gebhart/patrepeval huggingface dataset:
Cellular localization of D‐lactate dehydrogenase and NADH oxidase from Archaeoglobus fulgidus (2002)

Members of the genus Archaeoglobus are hyperthermophilic sulfate reducers with an optimal growth temperature of 83 degrees C. Archaeoglobus fulgidus can utilize simple compounds including D-lactate, L-lactate and pyruvate as the sole substrate for carbon and electrons for dissimilatory sulfate reduction. Previously we showed that this organism makes a D-lactate dehydrogenase (Dld) that requires FAD and Zn2+ for activity. To determine the cellular location and topology of Dld and to identify proteins that interact with Dld, an antibody directed against Dld was prepared. Immunocytochemical studies using gold particle-coated secondary antibodies show that more than 85% of Dld is associated with the membrane. A truncated form of Dld was detected in immunoblots of whole cells treated with protease, showing that Dld is an integral membrane protein and that a significant portion of Dld, including part of the FAD-binding pocket, is outside the membrane facing the S-layer. The gene encoding Dld is part of an operon that includes noxA2, which encodes one of several NADH oxidases in A. fulgidus. Previous studies have shown that NoxA2 remains bound to Dld during purification. Thin sections of A. fulgidus probed simultaneously with antibodies against Dld and NoxA2 show that both proteins co-localized to the same sites in the membrane. Although these data show a tight interaction between NoxA2 and Dld, the role of NoxA2 in electron transport reactions is unknown. Rather, NoxA2 may protect proteins involved in electron transfer by reducing O2 to H2O2 or H2O.
RNA-Tethered Phenyl Azide Photocrosslinking via a Short-Lived Indiscriminant Electrophile (2003)

Arylazide mediated photocrosslinking has been widely used to obtain structural constraints in biological systems, even though the reactive species generated upon photolysis in aqueous solution have not been well characterized. We establish a mechanistic framework for formation of adducts between photoactivated 3-hydroxyphenyl azide and RNA. Tethered to an internal site in an RNA duplex via a 2'-amido linkage, photolysis of the aryl azide yields a cross-strand cross-link. Analysis of the ability of reagents with diagnostic reactivities to intercept formation of this cross-strand cross-link supports the assignment that the photoactivated intermediate is the ketenimine or a ketenimine-derived ring expansion product. Neither the initially produced singlet nitrene nor the subsequently formed triplet nitrene contribute to cross-link formation. Argon matrix and time-resolved solution experiments show that photolysis of free 3-hydroxyphenyl azide releases (in <or=20 ns) either a ketenimine or azepinone intermediate that reacts with nucleophiles. Adenosine, uridine, and guanosine monophosphate nucleotides have approximately equivalent abilities to quench the cross-strand cross-link, indicating that the photoactivated intermediate reacts broadly with functional groups in RNA. The reactive intermediate forms an adduct with adenosine monophosphate when tethered to both an RNA duplex or unstructured single strand; thus, cross-link formation is independent of the local RNA environment. The lifetime of the reactive intermediate generated upon photolysis of free 3-hydroxyphenyl azide in 50 mM Hepes diamine buffer is found to be 60-160 micros or significantly shorter than large scale RNA folding events. RNA-tethered 3-hydroxyphenyl azide cross-linking in aqueous buffer can thus be used with confidence to map structural neighbors, including most dynamic interactions, in RNA.
Design and Application of Variable Temperature Setup for Scanning Electron Microscopy in Gases and Liquids at Ambient Conditions (2015)

