gebhart/patrepeval huggingface dataset:
Mechanism of Allosteric Inhibition of the Enzyme IspD by Three Different Classes of Ligands (2017)

Enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are attractive targets for the development of herbicides and drugs against infectious diseases. While this pathway is essential for many pathogens and plants, mammals do not depend on it for the synthesis of isoprenoids. IspD, the third enzyme of the nonmevalonate pathway, is unique in that it has an allosteric regulatory site. We elucidated the binding mode of phenylisoxazoles, a new class of allosteric inhibitors. Allosteric inhibition is effected by large conformational changes of a loop region proximal to the active site. We investigated the different roles of residues in this loop by mutation studies and identified repulsive interactions with Asp291 and Asp292 to be responsible for inhibition. Crystallographic data and the response of mutant enzymes to three different classes of allosteric inhibitors provide an in-depth understanding of the allosteric mechanism. The obtained mutant enzymes show selective resistance to allosteric inhibitors and provide conceptually valuable information for future engineering of herbicide-resistant crops. We found that the isoprenoid precursors IPP and DMAPP are natural inhibitors of Arabidopsis thaliana IspD; however, they do not seem to bind to the allosteric site.
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8 (2017)

Interferon exposure boosts cell-autonomous immunity for more efficient pathogen control. But how interferon-enhanced immunity protects the cytosol against bacteria and how professionally cytosol-dwelling bacteria avoid clearance are insufficiently understood. Here we demonstrate that the interferon-induced GTPase family of guanylate-binding proteins (GBPs) coats Shigella flexneri in a hierarchical manner reliant on GBP1. GBPs inhibit actin-dependent motility and cell-to-cell spread of bacteria but are antagonized by IpaH9.8, a bacterial ubiquitin ligase secreted into the host cytosol. IpaH9.8 ubiquitylates GBP1, GBP2, and GBP4 to cause the proteasome-dependent destruction of existing GBP coats. This ubiquitin coating of Shigella favors the pathogen as it liberates bacteria from GBP encapsulation to resume actin-mediated motility and cell-to-cell spread. We conclude that an important function of GBP recruitment to S. flexneri is to prevent the spread of infection to neighboring cells while IpaH9.8 helps bacterial propagation by counteracting GBP-dependent cell-autonomous immunity.
Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6 (2023)

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (30kb). Here, we designed a plasmid-based viral genome assembly and resc ue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.
Representation of reuse mechanisms for digital work with multiple right-holders (2002)

The management of contents with cleared rights is becoming important on the Internet. There may be multiple rights holders for one copyrighted work in those cases in which multiple creators exist and/or those cases in which the reuse of existing works is carried out. In this paper, a conceptual model is designed on the basis of the examination of the dependency of each piece of information which is necessary in those cases where multiple rights holders have the rights to one particular work in a transaction system. A language for the description of rights information, named CMF (Copyright Management Framework), is designed based on this model, and the design and development of a sample implementation of a CMF interpreter are carried out.
Teaching Crowdsourcing: An Experience Report (2018)

Crowdsourcing is the process of accomplishing a task by using a typically open call to invite members of the public (the “crowd”) to work on one's task. The authors describe a project assignment in which students received the opportunity of practicing crowdsourcing to accomplish a hummed song recognition task, yielding improved comprehension of the concept and high student satisfaction.
High-Speed Imaging Meets Single-Cell Analysis (2018)

