gebhart/patrepeval huggingface dataset:
Structural Differences between the Woodchuck Hepatitis Virus Core Protein in the Dimer and Capsid States Are Consistent with Entropic and Conformational Regulation of Assembly (2019)

Hepadnaviruses are hepatotropic enveloped DNA viruses with an icosahedral capsid. Hepatitis B virus (HBV) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (WHV), an HBV homologue, has been an important model system for drug development. The dimeric capsid protein (Cp) has multiple functions during the viral life cycle and thus has become an important target for a new generation of antivirals. Purified HBV and WHV Cp spontaneously assemble into 120-dimer capsids. Though they have 65% identity, WHV Cp has error-prone assembly with stronger protein-protein association. We have taken advantage of the differences in assemblies to investigate the basis of assembly regulation. We determined the structures of the WHV capsid to 4.5-Å resolution by cryo-electron microscopy (cryo-EM) and of the WHV Cp dimer to 2.9-Å resolution by crystallography and examined the biophysical properties of the dimer. We found, in dimer, that the subdomain that makes protein-protein interactions is partially disordered and rotated 21° from its position in capsid. This subdomain is susceptible to proteolysis, consistent with local disorder. WHV assembly shows similar susceptibility to HBV antiviral molecules, suggesting that HBV assembly follows similar transitions. These data show that there is an entropic cost for assembly that is compensated for by the energetic gain of burying hydrophobic interprotein contacts. We propose a series of stages in assembly that incorporate a disorder-to-order transition and structural shifts. We suggest that a cascade of structural changes may be a common mechanism for regulating high-fidelity capsid assembly in HBV and other viruses.<b>IMPORTANCE</b> Virus capsids assemble spontaneously with surprisingly high fidelity. This requires strict geometry and a narrow range of association energies for these protein-protein interactions. It was hypothesized that requiring subunits to undergo a conformational change to become assembly active could regulate assembly by creating an energetic barrier and attenuating association. We found that woodchuck hepatitis virus capsid protein undergoes structural transitions between its dimeric and its 120-dimer capsid states. It is likely that the closely related hepatitis B virus capsid protein undergoes similar structural changes, which has implications for drug design. Regulation of assembly by structural transition may be a common mechanism for many viruses.
Microplate Modeling under Coupled Structural-Fluidic-Electrostatic Forces (2004)

We present a model for the dynamic behavior of microplates under the coupled e&ects of squeeze-film damping, electrostatic actuation, and mechanical forces. The model simulates the dynamics of microplates and predicts their quality factors under a wide range of gas pressures and applied electrostatic forces up to the pullin instability. The model utilizes the nonlinear EulerBernoulli beam equation, the linearized dynamic von
Penicillins from 3- and 5-phenylisothiazole-4-carboxylic acids and alkoxy derivatives (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPenicillins from 3- and 5-phenylisothiazole-4-carboxylic acids and alkoxy derivativesR. G. Micetich and R. RaapCite this: J. Med. Chem. 1968, 11, 1, 159–160Publication Date (Print):January 1, 1968Publication History Published online1 May 2002Published inissue 1 January 1968https://pubs.acs.org/doi/10.1021/jm00307a040https://doi.org/10.1021/jm00307a040research-articleACS PublicationsRequest reuse permissionsArticle Views65Altmetric-Citations13LEARN 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-Alertsclose Get e-Alerts
Simulation of a cochlear implant device diminishes the electrophysiological auditory orienting reaction to speech (2008)