Scanning electron microscopy (SEM) of nanoscale objects in dry and fully hydrated conditions at different temperatures is of critical importance in revealing details of their interactions with an ambient environment. Currently available WETSEM capsules are equipped with thin electron-transparent membranes and allow imaging of samples at atmospheric pressure, but do not provide temperature control over the sample. Here, we developed and tested a thermoelectric cooling/heating setup for WETSEM capsules to allow ambient pressure in situ SEM studies with a temperature range between -15 and 100°C in gaseous, liquid, and frozen conditions. The design of the setup also allows for correlation of the SEM with optical microscopy and spectroscopy. As a demonstration of the possibilities of the developed approach, we performed real-time in situ microscopy studies of water condensation on a surface of Morpho sulkowskyi butterfly wing scales. We observed that initial water nucleation takes place on top of the scale ridges. These results confirmed earlier discovery of a preexisting polarity gradient of the ridges of Morpho butterflies. Our developed thermoelectric cooling/heating setup for environmental capsules meets the diverse needs for in situ nanocharacterization in material science, catalysis, microelectronics, chemistry, and biology.
Polymyxin-B Hemoperfusion and Endotoxin Removal: Lessons from a Review of the Literature (2010)

Sepsis involves a complex interaction between bacterial toxins and the host immune system. Endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis producing proinflammatory cytokines and activating the complement system, and is thus an ideal potential therapeutic target. Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-F) has been shown to bind and neutralize endotoxin in both in vitro and in vivo studies. Therefore, this extracorporeal therapy with PMX-F can potentially interrupt the biological cascade of sepsis. A systematic review of the published literature found positive effects of PMX-F on blood pressure and dopamine/dobutamine use, the PaO(2)/FiO(2) ratio, endotoxin removal, and mortality. It should be noted, however, that many of the analyzed studies were of suboptimal quality, which may then exaggerate the magnitude of these effects. Since this meta-analysis, other studies have been published including a multicenter randomized controlled trial on abdominal septic shock. In this study, PMX-F, when added to conventional therapy, significantly improved hemodynamics and organ dysfunction, and reduced 28-day mortality in this targeted population. There is clear biological rationale for endotoxin removal in the clinical management of severe sepsis and septic shock. The current literature seems to provide some support for this premise, and provides the basis for further rigorous study.
Universally composable adaptive oblivious transfer (with access control) from standard assumptions (2013)

In this paper, we provide the first scheme that realises an attribute-based access control system for static resources that offers maximal privacy and is secure in the universal composability framework (UC). More precisely, we offer a protocol for adaptive oblivious transfer, where the sender can enforce an attribute-based access control policy for each record and nevertheless learns neither which record a user retrieves nor which attributes a user has. As additional results we provide a new structure-preserving signature scheme from the SXDH assumption and a new universally composable adaptive oblivious transfer protocol that is secure under two DDH-like assumptions and is the most efficient one secure under ``non $q$-type'' assumptions. We believe the new signature scheme to be of independent interest as a building block that is compatible with Groth-Sahai non-interactive zero-knowledge proofs.
A Neural Architecture for Designing Truthful and Efficient Auctions (2019)

Auctions are protocols to allocate goods to buyers who have preferences over them, and collect payments in return. Economists have invested significant effort in designing auction rules that result in allocations of the goods that are desirable for the group as a whole. However, for settings where participants' valuations of the items on sale are their private information, the rules of the auction must deter buyers from misreporting their preferences, so as to maximize their own utility, since misreported preferences hinder the ability for the auctioneer to allocate goods to those who want them most. Manual auction design has yielded excellent mechanisms for specific settings, but requires significant effort when tackling new domains. We propose a deep learning based approach to automatically design auctions in a wide variety of domains, shifting the design work from human to machine. We assume that participants' valuations for the items for sale are independently sampled from an unknown but fixed distribution. Our system receives a data-set consisting of such valuation samples, and outputs an auction rule encoding the desired incentive structure. We focus on producing truthful and efficient auctions that minimize the economic burden on participants. We evaluate the auctions designed by our framework on well-studied domains, such as multi-unit and combinatorial auctions, showing that they outperform known auction designs in terms of the economic burden placed on participants.
Antiglucocorticoids, Neurogenesis and Depression (2009)

Recent evidence suggests that antiglucocorticoids, like conventional antidepressants, may recover depressive symptoms by boosting hippocampal neurogenesis. Here, we explore several possible antiglucocorticoid-based antidepressive therapeutic strategies. Firstly, we review specific glucocorticoid receptor/antagonist interactions. Secondly, we discuss a potential new therapeutic target, doublecortin-like kinase, which regulates glucocorticoid signaling in neuronal progenitor cells.
A Novel Biological Role for Peptidyl-Arginine Deiminases: Citrullination of Cathelicidin LL-37 Controls the Immunostimulatory Potential of Cell-Free DNA (2018)

