gebhart/patrepeval huggingface dataset:
Reversibly locking a protein fold in an active conformation with a disulfide bond: Integrin αL I domains with high affinity and antagonist activity<i>in vivo</i> (2001)

The integrin alphaLbeta2 has three different domains in its headpiece that have been suggested to either bind ligand or to regulate ligand binding. One of these, the inserted or I domain, has a fold similar to that of small G proteins. The I domain of the alphaM and alpha2 subunits has been crystallized in both open and closed conformations; however, the alphaL I domain has been crystallized in only the closed conformation. We hypothesized that the alphaL domain also would have an open conformation, and that this would be the ligand binding conformation. Therefore, we introduced pairs of cysteine residues to form disulfides that would lock the alphaL I domain in either the open or closed conformation. Locking the I domain open resulted in a 9,000-fold increase in affinity to intercellular adhesion molecule-1 (ICAM-1), which was reversed by disulfide reduction. By contrast, the affinity of the locked closed conformer was similar to wild type. Binding completely depended on Mg(2+). Orders of affinity were ICAM-1 > ICAM-2 > ICAM-3. The k(on), k(off), and K(D) values for the locked open I domain were within 1.5-fold of values previously determined for the alphaLbeta2 complex, showing that the I domain is sufficient for full affinity binding to ICAM-1. The locked open I domain antagonized alphaLbeta2-dependent adhesion in vitro, lymphocyte homing in vivo, and firm adhesion but not rolling on high endothelial venules. The ability to reversibly lock a protein fold in an active conformation with dramatically increased affinity opens vistas in therapeutics and proteomics.
Gene family encoding the major toxins of lethal <i>Amanita</i> mushrooms (2007)

Amatoxins, the lethal constituents of poisonous mushrooms in the genus Amanita, are bicyclic octapeptides. Two genes in A. bisporigera, AMA1 and PHA1, directly encode alpha-amanitin, an amatoxin, and the related bicyclic heptapeptide phallacidin, a phallotoxin, indicating that these compounds are synthesized on ribosomes and not by nonribosomal peptide synthetases. alpha-Amanitin and phallacidin are synthesized as proproteins of 35 and 34 amino acids, respectively, from which they are predicted to be cleaved by a prolyl oligopeptidase. AMA1 and PHA1 are present in other toxic species of Amanita section Phalloidae but are absent from nontoxic species in other sections. The genomes of A. bisporigera and A. phalloides contain multiple sequences related to AMA1 and PHA1. The predicted protein products of this family of genes are characterized by a hypervariable "toxin" region capable of encoding a wide variety of peptides of 7-10 amino acids flanked by conserved sequences. Our results suggest that these fungi have a broad capacity to synthesize cyclic peptides on ribosomes.
Morphology and electro-optical properties of reverse mode polymer dispersed liquid crystals (2000)

We have investigated the morphology and electro-optical properties of reverse mode polymer dispersed liquid crystals as a function of liquid crystal loading. Reverse mode shutters have been obtained by a polymerization-induced phase separation of mixtures, consisting of a liquid crystalline monomer and a non-reactive nematic liquid crystal, placed between rough conductive surfaces. Such surfaces are able to keep the photopolymerizable mixtures homeotropically aligned without the use of any aligning polymer substrate. OFF state transmittances are always larger than 80% and the switching fields decrease if the non-reactive liquid crystal percentage is increased. Both rise and decay times are always lower than 10 ms. The electro-optical properties have been related to the sample morphology and a simple mode is proposed.
Particle-Based Microarrays of Oligonucleotides and Oligopeptides (2014)