Cochlear implants (CIs) have made remarkable progress to recover a large range of auditory functions after profound sensorineural hearing loss. The speech processor of an CI assimilates auditory input with different speech encoding strategies and has a strong impact on speech intelligibility. As prototyping new speech encoding strategies is time-consuming, the aim of our study was to evaluate an electrophysiological measure of auditory change detection in a virtual cochlear implant device for further preclinical testing of speech processing strategies in normal hearing subjects. Besides pitch discrimination we tested for automatic attentional orienting to speech sounds as CI users suffer from impaired attentional orienting to unexpected auditory changes (Nager et al., 2007). ERPs were recorded in 10 healthy subjects (passive and active listening). Natural sounds and virtual CI stimuli were presented via headphones using a modified oddball paradigm. A frequent standard (1000Hz, p=0.7) and rare deviant sounds were randomly presented (ISI 0.8–1.2s). Rare deviant tones consisted of three different frequencies (1200Hz, 1600Hz, 2200Hz, p=0.075, each). Furthermore, rare digitized phonemes (da, p=0.075) were presented to analyze auditory perception of natural speech sounds. Subjects were instructed to give a speeded response for each deviant (active condition) or to read a book (passive condition). Hitrates and RT were recorded. To develop an electrophysiological indicator of active discrimination abilities, the P3b ERP was calculated. Preattentive detection of auditory changes and automatic orienting were quantified by the mismatch negativity (MMN) and P3a ERPs (passive condition). Separate averages were obtained for natural and virtual sounds. These were generated by a matlab procedure to simulate a HiRes CI speech coding strategy. Active listening: hitrates for pitch deviants and speech sounds were significantly higher for natural sounds (88.2 vs. 72.1%; p<0.02). Whereas phonemes were easily detected in both experimental conditions (>96.7%) 1200Hz deviant detection was strikingly impaired in the HiRes condition (27.2 vs. 77.5%; p<0.001). P3b ERPs were lower for the 1200Hz deviants but did not differ between simulated and natural tones (p>0.5). Passive listening: MMN amplitudes were lower for „HiRes“ stimuli (p<0.02). For both, natural and simulated stimuli phonemes generated a larger MMN than frequency deviants (p<0.05). For natural stimuli phonemes only generated a significant orienting reaction (P3a). Interestingly, no orienting was triggered by phonemes or pitch deviants in the HiRes condition (stimulus x stimulation condition p<0.02). Simulation of a CI speech coding strategy in normal hearing subjects results in a largely degraded automatic orienting reaction to speech sounds although active detection of these speech sounds is not impaired. ERPs provide a detailed objective measure for future development of CI speech coding strategies.
NLRP3 inflammasome via IL-1β regulates PCSK9 secretion: Erratum (2021)

[This corrects the article DOI: 10.7150/thno.45939.].
Data from Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen-deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen-induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Androgen-induced DNA damage was assessed by comet assays and γH2A.X foci formation. Effects of androgen stimulation and radiation were determined &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; with xenograft models.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We document that androgen treatment of androgen-deprived prostate cancer cell lines resulted in a dose- and time-dependent induction of widespread DSBs. Generation of these breaks was dependent on androgen receptor and topoisomerase II beta but not on cell-cycle progression. &lt;i&gt;In vitro&lt;/i&gt; models demonstrated a synergistic interaction between IR and androgen stimulation when IR is given at a time point corresponding with high levels of androgen-induced DSB formation. Furthermore, &lt;i&gt;in vivo&lt;/i&gt; studies showed a significant improvement in tumor growth delay when radiation was given shortly after androgen repletion in castrated mice.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These results suggest a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. &lt;i&gt;Clin Cancer Res; 22(13); 3310–9. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Chua and Bristow, p. 3124&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Isolation and characterization of Nylanderia fulva virus 1, a positive-sense, single-stranded RNA virus infecting the tawny crazy ant, Nylanderia fulva (2016)

We report the discovery of Nylanderia fulva virus 1 (NfV-1), the first virus identified and characterized from the ant, Nylanderia fulva. The NfV-1 genome (GenBank accession KX024775) is 10,881 nucleotides in length, encoding one large open reading frame (ORF). Helicase, protease, RNA-dependent RNA polymerase, and jelly-roll capsid protein domains were recognized within the polyprotein. Phylogenetic analysis placed NfV-1 in an unclassified clade of viruses. Electron microscopic examination of negatively stained samples revealed particles with icosahedral symmetry with a diameter of 28.7±1.1nm. The virus was detected by RT-PCR in larval, pupal, worker and queen developmental stages. However, the replicative strand of NfV-1 was only detected in larvae. Vertical transmission did not appear to occur, but horizontal transmission was facile. The inter-colonial field prevalence of NfV-1 was 52±35% with some local infections reaching 100%. NfV-1 was not detected in limited samples of other Nylanderia species or closely related ant species.
Is there such a thing as a molecular organic alloy? (2019)

In inorganic materials, an alloy is a mixture of two or more substances that generally exhibits electronic and/or physical properties that differ from those of its constituents. No evidence for similar alloy properties is found for molecular organic solids.
Universal nanothin silk coatings via controlled spidroin self-assembly (2018)

Robust, biocompatible, and facile coatings are promising for improving the in vivo performance of medical implants and devices. Here, we demonstrate the formation of nanothin silk coatings by leveraging the biomimetic self-assembly of eADF4(C16), an amphiphilic recombinant protein based on the Araneus diadematus dragline spidroin ADF4. These coatings result from concurrent adsorption and supramolecular assembly of eADF4(C16) induced by KH2PO4, thereby providing a mild one-pot coating strategy in which the coating rate can be controlled by protein and KH2PO4 concentration. The thickness of the coatings ranges from 2-30 nm depending on the time immersed in the aqueous coating solution. Coatings can be formed on hydrophobic and hydrophilic substrates regardless of surface chemistry and without requiring specialized surface activation. Moreover, coatings appear to be stable through vigorous rinsing and prolonged agitation in water. Grazing incidence wide angle X-ray scattering, single-molecule force spectroscopy, and Congo red staining techniques confirm the formation of β-sheet nanocrystals within the eADF4(C16) coating, which contributes to the cohesive and adhesive stability of the material. Coatings are exceptionally smooth in the dry state and are hydrophilic regardless of substrate hydrophobicity. Under aqueous conditions, nanothin silk coatings exhibit the properties of a hydrogel material.
Novel Boundary Lubrication Mechanisms from Molecular Pillows of Lubricin Brush-Coated Graphene Oxide Nanosheets (2022)

