gebhart/patrepeval huggingface dataset:
N-Terminal Extensions Retard Aβ42 Fibril Formation but Allow Cross-Seeding and Coaggregation with Aβ42 (2015)

Amyloid β-protein (Aβ) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the aggregation process. Until recently, naturally occurring amyloid β-protein (Aβ) variants were believed to begin at or after the canonical β-secretase cleavage site within the amyloid β-protein precursor. However, N-terminally extended forms of Aβ (NTE-Aβ) were recently discovered and may contribute to Alzheimer's disease. Here, we have used thioflavin T fluorescence to study the aggregation kinetics of Aβ42 variants with N-terminal extensions of 5-40 residues, and transmission electron microscopy to analyze the end states. We find that all variants form amyloid fibrils of similar morphology as Aβ42, but the half-time of aggregation (t1/2) increases exponentially with extension length. Monte Carlo simulations of model peptides suggest that the retardation is due to an underlying general physicochemical effect involving reduced frequency of productive molecular encounters. Indeed, global kinetic analyses reveal that NTE-Aβ42s form fibrils via the same mechanism as Aβ42, but all microscopic rate constants (primary and secondary nucleation, elongation) are reduced for the N-terminally extended variants. Still, Aβ42 and NTE-Aβ42 coaggregate to form mixed fibrils and fibrils of either Aβ42 or NTE-Aβ42 catalyze aggregation of all monomers. NTE-Aβ42 monomers display reduced aggregation rate with all kinds of seeds implying that extended termini interfere with the ability of monomers to nucleate or elongate. Cross-seeding or coaggregation may therefore represent an important contribution in the in vivo formation of assemblies believed to be important in disease.
Hyperstable Collagen Based on 4-Fluoroproline Residues (2007)

Collagen is the most abundant protein in animals. The conformational stability of the collagen triple helix is enhanced by the hydroxyl group of its prevalent (2S,4R)-4-hydroxyproline residues. For >30 years, the prevailing paradigm had been that this enhanced stability is due to hydrogen bonds mediated by bridging water molecules. We have tested this hypothesis with synthetic collagen triple helices containing (2S)-4-fluoroproline residues. The results have unveiled a wealth of stereoelectronic effects that contribute markedly to the stability of collagen (as well as other proteins). This new understanding is leading to hyperstable synthetic collagens for a variety of applications in biotechnology and biomedicine.
Endhost-based shortest path routing in dynamic networks: An online learning approach (2013)

We consider the problem of endhost-based shortest path routing in a network with unknown, time-varying link qualities. Endhost-based routing is needed when internal nodes of the network do not have the scope or capability to provide globally optimal paths to given source-destination pairs, as can be the case in networks consisting of autonomous subnetworks or those with endhost-based routing restrictions. Assuming the source can probe links along selected paths, we formulate the problem as an online learning problem, where an existing solution achieves a performance loss (called regret) that is logarithmic in time with respect to (wrt) an offline algorithm that knows the link qualities. Current solutions assume coupled probing and routing; in contrast, we give a simple algorithm based on decoupled probing and routing, whose regret is only constant in time. We then extend our solution to support multi-path probing and cooperative learning between multiple sources, where we show an inversely proportional decay in regret wrt the probing rate. We also show that without the decoupling, the regret grows at least logarithmically in time, thus establishing decoupling as critical for obtaining constant regret. Although our analysis assumes certain conditions (i.i.d.) on link qualities, our solution applies with straightforward amendments to much broader scenarios where these conditions are relaxed. The efficacy of the proposed solution is verified by trace-driven simulations.
Very low permittivity slot-fed dielectric resonator antennas with improved bandwidth for millimetre-wave applications (2009)

This paper introduces a simple method to increase the bandwidth of slot-fed dielectric resonator antennas (DRAs) for millimetre-wave applications. Bandwidth augmentation is achieved by decreasing the dielectric constant of DRAs while the critical coupling is obtained by properly adjusting the slot size and position. Two numerical methods, based on finite element method and finite integral technique, are used to verify the approach. A 10-dB impedance bandwidth of 27 percent is attained for DRAs with dielectric constant as low as 4 while the radiation properties remain similar to those of higher dielectric constant DRAs.
GREEN(ER) STEELMAKING WITH THE MIDREX ® DIRECT REDUCTION PROCESS (2007)