In this review, we describe different methods of microarray fabrication based on the use of micro-particles/-beads and point out future tendencies in the development of particle-based arrays. First, we consider oligonucleotide bead arrays, where each bead is a carrier of one specific sequence of oligonucleotides. This bead-based array approach, appearing in the late 1990s, enabled high-throughput oligonucleotide analysis and had a large impact on genome research. Furthermore, we consider particle-based peptide array fabrication using combinatorial chemistry. In this approach, particles can directly participate in both the synthesis and the transfer of synthesized combinatorial molecules to a substrate. Subsequently, we describe in more detail the synthesis of peptide arrays with amino acid polymer particles, which imbed the amino acids inside their polymer matrix. By heating these particles, the polymer matrix is transformed into a highly viscous gel, and thereby, imbedded monomers are allowed to participate in the coupling reaction. Finally, we focus on combinatorial laser fusing of particles for the synthesis of high-density peptide arrays. This method combines the advantages of particles and combinatorial lithographic approaches.
Advances in Gene Therapy for Hemophilia (2017)

Gene therapy provides hope for a cure for patients with hemophilia by establishing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene copy to replace the hemophilic patient's own defective gene. Hemophilia may be considered a "low-hanging fruit" for gene therapy because a small increment in blood factor levels (≥2% of normal) significantly improves the bleeding tendency from severe to moderate, eliminating most spontaneous bleeds. After decades of research, the first trial to provide clear evidence of efficiency after gene transfer in patients with hemophilia B using adeno-associated virus vectors was reported by the authors' group in 2011. This has been followed by unprecedented activity in this area, with the commencement of seven new early-phase trials involving >55 patients with hemophilia A or hemophilia B. These studies have, in large part, generated promising clinical data that lay a strong foundation for gene therapy to move forward rapidly to market authorization. This review discusses the data from the authors' studies and emerging results from other gene therapy trials in both hemophilia A and B.
Processing and enhanced piezoelectric properties of highly oriented compositionally modified Pb(Zr,Ti)O<sub>3</sub>ceramics fabricated by magnetic alignment (2015)

Highly oriented compositionally modified Pb(Zr,Ti)O3 (PZT) ceramics were successfully obtained by slip casting in a high magnetic field. PZT is a well-known superior ceramic with the highest piezoelectric properties, and these properties have been expected to be further improved through crystalline orientation. However, highly oriented PZT ceramics fabricated by slip casting in a high magnetic field have never been reported. We obtained oriented ceramics using compositionally modified PZT with Pb(Ni,Nb)O3, and their Lotgering factor was 0.77. The electromechanical coupling coefficient (k31) increased by 30%, and an extremely high value of 0.44 was achieved for the oriented ceramics.
Covalent binding of poly(ethylene glycol) (PEG) to the surface of red blood cells inhibits aggregation and reduces low shear blood viscosity (1997)

A simple method to coat human red blood cells (RBC) with PEG is described. Using a reactive derivative, monomethoxy-PEG (mPEG) was covalently attached to the surface of RBC in aqueous media under mild conditions. The PEG coating dramatically reduced aggregation and low shear viscosity of RBC resuspended in autologous plasma, and inhibited RBC agglutination by blood group-specific antibodies. Morphology and deformability of the PEG-treated cells were unaltered. The PEG coating of the RBC surface may be of significant benefit in the treatment of a variety of diseases characterized by vasoocclusion or impaired blood flow, e.g., myocardial infarction, sickle cell disease.
Use of coupling agents for internally reinforced rayon fibers (1992)

Two difunctional, sterically hindered compounds, 1,4-bis(3-aminopropyldimethylsilyl)-benzene and fumaric acid, were evaluated as possible coupling agents for composite skin-core textile fibers. Other silane coupling agents and surface treatments had been tried previously. The fibers were formed using a process similar to wire coating in which a commercially produced nylon 66 monofilament core fiber, pretreated with coupling agent, contacted a viscose rayon solution in the die. Subsequently, the coated fiber was passed through a sulfuric acid coagulation bath, water wash, and dryer. The coupling agent concentration and coating line speed were evaluated for their effect on enhancement of adhesion. The composite fibers were stitched into a carrier fabric which was subsequently abraded in an Accelerotor to test the effect of the variables on adhesion of the skin to the core. Certain combinations of line speed, concentration, and type of coupling agent were found to provide significant enhancement of adhesion compared with control fibers formed without the use of either coupling agent.
Features of the NIH atlas small animal PET scanner and its use with a coaxial small animal volume CT scanner (2003)