There are numerous biomedical applications where the interfacial shearing of surfaces can cause wear and friction, which can lead to a variety of medical complications such as inflammation, irritation, and even bacterial infection. We introduce a novel nanomaterial additive comprised of two-dimensional graphene oxide nanosheets (2D-NSCs) coated with lubricin (LUB) to reduce the amount of tribological stress in biomedical settings, particularly at low shear rates where boundary lubrication dominates. LUB is a glycoprotein found in the articular joints of mammals and has recently been discovered as an ocular surface boundary lubricant. The ability of LUB to self-assemble into a "telechelic" brush layer on a variety of surfaces was exploited here to coat the top and bottom surfaces of the ultrathin 2D-NSCs in solution, effectively creating a biopolymer-coated nanosheet. A reduction in friction of almost an order of magnitude was measured at a bioinspired interface. This reduction was maintained after repeated washing (5×), suggesting that the large aspect ratio of the 2D-NSCs facilitates effective lubrication even at diluted concentrations. Importantly, and unlike LUB-only treatment, the lubrication effect can be eliminated over 15 rinsing cycles, suggesting that the LUB-coated 2D-NSCs do not exhibit any binding interactions with the shearing surfaces. The effective lubricating properties of the 2D-NSCs combined with full reversibility through rinsing make the LUB-coated 2D-NSCs an intriguing candidate as a lubricant for biomedical applications.
Flippase (FLP) recombinase-mediated marker recycling in the dermatophyte Arthroderma vanbreuseghemii (2014)

Biological processes can be elucidated by investigating complex networks of relevant factors and genes. However, this is not possible in species for which dominant selectable markers for genetic studies are unavailable. To overcome the limitation in selectable markers for the dermatophyte Arthroderma vanbreuseghemii (anamorph: Trichophyton mentagrophytes), we adapted the flippase (FLP) recombinase-recombination target (FRT) site-specific recombination system from the yeast Saccharomyces cerevisiae as a selectable marker recycling system for this fungus. Taking into account practical applicability, we designed FLP/FRT modules carrying two FRT sequences as well as the flp gene adapted to the pathogenic yeast Candida albicans (caflp) or a synthetic codon-optimized flp (avflp) gene with neomycin resistance (nptII) cassette for one-step marker excision. Both flp genes were under control of the Trichophyton rubrum copper-repressible promoter (PCTR4). Molecular analyses of resultant transformants showed that only the avflp-harbouring module was functional in A. vanbreuseghemii. Applying this system, we successfully produced the Ku80 recessive mutant strain devoid of any selectable markers. This strain was subsequently used as the recipient for sequential multiple disruptions of secreted metalloprotease (fungalysin) (MEP) or serine protease (SUB) genes, producing mutant strains with double MEP or triple SUB gene deletions. These results confirmed the feasibility of this system for broad-scale genetic manipulation of dermatophytes, advancing our understanding of functions and networks of individual genes in these fungi.
Recapitulating the frataxin activation mechanism in an engineered bacterial cysteine desulfurase supports the architectural switch model (2020)

ABSTRACT Iron-sulfur (Fe-S) clusters have a key role in many biochemical processes and are essential for most life forms. Despite recent mechanistic advances in understanding the Fe-S cluster biosynthetic pathway, critical questions remain unresolved. Although human NFS1 and E. coli IscS share ∼60% sequence identity, NFS1 exhibits low activity and requires activation by the Friedreich’s ataxia protein frataxin (FXN) for in vivo function. Surprisingly, structures of the human complex reveal three distinct quaternary structures with one form exhibiting the same subunit interactions as IscS. An architectural switch model has been proposed in which evolutionarily lost interactions between NFS1 subunits results in the formation of low-activity architectures; FXN binding compensates for these lost interactions and facilitates a subunit rearrangement to activate the complex. Here, we used a structure and evolution-guided approach to identify three conserved residues proposed to weaken interactions between NFS1 subunits and transplanted these amino acids into IscS. Compared to native IscS, the engineered variant had a 4000-fold weaker dimer interface and diminished activity that correlated with the absence of the second catalytic subunit. Remarkably, the addition of the FXN homolog to the engineered variant stimulated the decay of the Cys-quinonoid pyridoxal 5’-phosphate intermediate, shifted IscS from the monomeric to dimeric form, and increased the cysteine desulfurase activity, reproducing results from the human system and supporting the architectural switch model. Overall, these studies indicate a weakening of the homodimeric interface was a key development during the evolution of the eukaryotic system and provide new insights into the role of FXN.
Kir, a novel Ras-family G-protein, induces invasive pseudohyphal growth in Saccharomyces cerevisiae. (1995)