The Bigger PictureSingle-cell analysis is the study of individual biological cells among populations for identifying cell-to-cell differences and elucidating cellular heterogeneity invisible to population-averaged measurements. It is important for cancer biology, immunology, microbiology, and stem cell biology. In recent years, high-speed imaging has been shown to be highly effective for large-scale single-cell analysis by virtue of its ability to acquire information-rich images at a high frame rate to obtain a snapshot library of numerous cells in a short duration of time (with one cell per frame). Here, we review several emerging high-speed imaging methods and their emerging utility to large-scale single-cell analysis.SummaryHigh-speed imaging is an indispensable tool in today's scientific research, industry, and energy because it enables blur-free observation and monitoring of fast transient dynamics. It is commonly used for various applications, including sports, manufacturing, and fusion science, in which slow-motion analysis is conducted to elucidate their dynamics. On the other hand, the past several years have seen another and radically new application of high-speed imaging, namely single-cell analysis—the study of individual biological cells among populations for identifying cell-to-cell differences and elucidating cellular heterogeneity invisible to population-averaged measurements. This exciting application has been made possible by exploiting high-speed imaging's capability of acquiring information-rich images at high frame rates to provide a snapshot library of numerous cells in a short duration of time (with one cell per frame). In this article, we review the principles of several unique high-speed imaging methods for microscopy and their emerging application to large-scale single-cell analysis.Graphical abstract
On-Chip Quantum Communication Devices (2022)

We present here results of the Quantum Technology Flagship project UNIQORN in the area of integrated photonics for quantum communication applications. Three distinct integration platforms, namely indium phosphide based monolithic integration, polymer-based hybrid integration and the CMOS-compatible silicon platform, have been employed to manufacture components and sub-systems on chip for quantum communication devices. The choice of different platforms was made to exploit the best characteristics of each platform for the intended quantum communication device. The indium phosphide platform was employed to manufacture a transmitter chip for quantum key distribution featuring laser, modulators, and attenuators. The transmitter chip was evaluated in a QKD experiment achieving a secure rate of 1 kbit/s. The polymer platform was investigated for engineering non-classical light sources. Entangled and heralded single-photon sources, based on non-linear optics, were assembled on the polymer in a hybrid fashion together with waveguides and other passive micro-optical elements. A quantum random number generator, featuring a 70% randomness extraction efficiency, was also fabricated using the polymer integration technique. An array of 32 individual single-photon avalanche diodes, operating at room temperature and featuring an onboard coincidence logic, was coupled to the chip to demonstrate direct detection of photons on the polymer. Finally, a transimpedance amplifier based on gallium arsenide high electron mobility transistors was produced with an exceptional large electrical noise clearance of 28 dB at 100 MHz.
An auxilliary grid method for the calculation of electrostatic terms in density functional theory on a real-space grid (2015)

In this work we show the implementation of a linear scaling algorithm for the calculation of the Poisson integral. We use domain decomposition and non-uniform auxiliary grids (NGs) to calculate the electrostatic interaction. We demonstrate the approach within the PARSEC density functional theory code and perform calculations of long 1D carbon chains and other long molecules. Finally, we discuss possible applications to additional problems and geometries.
p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction (2001)

The neuronal cyclin-dependent kinase p35/cdk5 comprises a catalytic subunit (cdk5) and an activator subunit (p35). To identify novel p35/cdk5 substrates, we utilized the yeast two-hybrid system to screen for human p35 binding partners. From one such screen, we identified beta -catenin as an interacting protein. Confirmation that p35 binds to beta -catenin was obtained by using glutathione S-transferase (GST)-beta -catenin fusion proteins that interacted with both endogenous and transfected p35, and by showing that beta -catenin was present in p35 immunoprecipitates. p35 and beta -catenin also displayed overlapping subcellular distribution patterns in cells including neurons. Finally, we demonstrated that p35/cdk5 phosphorylates beta -catenin. beta -catenin also binds to presenilin-1 and altered beta -catenin/presenilin-1 interactions may be mechanistic in Alzheimer's disease (AD). Abnormal p35/cdk5 activity has also been suggested to contribute to AD. We therefore investigated how modulation of p35/cdk5 activity influenced beta -catenin/presenilin-1 interactions. Inhibition of p35/cdk5 with roscovitine did not alter the steady state levels of either beta -catenin or presenilin-1 but reduced the amount of presenilin-1 bound to beta -catenin. Thus, p35/cdk5 binds and phosphorylates beta -catenin and regulates its binding to presenilin-1. The findings reported here therefore provide a novel molecular framework to connect p35/cdk5 with beta -catenin and presenilin-1 in AD.
Utilization rate of multi carrier transponders deployed in the CONUS network with MCS-based contentionless OXCs (2015)