LL-37, the only human cathelicidin that is released during inflammation, is a potent regulator of immune responses by facilitating delivery of oligonucleotides to intracellular TLR-9, thereby enhancing the response of human plasmacytoid dendritic cells (pDCs) to extracellular DNA. Although important for pathogen recognition, this mechanism may facilitate development of autoimmune diseases. In this article, we show that citrullination of LL-37 by peptidyl-arginine deiminases (PADs) hindered peptide-dependent DNA uptake and sensing by pDCs. In contrast, carbamylation of the peptide (homocitrullination of Lys residues) had no effect. The efficiency of LL-37 binding to oligonucleotides and activation of pDCs was found to be inversely proportional to the number of citrullinated residues in the peptide. Similarly, preincubation of carbamylated LL-37 with PAD2 abrogated the peptide's ability to bind DNA. Conversely, LL-37 with Arg residues substituted by homoarginine, which cannot be deiminated, elicited full activity of native LL-37 regardless of PAD2 treatment. Taken together, the data showed that citrullination abolished LL-37 ability to bind DNA and altered the immunomodulatory function of the peptide. Both activities were dependent on the proper distribution of guanidinium side chains in the native peptide sequence. Moreover, our data suggest that cathelicidin/LL-37 is citrullinated by PADs during NET formation, thus affecting the inflammatory potential of NETs. Together this may represent a novel mechanism for preventing the breakdown of immunotolerance, which is dependent on the response of APCs to self-molecules (including cell-free DNA); overactivation may facilitate development of autoimmunity.
Evaluation of a Pseudo‐Elastic Model for the Mullins Effect (2004)

Abstract Typically, the stress‐strain response in filled rubbers depends strongly on the maximum loading previously encountered. The phenomenon, known as the Mullins effect, can be idealized for many purposes as an instantaneous and irreversible softening of the stress‐strain curve that occurs whenever the load increases beyond its prior all‐time maximum value. At times when the load is less than a prior maximum, nonlinear elastic behavior prevails. Ogden and Roxburgh proposed an empirical model capable of describing this phenomenon, based on a pseudo‐elastic concept. Their model, with minor adaptations, has recently been implemented in a commercial finite element program. This paper demonstrates the effectiveness of the implemented model for several benchmark cases including uniform hydrostatic loading, simple tension, pure shear, and equibiaxial tension. The paper also compares model predictions with experimental results for a series of experiments conducted with various combinations of axial tension/compression and torsion loading.
SU-FF-T-530: Volumetric Arc Treatment of Multiple Brain Metastases (2009)

Purpose: To assess the feasibility of treating a patient with multiple brain metastases using volumetric modulated arc therapy (VMAT). Method and Materials: We calculate dose to a patient with two brain metastases (one in the right occipital lobe and one in the right cerebellum) using a single, 356° dynamic arc with the SmartArc feature in Pinnacle's treatment planning system (Philips, Inc.). The MRI-based gross tumor volumes were expanded isotropically by 3mm and combined to make a single planning target volume. The prescribed dose was 18Gy in 1 fraction, normalized to 80% of the point dose at isocenter. The VMAT plan was compared to a Gamma Knife (GK) plan with a prescription of 18Gy in 1 fraction, normalized to 50% of maximum dose for each lesion with no expansion and to an 8-field IMRT plan with coplanar and non-coplanar static beams with the same prescription as the VMAT plan. Results: Satisfactory coverage was obtained for all plans with a Dmin of 19.8Gy, 17.1Gy and 19.6Gy to the GTV for the VMAT, GK and IMRT, respectively. The conformality index for the VMAT, GK and IMRT plan were 1.28, 1.93 and 1.29, respectively. The volume of normal brain tissue receiving 12Gy for the VMAT, GK and IMRT plans were 8.4, 1.0 and 7.9 cc, respectively. A benefit of the VMAT plan is that it may be delivered in 6.6mins, compared to the GK plan which could take up to 1.5hours. Conclusion: The VMAT dose distribution for a multiple brain metastases patient was equivalent to a conventional IMRT plan. Compared to GK plans, the VMAT plan is more conformal but delivers higher dose to normal brain tissue due to larger margins. We are performing an evaluation of the necessary margin based on setup data at our institution and looking at patients with >2 metastases.
Efficient Method for Site-Specific 18F-Labeling of Biomolecules Using the Rapid Condensation Reaction between 2-Cyanobenzothiazole and Cysteine (2012)

