The location of the esophagus relative to the posterior wall of the left atrium was tagged on the electroanatomic map (Figure The diverticulum was 20 mm long and 17 mm wide.
Providing an Oxidizing Environment for the Cell-Free Expression of Disulfide-Containing Proteins by Exhausting the Reducing Activity of Escherichia coli S30 Extract (2006)

We developed a novel method of producing proteins containing multiple disulfide bonds in a cell-free protein synthesis system. To provide an optimized redox potential during the synthesis of truncated plasminogen activator (rPA), we pretreated the E. coli S30 extract with an excess amount of oxidized glutathione based on the anticipation that the reducing potential of the S30 extract would be exhausted through the reduction of the oxidized glutathione molecules. As expected, it was found that the reducing activity of the S30 extract was remarkably decreased through the pretreatment, and active rPA was produced when the pretreated S30 extract was used after removing the residual glutathione molecules. In particular, compared to the method involving the iodoacetamide treatment of S30 extract, the present protocol was effective in producing active rPA during the batch reaction of cell-free protein synthesis.
The age factor in Alzheimer’s disease (2015)

Alzheimer's disease is the most common type of dementia, and it is characterized by a decline in memory or other thinking skills. The greatest risk factor for Alzheimer's disease is advanced age. A recent genome-wide study identified a locus on chromosome 17 associated with the age at onset, and a specific variant in CCL11 is probably responsible for the association. The association of a protective haplotype with a 10-year delay in the onset of Alzheimer's disease and the identification of a CCL11 variant with possible functional roles in this association might allow the future development of immunomodulators with the potential to halve disease incidence.