In the context of Nyquist superchannels transmission in the CONUS WDM network, this study illustrates the compromise between saving add/drop equipments in contentionless OXCs and improving utilization rate of the whole capacity of the deployed integrated multi carrier transponders.
Antieancer Agent Development, 3. X-ray Structure of Dimethyl 1-Methoxy- (1989)

C25H26010 , M r = 486.48, monoclinic, P2Jn, a = 13.708 (6), b= 11.755 (4), c= 15.491 (5) A, fl= 108-92 (3) °, V = 2361.3 A 3, Z = 4, Dx = 1.37 g cm -3, a(MoKa) = 0.71073 A, /z = 0.66 cm-1, F(000) = 1024, T = 293 K, final R = 0.051 for 1884 observed (Fo>_5o(Fo)) reflections. The 3-methoxycarbonyl group and the 4-aryl ring occupy quasiaxial positions in the observed structure. There is no crystallo- graphically imposed symmetry. Several intermolec- ular van der Waals interactions of note occur in this compound.
Concurrent engineering approach to design of assembly lines (2000)

info:eu-repo/semantics/published
Original Article Hyperbaric spinal anesthesia with ropivacaine coadministered with sufentanil for cesarean delivery: a dose-response study (2015)

* Equal contributors. Received December 20, 2014; Accepted March 16, 2015; Epub April 15, 2015; Published April 30, 2015 Abstract: Adjuvant sufentanil could achieve effective spinal anesthesia with low dose of hyperbaric ropivacaine for cesarean delivery. Two previous studies had calculated the 50% effective dose (ED50) of intrathecal ropivacaine coadministered with sufentanil for cesarean delivery. However, the 95% effective dose (ED95) of intrathecal hyper- baric ropivacaine coadministered with sufentanil for cesarean delivery remains uncertain. This study determined the ED95 of intrathecal hyperbaric ropivacaine coadministered with sufentanil for cesarean delivery. 80 ASA physi- cal status I or II parturients undergoing elective cesarean delivery were enrolled in this prospective, randomized, double-blind investigation. A combined spinal and epidural anesthesia was performed at the L3-L4 interspace. Patients received a dose of spinal ropivacaine coadministered with sufentanil 5 μg diluted to 3.0 ml with normal saline and 0.5 ml of 10% dextrose: 7.5 mg (n = 20), 9.0 mg (n = 20), 10.5 mg (n = 20), or 12 mg (n = 20). An ef- fective dose was defined as a dose that provided bilateral sensory block to T7 within 10 min after intrathecal drug administration and required no epidural top-up for surgery to be completed. The ED50 and ED95 values for suc- cessful anesthesia were determined using a logistic regression model. The ED50 (95% confidence interval (CI)) for successful anesthesia was 8.4 (4.0-9.8) mg and the ED95 (95% CI) was 11.4 (9.7-13.9) mg. The results show that the ED95 of intrathecal hyperbaric ropivacaine coadministered with sufentanil 5 μg for cesarean delivery was 11.4 mg. The addition of sufentanil could significantly reduce the dosage of ropivacaine.
Practical and Analytical Studies in Powertrain and Vehicle Refinement (1995)

&lt;div class="htmlview paragraph"&gt;The successful application of noise source identification and reduction techniques, by timely and cost-effective integration of practical and analytical methods, can be demonstrated by case studies. The general areas under consideration include:&lt;/div&gt; &lt;div class="htmlview paragraph"&gt; &lt;ul class="list disc"&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Noise sources generated within the engine&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Noise radiation from the engine surfaces&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;Vehicle interior and exterior noise&lt;/div&gt; &lt;/li&gt; &lt;/ul&gt; &lt;/div&gt;
BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival (2019)