An efficient method based on a rapid condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine has been developed for (18)F-labeling of N-terminal cysteine-bearing peptides and proteins. An (18)F-labeled dimeric cRGD ([(18)F]CBTRGD(2)) has been synthesized with an excellent radiochemical yield (92% based on radio-HPLC conversion, 80% decay-corrected, and isolated yield) and radiochemical purity (>99%) under mild conditions using (18)F-CBT, and shown good in vivo tumor targeting efficiency for PET imaging. The labeling strategy was also applied to the site-specific (18)F-labeling of a protein, Renilla lucifierase (RLuc8) with a cysteine residue at its N-terminus. The protein labeling was achieved with 12% of decay-corrected radiochemical yield and more than 99% radiochemical purity. This strategy should provide a general approach for efficient and site-specific (18)F-labeling of various peptides and proteins for in vivo molecular imaging applications.
Multiparametric Magnetic Resonance Imaging for Active Surveillance of Prostate Cancer (2017)

Active surveillance has gained popularity as an acceptable management option for men with low-risk prostate cancer. Successful utilization of this strategy can delay or prevent unnecessary interventions - thereby reducing morbidity associated with overtreatment. The usefulness of active surveillance primarily depends on correct identification of patients with low-risk disease. However, current population-wide algorithms and tools do not adequately exclude high-risk disease, thereby limiting the confidence of clinicians and patients to go on active surveillance. Novel imaging tools such as mpMRI provide information about the size and location of potential cancers enabling more informed treatment decisions. The term "multiparametric" in prostate mpMRI refers to the summation of several MRI series into one examination whose initial goal is to identify potential clinically-significant lesions suitable for targeted biopsy. The main advantages of MRI are its superior anatomic resolution and the lack of ionizing radiation. Recently, the Prostate Imaging-Reporting and Data System has been instituted as an international standard for unifying mpMRI results. The imaging sequences in mpMRI defined by Prostate Imaging Reporting and Data System version 2 includes: T2-weighted MRI, diffusion-weighted MRI, derived apparent-diffusion coefficient from diffusion-weighted MRI, and dynamic contrast-enhanced MRI. The use of mpMRI prior to starting active surveillance could prevent those with missed, high-grade lesions from going on active surveillance, and reassure those with minimal disease who may be hesitant to take part in active surveillance. Although larger validation studies are still necessary, preliminary results suggest mpMRI has a role in selecting patients for active surveillance. Less certain is the role of mpMRI in monitoring patients on active surveillance, as data on this will take a long time to mature. The biggest obstacles to routine use of prostate MRI are quality control, cost, reproducibility, and access. Nevertheless, there is great a potential for mpMRI to improve outcomes and quality of treatment. The major roles of MRI will continue to expand and its emerging use in standard of care approaches becomes more clearly defined and supported by increasing levels of data.
Reply to Vilar et al. : Sleep or hide, better for survival anytime (2008)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Tailor-Made Nanocontainers for Combined Magnetic-Field-Induced Release and MRI (2014)