Worldwide, there is an increasing emphasis on environmental issues. In the area of gaseous emissions, the Kyoto Protocol has put great pressure on the industrialized countries. Under the Protocol, those countries pledged to reduce their collective emissions of “greenhouse gases” by five percent compared to 1990 levels. When compared to the emissions expected with normal economic growth, the level represents a 29 percent cut. There are six gases of interest, with carbon dioxide (CO2) the most significant. The agreement came into force on February 16, 2005. Almost all industrialized nations have ratified the agreement, except the United States and Australia.
Mutated MYD88 Activates the BCR Component SYK and Provides a Rationale Therapeutic Target in Waldenstrom's Macroglobulinemia (2017)

Abstract Background: Mutations in the Toll receptor (TLR) pathway are highly prevalent in Waldenstrom's Macroglobulinemia (WM) and ABC DLBCL, wherein mutated MYD88 triggers NF-kB pro-survival signaling through BTK/IRAK. Activation of B-cell receptor (BCR) signaling can also be triggered by activating mutations in CD79A/B in ABC DLBCL, though are rare in WM (5-8%). Despite these findings, there is evidence for BCR activation in WM (Argyropoulos et al, Leukemia 2016). We hypothesized that crosstalk between TLR and BCR might account for aberrant BCR signaling in WM. We therefore performed PhosFLow studies on MYD88 and BCR signaling components and observed the hyperactivation of SYK (pY525-pY526) in MYD88 mutated WM (BCWM.1, MWCL-1) cells compared to wild-type MYD88 expressing control cells. We next treated MYD88 mutated WM cells with a peptide inhibitor of MYD88 homodimerization, and observed that the phosphorylation of SYK at tyrosine 525 and 526 (pY525-pY526) together with phosphorylation of BTK at tyrosine 223 (pY223) was markedly reduced. In contrast, the MYD88 inhibitor had no impact on either SYK or BTK activation in MYD88 wild-type Ramos cells. Knockdown of MYD88 by lentiviral transduction in MYD88 mutated BCWM.1 cells confirmed the reduction of SYK (pY525-pY526) by two shRNAs. Cell viability analysis by CellTiter-Glo® assay showed that the SYK inhibitor R406 was cytotoxic to MYD88 mutated WM cells at pharmacologically attainable drug levels (EC50 0.247 uM for BCWM.1; 0.315 uM for MWCL-1), versus >1 uM for MYD88 wild-type control cells. Furthermore, the combination of R406 with ibrutinib produced synergistic cytotoxicity in MYD88 mutated WM cells. Conclusion: Our findings demonstrate that in addition to TLR path activation, mutated MYD88 activates the BCR component SYK tyrosine kinase. These findings provide the rationale for combined therapeutic targeting of BCR and TLR pathways in MYD88 mutated WM. Disclosures Castillo: Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Millennium: Research Funding; Abbvie: Research Funding. Treon: Pharmacyclics: Consultancy, Research Funding.
P4‐028: Accelerated Aging and Metabolic Disruption in the Brain Provide the Basis for Alzheimer's Disease Progression Modeling (2010)

Alzheimer's disease (AD) is a complex neurological disorder both similar and distinct from the process of normal aging. Understanding the sequence of the dramatic changes in human brain associated with the disease requires systems biology perspective. We profiled 3 brain regions from more than 600 individuals collected by Harvard Brain Tissue Resource Center and applied statistical learning methods to identify the sequence of changes associated with normal aging and those induced by AD. Our approach was based on supervised metagene (signature) discovery followed by signature score assessment. We analyzed prefrontal cortex samples from non-demented and AD subsets and showed that they share the same first principal component. This gene expression pattern is significantly associated with chronological age in non-demented individuals. In AD subjects, regardless of actual chronological age at time of death, the pattern approaches extreme levels not expected before the age of 120. This biological Aging signature is the dominant pattern reproducibly detected in normal and AD brains across different brain regions, responsible for as much as 35% of transcriptional variance in this dataset. We also identified several novel AD-specific signatures based on significant differential expression between AD and normal brains with matching Aging levels. These signatures represent a constellation of biological events specific to disease processes induced at different stages of disease progression, with their levels measured by the signature scores. Genes associated with brain inflammation and metabolic disruption exhibited remarkably similar expression across brain regions for the same individual, demonstrated the systemic nature of these perturbations. Other processes including lipid metabolism were more region-specific. Analysis of relationships between different signatures across the dataset allowed us to model the sequence of biological events during AD progression. This work laid out a framework for understanding the interplay between aging and AD, and for development of AD specific signatures. As demonstrated in another presentation by our group, this framework is useful to assess animal models of AD and to study genetic drivers for different aspects of the disease.
A Rationally Designed Aldolase Foldamer (2008)