Malignant melanoma is one of the most difficult cancers to treat due to its resistance to chemotherapy. Despite recent successes with BRAF inhibitors and immune checkpoint inhibitors, many patients do not respond or become resistant to these drugs. Hence, alternative treatments are still required. Due to the importance of the BCL-2-regulated apoptosis pathway in cancer development and drug resistance, it is of interest to establish which proteins are most important for melanoma cell survival, though the outcomes of previous studies have been conflicting. To conclusively address this question, we tested a panel of established and early passage patient-derived cell lines against several BH3-mimetic drugs designed to target individual or subsets of pro-survival BCL-2 proteins, alone and in combination, in both 2D and 3D cell cultures. None of the drugs demonstrated significant activity as single agents, though combinations targeting MCL-1 plus BCL-XL, and to a lesser extent BCL-2, showed considerable synergistic killing activity that was elicited via both BAX and BAK. Genetic deletion of BFL-1 in cell lines that express it at relatively high levels only had minor impact on BH3-mimetic drug sensitivity, suggesting it is not a critical pro-survival protein in melanoma. Combinations of MCL-1 inhibitors with BRAF inhibitors also caused only minimal additional melanoma cell killing over each drug alone, whilst combinations with the proteasome inhibitor bortezomib was more effective in multiple cell lines. Our data show for the first time that therapies targeting specific combinations of BCL-2 pro-survival proteins, namely MCL-1 plus BCL-XL and MCL-1 plus BCL-2, could have significant benefit for the treatment of melanoma.
Four-dimensional observation of ductile fracture in sintered iron using synchrotron X-ray laminography (2019)

Synchrotron X-ray laminography was used to examine the time-dependent evolution of the three-dimensional (3D) morphology of micropores in sintered iron during the tensile test. 3D snapshots showed that the networked open pores grow wider than 20 µm along the tensile direction, resulting in the internal necking of the specimen. Subsequently, these pores initiated the cracks perpendicular to the tensile direction by coalescing with the surrounding pre-existing microvoids or with the secondary-generated voids immediately before fracture. Topological analysis of the barycentric positions of these microvoids showed that they form the two-dimensional networks within the ∼20 µm of radius area. These observations strongly indicate that the microvoid coalescence could occur on shear planes formed close to the enlarged open pores or between closed pores by strain accumulation and play an important role in the crack initiation.
#4606 INNOVATIVE METHOD TO EVALUATE MATURATION OF NEWLY CREATED ARTERIO-VENOUS FISTULAS: INSIGHTS FROM A QUALITY IMPROVEMENT PROJECT (2023)