The synthesis of a novel nanocapsule-based carrier system is described, possessing a triggered release in remote-controlled fashion upon application of an external magnetic field in combination with the possibility to use the capsules as contrast agents for magnetic resonance imaging (MRI). Therefore, polymeric nanocontainers containing a high amount of superparamagnetic MnFe2 O4 nanoparticles and a thermo-degradable shell are fabricated via a miniemulsion route. The process allows the facile encapsulation of hydrophilic compounds, as demonstrated for a model dye. Release of the encapsulated dye is achieved upon application of an external alternating magnetic field. While the magnetic nanoparticles here act as heat generators to stimulate the decomposition of the shell and subsequently a release of the payload, they additionally enable the use of the nanocapsules as imaging agents for MRI. Due to the encapsulated magnetic nanoparticles, the nanocapsules possess high r2 relaxivity values of 96-120 Hz mmol(-1) , which makes them suitable for MRI. In toxicity experiments, the nanocapsules show no cell toxicity up to fairly high concentrations (600 µg mL(-1) ). Due to their dual-functionality, the nanocapsules possess high potential as nanocarriers with combined magnetic-field-induced release capability and as contrast agents for MRI.
Novel and compact open-ended CRLH-TL notch filter (2016)

A novel and very small metamaterial notch filter below 900 MHz is proposed in this paper. In the UHF band, compared to the size of the open-ended quarter-wavelength stub that is, 0.25 λg (42 mm), the length of the proposed filter is 0.07 λg (12 mm) approximately five times smaller. The notch filter is realized by a very short 90°-phase shifter of the CRLH structure with one-end open-terminated. The design method is explained theoretically, while the circuit and geometry are simulated and validated through EM simulations and fabrication. The measured results show a high degree of agreement with the simulated results. The results illustrate the notch created at 900 MHz by the filter to avoid the conflict with Z-wave communication, UHF RFID tag and uplink of GSM-E. © 2016 Wiley Periodicals, Inc. Int J RF and Microwave CAE 26:247–253, 2016.
The Year In G Protein-Coupled Receptor Research (2009)

I (R.P.M.) presented "The Year In G Protein-Coupled Receptor Research" at ENDO 2009. I first described the diversity of ligands and the five families into which the approximately 800 G protein-coupled receptors (GPCRs) are grouped, their basic structural architectures, their preeminent role in signaling, and the enormous scope for developing drugs targeted at GPCRs. I then spoke about some of the exciting breakthroughs in solving the atomic level structures of the active state of rhodopsin, beta(2)-adrenergic, beta(1)-adrenergic, and A(2A)-adenosine receptors. I also described studies on the structural changes accompanying the activation of the rhodopsin family of GPCRs. From these recent technical advances, we can anticipate that many more GPCR structures will emerge, which will afford us greater insight into their common and unique structural features and, particularly, the mechanisms underlying their activation. These insights will guide us in our understanding of how GPCRs operate, both in the normal and pathological situation. Although these crystal structures are highly informative, it is important to recognize that they represent static frozen conformations of a single GPCR state. New biophysical techniques are therefore being utilized to facilitate the dynamic monitoring of GPCR structural changes in relation to ligand activation. Solving of the crystal structures of GPCRs has also presented the real possibility of using the information of the ligand-binding pocket to allow in silico screening for novel small-molecule ligands. I then reviewed the concept of ligand-induced selective signaling of GPCRs, which is opening up new insights into more selective drug development. The assembly of GPCRs as homo- and heterooligomers and their phosphorylation and association with a vast array of trafficking and signal-modulating proteins are emerging as major mechanisms underlying the functioning of GPCRs. Differential expression and recruitment of these proteins provide a mechanism for subtle physiological regulation of cellular activity. Finally, I mentioned some of the GPCRs that have lately come to the fore as novel regulators in endocrinology. These included fatty acid-specific GPCRs expressed in pancreatic beta-cells and novel neuroendocrine GPCRs regulating reproduction.
The Media Gateway Control Protocol (MGCP) Bulk Audit Package (2003)

This document is being published for the information of the community. It describes a non-IETF protocol that is currently being deployed in a number of products. Implementers should be aware of RFC 3015, which was developed in the IETF Megaco Working Group and the ITU-T SG16, and which is considered by the IETF and the ITU-T to be the standards-based (including reviewed security considerations) way to meet the needs that MGCP was designed to address.
ChemInform Abstract: Molecular Recognition‐Controlled Membrane Disruption by a Bis(crown ether) Bola‐Amphiphile. (1997)

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.