Kir belongs to a novel class of Ras-family G-proteins which includes Gem and Rad. These proteins are unique among Ras super-family G-proteins since their expression is under transcriptional regulation in mammalian cells. To gain insight into the function of Kir, we took advantage of the well-defined signal transduction pathways of yeast. When kir is expressed in Saccharomyces cerevisiae, the transformants form pseudohyphae and exhibit invasive properties characteristics of yeast cells undergoing a developmental transition induced by nitrogen starvation. Analysis of pseudohyphal signaling pathway mutants suggests that the Kir-induced pseudohyphae formation requires a MAP kinase cascade involving ste20, ste11, ste7 but not ste5 gene products. Furthermore, our results are consistent with the idea that Kir functions upstream of the STE20 kinase which plays a critical role in two distinct MAP kinase cascades.
Clairvoyant Networks (2019)

We use the term clairvoyant to refer to networks which provide on-demand visibility for any flow at any time. Traditionally, network visibility is achieved by instrumenting and passively monitoring all flows in a network. SDN networks, by design endowed with full visibility, offer another alternative to network-wide flow monitoring. Both approaches incur significant capital and operational costs to make networks clairvoyant. In this paper, we argue that we can make any existing network clairvoyant by installing one or more SDN-enabled switches and a specialized controller to support on-demand visibility. We analyze the benefits and costs of such clairvoyant networks and provide a basic design by integrating two existing mechanisms for updating paths through legacy switches with SDN, telekinesis and magnet MACs. Our evaluation on a lab testbed and through extensive simulations show that, even with a single SDN-enabled switch, operators can make any flow visible for monitoring within milliseconds, albeit at 38% average increase in path length. With as many as 2% strategically chosen legacy switches replaced with SDN switches, clairvoyant networks achieve on-demand flow visibility with negligible overhead.
Next generation passive optical network offering 40Gb/s or more bandwidth (2013)

This paper reviews PON technologies with a rate of at least 40 Gb/s for the next generation broadband access. The time and wavelength division multiplexed PON (TWDM-PON) is investigated as the primary solution for 40 Gb/s access.
Analysis of CD8 + T cell response during the 2013–2016 Ebola epidemic in West Africa (2018)

The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8<sup>+</sup> T cell responses. We investigated immune responses of individuals infected with Ebola virus (EBOV) during the 2013-2016 West Africa epidemic in Sierra Leone, where the majority of the >28,000 EBOV disease (EVD) cases occurred. We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8<sup>+</sup> T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8<sup>+</sup> T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8<sup>+</sup> T cells to EBOV VP24, VP35, and VP40 also made CD8<sup>+</sup> T cells to NP, but rarely to GP. We identified 34 CD8<sup>+</sup> T cell epitopes for Ebola. Our data indicate the immunodominance of the EBOV NP-specific T cell response and suggest that its inclusion in a vaccine along with the EBOV GP would best mimic survivor responses and help boost cell-mediated immunity during vaccination.
Servo-Pattern Design and Track-Following Control for Nanometer Head Positioning on Flexible Tape Media (2011)

Achieving multi-Terabyte capacity in tape cartridges requires a substantially higher track density than that available in present systems, and hence a significantly higher positioning accuracy is required of the track-following servo in tape drives. In this paper, advanced concepts are considered for several elements of a tape system that enhance the track-following servo performance to reach nanometer positioning accuracy. We introduce a novel method for optimizing the geometry of servo patterns in a timing-based servo system. The design criterion aims to minimize the measurement error in the position-error signal (PES) yielded by a digital synchronous servo channel. A flangeless tape path is adopted to mitigate high-frequency components of the lateral tape motion. The track-following servo controller, which is designed based on the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> approach, takes into account the measured plant transfer function, the disturbance characteristics of the tape path, and the properties of servo channel. These elements are combined to investigate the track-following performance achievable with a new high-SNR magnetic tape based on perpendicularly-oriented BaFe particles. With this setup, a record closed-loop track-following performance of less than 14 nm PES standard deviation is demonstrated.