ATLAS (Advanced Technology Laboratory Animal Scanner), a small animal PET scanner designed to image animals the size of rats and mice, is about to enter service on the NIH campus in Bethesda, Maryland. This system is the first small animal PET scanner with a depth-of-interaction capability and the first to use iterative resolution recovery algorithms, rather than conventional filtered back projection, for "production" image reconstruction. ATLAS is also proximate to, and co-axial with, a high resolution small animal CT scanner. When fully integrated, spatially registered PET and CT images of each animal will be used to correct the emission data for radiation attenuation and to aid in target identification. In this report we describe some of the technical and functional features of this system and illustrate how these features are used in an actual small animal imaging study.
Abstract 4555: Selection of CD3 affinity allows generation of T-cell redirecting bispecific antibodies with unique pharmacokinetic and biodistribution properties (2020)

Abstract T-cell redirecting bispecific antibodies are an emerging class of therapeutic agents designed to simultaneously bind to T cells (via CD3) and tumor cell specific antigens (TSA), with the goal of inducing T cell-mediated killing of tumor cells. Despite promising pre-clinical and clinical efficacy from TSAxCD3 antibodies, these agents have associated toxicities that remain challenging. Here we present findings from a series of bispecific antibodies that were engineered to have a range of CD3 affinities, but which retained the same binding affinity to the selected tumor antigen. These agents were tested for killing of tumor cells in vitro, and for biodistribution, serum half-life, and anti-tumor activity in vivo. By altering the binding strength for CD3, bispecifics were generated that maintained potent killing of TSA+ cells but displayed differential profiles of cytokine release, pharmacokinetics, and biodistribution. Our results suggest that tuning CD3 affinity is a promising method to improve the therapeutic window of T cell-engaging bispecific antibodies. Citation Format: Lauric Haber, Kara Olson, Robert Babb, Marcus Kelly, Alison Crawford, Marc Retter, David DiLillo, Erica Ullman, Jennifer Finney, Lauren Canova, Arpita Pawashe, Danica Chiu, Kristin Vazzana, Priyanka Ram, Katja Mohrs, Amanda Dorvilliers, Jenny Xiao, Sosina Makonnen, Carlos Hickey, Cody Arnold, Jason Giurleo, Supriya Patel, Richard Tavare, Ya Ping Chen, Gang Chen, William Olson, Gavin Thurston, John Chia-Yang Lin, Aynur Hermann, Jessica Kirshner, Eric J. Smith. Selection of CD3 affinity allows generation of T-cell redirecting bispecific antibodies with unique pharmacokinetic and biodistribution properties [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4555.
Thermoelectric Properties of n-type ZrNiPb-Based Half-Heuslers (2017)

Here we investigate the half-Heusler ZrNiPb as a n-type thermoelectric material. Our results show that the n-type ZrNiPb-based materials can achieve high peak power factors, ∼50 μW cm–1 K–2, by optimally tuning the carrier concentration via Bi doping. By further Sn-alloying in Pb site, we achieve a significant reduction of lattice thermal conductivity while maintaining the power factor almost unchanged and hence noticeably improve the ZT. Our work demonstrates that n-type ZrNiPb-based half-Heuslers are promising thermoelectric materials.
A 2D Conditional Random Fields Model for Web Information Extraction (2005)

The Web contains an abundance of useful semi-structured information about real world objects, and our empirical study shows that strong sequence characteristics exist for the Web information about the objects of the same type across different Web sites. This paper introduces a two dimensional Conditional Random Fields model, incorporating the sequence characteristics and the 2D neighborhood dependencies, to automatically extract object information from the Web. We also present the experimental results comparing our model with the linear-chain CRF model in the domain of product information extraction. The experimental results show that our model significantly outperforms existing CRF models.
Dynamic surface grasping with directional adhesion (2013)