Neatly folded: A decameric β-peptide shows enzyme-like catalytic properties. The foldamer, which bears a terminal heptanoyl unit and displays a thermostable helical structure with an array of ammonium-group side chains, accelerates a retroaldol reaction (see scheme) by more than three orders of magnitude through an imine mechanism.
Artificial Intelligence-Aided Low Cost and Flexible Graphene Oxide-Based Paper Sensor for Ultraviolet and Sunlight Monitoring (2022)

The adverse effect of ultraviolet (UV) radiation on human beings has sparked intense interest in the development of new sensors to effectively monitor UV and solar exposure. This paper describes a novel low-cost and flexible graphene oxide (GO)-based paper sensor capable of detecting the total amount of UV or sun energy delivered per unit area. GO is incorporated into the structure of standard printing paper, cellulose, via a low-cost fabrication technique. The effect of UV and solar radiation exposure on the GO paper-based sensor is investigated using a simple color change analysis. As a result, users can easily determine the amount of ultraviolet or solar energy received by the sensor using a simple color analysis application. A neural network (ANN) model is also explored to learn the relation between UV color intensity and exposure time, then digitally display the results. The accuracy for the developed ANN reached 96.83%. The disposable, cost-effective, simple, biodegradable, safe, and flexible characteristics of the paper-based UV sensor make it an attractive candidate for a variety of sensing applications. This work provides new vision toward developing highly efficient and fully disposable GO-based photosensors.
Therapeutic Efficacy of Human Hepatocyte Transplantation in a SCID/uPA Mouse Model with Inducible Liver Disease (2010)

Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes. Functional support by engrafted HH may be secured by strategies aimed at limiting this bystander effect.
Flexible Margin Kinematics and Vortex Formation of Aurelia aurita and Robojelly (2014)

The development of a rowing jellyfish biomimetic robot termed as "Robojelly", has led to the discovery of a passive flexible flap located between the flexion point and bell margin on the Aurelia aurita. A comparative analysis of biomimetic robots showed that the presence of a passive flexible flap results in a significant increase in the swimming performance. In this work we further investigate this concept by developing varying flap geometries and comparing their kinematics with A. aurita. It was shown that the animal flap kinematics can be replicated with high fidelity using a passive structure and a flap with curved and tapered geometry gave the most biomimetic performance. A method for identifying the flap location was established by utilizing the bell curvature and the variation of curvature as a function of time. Flaps of constant cross-section and varying lengths were incorporated on the Robojelly to conduct a systematic study of the starting vortex circulation. Circulation was quantified using velocity field measurements obtained from planar Time Resolved Digital Particle Image Velocimetry (TRDPIV). The starting vortex circulation was scaled using a varying orifice model and a pitching panel model. The varying orifice model which has been traditionally considered as the better representation of jellyfish propulsion did not appear to capture the scaling of the starting vortex. In contrast, the pitching panel representation appeared to better scale the governing flow physics and revealed a strong dependence on the flap kinematics and geometry. The results suggest that an alternative description should be considered for rowing jellyfish propulsion, using a pitching panel method instead of the traditional varying orifice model. Finally, the results show the importance of incorporating the entire bell geometry as a function of time in modeling rowing jellyfish propulsion.
PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer (2017)

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance <i>in vitro</i> and <i>in vivo</i> Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. <i>Cancer Res; 77(17); 4613-25. ©2017 AACR</i>.
Semi-supervised classification for dynamic Android malware detection (2017)

A growing number of threats to Android phones creates challenges for malware detection. Manually labeling the samples into benign or different malicious families requires tremendous human efforts, while it is comparably easy and cheap to obtain a large amount of unlabeled APKs from various sources. Moreover, the fast-paced evolution of Android malware continuously generates derivative malware families. These families often contain new signatures, which can escape detection when using static analysis. These practical challenges can also cause traditional supervised machine learning algorithms to degrade in performance. In this paper, we propose a framework that uses model-based semi-supervised (MBSS) classification scheme on the dynamic Android API call logs. The semi-supervised approach efficiently uses the labeled and unlabeled APKs to estimate a finite mixture model of Gaussian distributions via conditional expectation-maximization and efficiently detects malwares during out-of-sample testing. We compare MBSS with the popular malware detection classifiers such as support vector machine (SVM), $k$-nearest neighbor (kNN) and linear discriminant analysis (LDA). Under the ideal classification setting, MBSS has competitive performance with 98\% accuracy and very low false positive rate for in-sample classification. For out-of-sample testing, the out-of-sample test data exhibit similar behavior of retrieving phone information and sending to the network, compared with in-sample training set. When this similarity is strong, MBSS and SVM with linear kernel maintain 90\% detection rate while $k$NN and LDA suffer great performance degradation. When this similarity is slightly weaker, all classifiers degrade in performance, but MBSS still performs significantly better than other classifiers.
‘Protecting the Public, Securing the Profession’: Enforcing Ethical Standards among Software Engineers (1997)