Abstract Background and Aims Recently, we introduced central-venous oxygen saturation (ScvO2) and estimated upper-body blood flow (eUBBF) to monitor the maturation of newly created arterio-venous fistulas (AVF) in hemodialysis (HD) patients [1]. The approach was implemented in a clinical quality improvement project (QIP). Method The QIP involved two Renal Research Institute dialysis centers in New York City that use the Crit-Line monitor (CLM, Fresenius Medical Care, Waltham, MA, USA) as part of the standard of care. CLM measures automatically and non-invasively hematocrit and oxygen saturation (i.e., ScvO2 in patients with central venous catheter as vascular access). eUBBF was computed as described previously [1]. Patients with a with a newly created AVF were included, irrespective of their HD vintage. The QIP team comprised a registered nurse per clinic, two research physicians, and two data analysts. The team met weekly to assess the AVF maturation progress based on eUBBF and ScvO2 data that were displayed on a specific dashboard. Successful AVF maturation is typically accompanied by a rise in cardiac output and eUBBF that starts immediately after AVF creation. However, it is unknown what degree of eUBBF increase indicates a subsequently successful AVF maturation. To identify predictive eUBBF thresholds, we correlated eUBBF changes with the progress of AVF maturation in the six weeks following AVF creation. We defined maturation as unsuccessful when the newly created AVF required an intervention (e.g., angioplasty) or was abandoned. Results We studied 39 patients (age 56 ±18 years; 25 males). Twenty-eight of them were incident patients. Two patients had a second AVF created. In 15 patients AVF maturation was unsuccessful. In these patients, eUBBF increased to an average of 119.2% (SD 35.2) compared to pre-AFV creation. In patients with successful AFV maturation (N = 24), eUBBF increased to an average of 153.7% (SD 31.6) (Figure 1). The difference between the groups is 34.4 percentage points (95% CI: 12.4 to 56.4; p = 0.003). Using eUBBF as a diagnostic measure to discriminate successful vs. failed AVF maturation, an area under the receiver operating characteristics curve of 0.824 (95% CI: 0.673 to 0.925; p&amp;lt;0.0001) was obtained. An eUBBF increase of 25% had a sensitivity of 59% and a specificity of 92% to predict AVF maturation outcomes. Conclusion Computation of eUBBF provides a simple and non-invasive means to track AVF maturation and predict its outcomes.
A new RNA polymerase sigma factor, σF is required for the late stages of morphological differentiation in Streptomyces spp. (1995)

A gene (sigF) encoding a new sigma factor was isolated from Streptomyces aureofaciens using a degenerate oligonucleotide probe designed from the GLI(KDNE)A motif lying within the well-conserved region 2.2 of the eubacterial sigma 70 family. Homologues were present in other Streptomyces spp., and that of the genetically well studied Streptomyces coelicolor A3(2) was also cloned. The nucleotide sequences of the two sigF genes were determined and shown to encode primary translation products of 287 (S. coelicolor) and 295 (S. aureofaciens) amino acid residues, both showing greatest similarity to sigma B of Bacillus subtilis. However, while sigma B is involved in stationary-phase gene expression and in the general stress response in B. subtilis, sigma F affects morphological differentiation in Streptomyces. Disruption of sigF did not affect vegetative growth but did cause a whi mutant phenotype. Microscopic examination showed that the sigF mutant produced spores that were smaller and deformed compared with those of the wild type, that the spore walls were thinner and sensitive to detergents and that in sigF mutant spores the chromosome failed to condense. sigma F is proposed to control the late stages of spore development in Streptomyces.
ChemInform Abstract: Nucleation Process in the Cavity of a 48‐Tungstophosphate Wheel Resulting in a 16‐Metal‐Center Iron Oxide Nanocluster. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck (2019)

Combinatorial treatment with adavosertib and alisertib leads to synergistic antitumor effects in <i>in vitro</i> and <i>in vivo</i> HNSCC models. These findings suggest a novel rational combination, providing a promising therapeutic avenue for <i>TP53-</i>mutated cancers.
A Case for Usage Tracking to Relate Digital Objects (2008)

This paper covers the evolution of the concept of Usage Tracking to automatically link digital objects such as documents. Extensive ethnographic studies of information work have revealed that establishing and maintaining relationships – between documents, between artifacts and between people – is at the core of information work. Focusing on just one aspect of this challenge, we looked for practical ways of relating digital documents. Leveraging the fieldwork, we designed a mechanism that captures the user’s activity across documents and reinterprets it as links between these documents. We implemented the mechanism as a running prototype to assess the feasibility of the concept, and in general gauge the opportunities to make better use of usage data – which are mostly gets ignored in today’s computing platforms. Object to object relation building through usage data has three important advantages over most existing methods for automatically establishing relations: first, it is behaviorist, not relying on guesswork about the user’s intentions; second, it is media agnostic: text, images and sounds are all just objects and treated alike; it is the user’s handling of the objects that matter, and third, it is application agnostic: it does not rely on privileged access to specific applications. 1