Dynamic surface grasping is applicable to landing of micro air vehicles (MAVs) and to grappling objects in space. In both applications, the grasper must absorb the kinetic energy of a moving object and provide secure attachment to a surface using, for example, gecko-inspired directional adhesives. Functional principles of dynamic surface grasping are presented, and two prototype grasper designs are discussed. Computer simulation and physical testing confirms the expected relationships concerning (i) the alignment of the grasper at initial contact, (ii) the absorption of energy during collision and rebound, and (iii) the force limits of synthetic directional adhesives.
MPEG-4 IPMP Extension for Interoperable Protection of Multimedia Content (2004)

To ensure secure content delivery, the Motion Picture Experts Group (MPEG) has dedicated significant effort to the digital rights management (DRM) issues. MPEG is now moving from defining only hooks to proprietary systems (e.g., in MPEG-2, MPEG-4 Version 1) to specifying a more encompassing standard in intellectual property management and protection (IPMP). MPEG feels that this is necessary in order to achieve MPEG's most important goal: interoperability. The design of the IPMP Extension framework also considers the complexity of the MPEG-4 standard and the diversity of its applications. This architecture leaves the details of the design of IPMP tools in the hands of applications developers, while ensuring the maximum flexibility and security. This paper first briefly describes the background of the development of the MPEG-4 IPMP Extension. It then presents an overview of the MPEG-4 IPMP Extension, including its architecture, the flexible protection signaling, and the secure messaging framework for the communication between the terminal and the tools. Two sample usage scenarios are also provided to illustrate how an MPEG-4 IPMP Extension compliant system works.
J024056 Template pattern matching for tibia and fibula using X-ray images and voxel model (2013)

The technique to estimate three-dimensional position and posture to elucidate the mechanism of a joint in the knees is effective. As one of the technique, the Template Pattern Matching (TPM) method based on 3D bone data is known. A prepared library based on 3D bone data is necessary for the TPM method. Our final goal is to alter the library,3D bone data constructed from simple X-rays image. In this study, proposed method were adapted to tibia and fibula. Tibia and fibula bone model comprised of voxel are prepared. Tibia and fibula bone model are transformed based on X-rays image respectively. When bone models were transformed, there was often a gap between two models. The two models were connected by new voxels. As the result posture estimate precision was θx=1.50 ± 1.29 deg, θy=0.98 ± 0.95 deg. Posture estimate precision of the conventional method with CT data was θx=l.05 ± 1.05 deg, θy=0.25 ± 0.51 deg. θx was inferior than θy to conventional method. The result suggests that the sign of 0k cannot be determined from extracted outlines.
Optimal scheduling of demand response events using options valuation methods (2011)

Several demand response (DR) programs, such as critical peak pricing (CPP), stipulate that electric utilities may schedule events only a limited number of times per year. Utilities must therefore use these events judiciously in order to maximize their benefits from the DR program. Traditionally, they have used rather simple decision rules to schedule such events (e.g., when temperature exceeds a certain threshold). In this paper, we present an option value approach for determining when to invoke these events. This approach calculates a dynamic threshold value, which represents the option value of deferring the use of one the events for use at any future point in the planning horizon (typically a year or cooling season). This threshold enables utilities to make the decision on whether or not to call an event based on the expected current benefits versus potential future benefits. This paper presents an example based on an actual DR program, which uses a simple, temperature based threshold, and compares it with our option based approach. Our approach can also be applied to any other criteria besides temperature such as reserve margins and generation cost.
The Genetic Legacy of Paleolithic <i>Homo sapiens sapiens</i> in Extant Europeans: A Y Chromosome Perspective (2000)

A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.
Sequence microheterogeneity in the long control region of clinical isolates of human papillomavirus type 16 (1993)