The public interest should be a central ethical concern of members of the computer profession, and this would also result in the social status and power of software engineers being augmented. One attractive means to encourage and enforce ethical standards on the part of engineers and employers would be a system of licensing by internationally recognised professional bodies whose legitimacy stems from their capacity to act in the public interest. The author is Senior Lecturer in the Department of Computer Science, School of Applied Sciences, Anglia Polytechnic University, East Road, Cambridge CB1 1PT, England; email jwilkes@bridge.anglia.ac.uk or 10016.3425@compuserve.com
Re: Bacterial Virulence Phenotypes of Escherichia coli and Host Susceptibility Determine Risk for Urinary Tract Infections (2018)

No AccessJournal of UrologyUrological Survey1 Jun 2018Re: Bacterial Virulence Phenotypes of Escherichia coli and Host Susceptibility Determine Risk for Urinary Tract Infections Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.03.011AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Bacterial Virulence Phenotypes of Escherichia coli and Host Susceptibility Determine Risk for Urinary Tract Infections." The Journal of Urology, 199(6), pp. 1399–1400 © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 199Issue 6June 2018Page: 1399-1400 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
Alternatively spliced isoform of P-selectin is present in vivo as a soluble molecule. (1994)

To demonstrate the presence of a soluble isoform of P-selectin predicted from cDNA sequencing (Johnston, G.I., Bliss, G.A., Newman, P.J., and McEver, R.P. (1990) J. Biol. Chem. 265, 21381-21385), we immunoisolated and compared structurally P-selectin from fresh frozen human plasma with that from washed intact platelets. Plasma P-selectin was reactive with rabbit antiserum to a synthesized peptide (residues 762-774 of mature P-selectin) but was significantly less reactive with antibody to a peptide (residues 747-760). In contrast, platelet P-selectin reacted with both antibodies. S-Pyridylethylated plasma P-selectin was fractionated by reversed phase-high performance liquid chromatography into two major species. From platelets, two virtually identical species were separated. Sequential digestion with Achromobacter protease I and then Staphylococcus V8 protease produced peptides assigned to the tail region of the protein including the putative spliced site. From the more hydrophilic species in both plasma and platelets, a peptide completely lacking the sequence of the putative spliced site was identified. In contrast, the more hydrophobic species yielded a peptide with an intact transmembrane sequence. Hence, these results provide direct evidence that the previously predicted soluble isoform of P-selectin is actually synthesized in vivo and is present as a circulating molecule.
A Hybrid Scheme of Public-Key Encryption and Somewhat Homomorphic Encryption (2015)

We introduce a hybrid homomorphic encryption that combines public-key encryption (PKE) and somewhat homomorphic encryption (SHE) to reduce the storage requirements of most somewhat or fully homomorphic encryption (FHE) applications. In this model, messages are encrypted with a PKE and computations on encrypted data are carried out using SHE or FHE after homomorphic decryption. To obtain efficient homomorphic decryption, our hybrid scheme combines IND-CPA PKE without complicated message padding with SHE with a large integer message space. Furthermore, if the underlying PKE is multiplicative, the proposed scheme has the advantage that polynomials of arbitrary degree can be evaluated without bootstrapping. We construct this scheme by concatenating the ElGamal and Goldwasser-Micali schemes over a ring ℤ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</sub> for a composite integer N whose message space is ℤ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">×</sup> . To accelerate the homomorphic evaluation of the PKE decryption, we introduce a method to reduce the degree of the exponentiation circuit at the cost of additional public keys. Using the same technique, we present an efficient partial solution to an open problem which is to evaluate mod q mod p arithmetic homomorphically for large p. As an independent interest, we also obtain a generic method for converting from private-key SHE to public-key SHE. Unlike the method described by Rothblum, we are free to choose the SHE message space.
ChemInform Abstract: Benzoxazolamines and Benzothiazolamines: Potent, Enantioselective Inhibitors of Leukotriene Biosynthesis with a Novel Mechanism of Action. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.