The polymerase chain reaction (PCR) has been used to amplify the long control region (LCR) of episomal human papillomavirus type 16 from cervical scrape DNA obtained from a woman with no evidence of cervical disease and a woman with cervical intraepithelial neoplasia grade 3 (CIN 3). An 883 base pair fragment containing the entire LCR was cloned into pUC13 and the DNA sequence determined for both isolates and compared with the prototype HPV type 16 LCR DNA sequence. Nucleotide variation was apparent in the LCRs derived from both women. In the case of the sample derived from the woman with no cervical disease, there were three nucleotide deletions, one insertion, four transversions, and three transitions (overall conservation: 98.7%). In contrast, the LCR derived from the woman with CIN 3 showed significantly more nucleotide variation with two nucleotide deletions, one insertion, nine transversions, and ten nucleotide transitions (overall conservation 97.6%). Using computer analyses coupled with available data from DNA footprint studies, the effects of these sequence variations on established transcription factor binding sequences were investigated. Cloning of the LCR derived from the woman without cervical disease into a chloramphenicol acetyl transferase (CAT) promoter screening vector, followed by transfection of HeLa cells with the LCR-CAT construct, revealed that the LCR was a functional promoter but was 4.6-fold less active than an equivalent SV40 early promoter-CAT construct.
A Methodology and Implementation for Annotating Digital Images for Context-appropriate Use in an Academic Health Care Environment (2003)

Use of digital medical images has become common over the last several years, coincident with the release of inexpensive, mega-pixel quality digital cameras and the transition to digital radiology operation by hospitals. One problem that clinicians, medical educators, and basic scientists encounter when handling images is the difficulty of using business and graphic arts commercial-off-the-shelf (COTS) software in multicontext authoring and interactive teaching environments. The authors investigated and developed software-supported methodologies to help clinicians, medical educators, and basic scientists become more efficient and effective in their digital imaging environments. The software that the authors developed provides the ability to annotate images based on a multispecialty methodology for annotation and visual knowledge representation. This annotation methodology is designed by consensus, with contributions from the authors and physicians, medical educators, and basic scientists in the Departments of Radiology, Neurobiology and Anatomy, Dermatology, and Ophthalmology at the University of Utah. The annotation methodology functions as a foundation for creating, using, reusing, and extending dynamic annotations in a context-appropriate, interactive digital environment. The annotation methodology supports the authoring process as well as output and presentation mechanisms. The annotation methodology is the foundation for a Windows implementation that allows annotated elements to be represented as structured eXtensible Markup Language and stored separate from the image(s).
Abstract IA12: Combating antigen escape with CD19/CD20 bispecific CAR-T cell therapy (2017)

Abstract T cells expressing chimeric antigen receptors (CARs) specific for the B-cell marker CD19 have shown impressive results in the treatment of B-cell malignancies. However, multiple clinical trials have also demonstrated the vulnerability of single-input CD19 CAR-T cell therapy to antigen escape, in which patients relapse with the emergence of CD19 tumor cells. Here, we report on the rational design and systematic optimization of bispecific CAR-T cells that trigger robust cytotoxicity against target cells expressing either CD19 or CD20. We demonstrate that optimized bi-specific CARs can rapidly eliminate large, engrafted tumors in vivo. We further demonstrate the bi-specific CAR-T cells ability to prevent tumor escape while single-input CD19 CAR-T cells succumb to the selective expansion of CD19 mutant cells, which are shown to arise spontaneously in engrafted mice. The CD19-OR-CD20 CAR is fully compatible with existing T-cell manufacturing procedures and implementable by current clinical protocols. These results present an effective solution to the challenge of antigen escape in CD19 CAR T-cell therapy, and they highlight the utility of structure-based rational design in the development of receptors with higher-level complexity. Citation Format: Eugenia Zah, Meng-Yin Lin, Michael C. Jensen, Anne Silva-Benedict, Yvonne Y. Chen. Combating antigen escape with CD19/CD20 bispecific CAR-T cell therapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA12.