gebhart/patrepeval huggingface dataset:
Enhancement of antigen-specific immunity via the TLR4 ligands MPL™ adjuvant and Ribi.529 (2003)

MPL (Corixa) adjuvant is a chemically modified derivative of lipopolysaccharide that displays greatly reduced toxicity while maintaining most of the immunostimulatory activity of lipopolysaccharide. MPL adjuvant has been used extensively in clinical trials as a component in prophylactic and therapeutic vaccines targeting infectious disease, cancer and allergies. With over 33,000 doses administered to date, MPL adjuvant has emerged as a safe and effective vaccine adjuvant. Recently, scientists at Corixa Corporation have developed a library of synthetic lipid A mimetics (aminoalkyl glucosaminide 4-phosphates) with demonstrated immunostimulatory properties. Similar to MPL adjuvant, these synthetic compounds signal through Toll-like receptor 4 to stimulate the innate immune system. One of these compounds, Ribi.529 (RC-529), has emerged as a leading adjuvant with a similar efficacy and safety profile to MPL adjuvant in both preclinical and clinical studies.
Involvement of a Polyproline Helix-like Structure in the Interaction of 7B2 with Prohormone Convertase 2 (1996)

The neuroendocrine protein 7B2 is known to be involved in the biosynthesis and activity of prohormone convertase 2 (PC2). Previous studies have demonstrated that while the carboxyl-terminal portion of 7B2 (residues 155-186) regulates the enzymatic activity of PC2, the amino terminus of the molecule (residues 1-151) is required for maturation of proPC2. In this study we employed four different experimental approaches (co-immunoprecipitation with proPC2, facilitation of pro-PC2 maturation, acquisition of enzymatic activity, and thermal protection assays) to identify structural elements of 7B2 important for bioactivity. Inspection of the sequence of 7B2 indicated potential involvement of a polyproline helix-like (PPII) structure, with similarities to those present within SH3 domain ligands, in the interaction of 7B2 with proPC2. Site-directed point mutagenesis of this proline-rich region confirmed the involvement of this area. Replacement of prolines in positions critical to helix formation (Pro90, Pro91, Pro93, and Pro95) either severely impaired or totally abolished 7B2 bioactivity, as gauged by the four assays described. In addition, constructs longer than residues 1-121 were still functional, whereas those shorter than residues 1-109 were not. Computer-assisted analysis predicts the presence of an alpha-helix structure between residues 107 and 123. We conclude that both the proline-rich region and the alpha-helix contribute to 7B2 activity. Polyproline-containing peptides have been shown to be involved in cytoplasmic protein-protein interactions; our results suggest that the polyproline helix motif may also be used to mediate protein-protein interactions within the secretory pathway.
New insight into the nanostructure of ionic liquids: a small angle X-ray scattering (SAXS) study on liquid tri-alkyl-methyl-ammonium bis(trifluoromethanesulfonyl)amides and their mixtures (2009)

We report a small angle X-ray scattering study on the liquid phase of a series of room temperature ionic liquids and their binary mixtures. The ionic liquids studied belong to the tri-alkyl-methyl-ammonium family with bis(trifluoromethanesulfonyl)amide as the anion and were studied as a function of alkyl chain length. These ionic liquids were found to exhibit marked nanoscale ordering in their isotropic liquid state as judged from the small angle X-ray scattering. The observed structural ordering is of supramolecular order and depends strongly on the length of the cation hydrophobic side chain. Moreover, the data can be analyzed on the basis of a disordered smectic A phase, consisting of strongly interdigitated bilayers that sequester the ionic liquid into polar and hydrophobic regions. These findings were also found to be consistent with density data of these molten salts. Additionally, we demonstrate that this experimentally observed nanostructuring can further be fine-tuned using binary mixtures.
Rapid Ertapenem Susceptibility Testing and Klebsiella pneumoniae Carbapenemase Phenotype Detection in Klebsiella pneumoniae Isolates by Use of Automated Microscopy of Immobilized Live Bacterial Cells (2014)

ABSTRACT We evaluated detection of ertapenem (ETP) resistance and Klebsiella pneumoniae carbapenemase (KPC) in 47 Klebsiella pneumoniae isolates using a novel automated microscopy system. Automated microscopy correctly classified 22/23 isolates as ETP resistant and 24/24 as ETP susceptible and correctly classified 21/21 isolates as KPC positive and 26/26 as KPC negative.
Human-Machine Collaborative Systems for Microsurgical Applications (2005)

Human-machine collaborative systems (HMCSs) are systems that amplify or assist human capabilities during the performance of tasks that require both human judgment and robotic precision. We examine the design and performance of HMCSs in the context of microsurgical procedures such as vitreo-retinal eye surgery. Three specific problems considered are: (1) development of systems tools for describing and implementing HMCSs, (2) segmentation of complex tasks into logical components given sensor traces of human task execution, and (3) measurement and evaluation of HMCS performance. These components can be integrated into a complete workstation with the ability to automatically “parse” traces of user activities into task models, which are loaded into an execution environment to provide the user with assistance using on-line recognition of task states. The major contributions of this work include an XML task graph modeling framework and execution engine, an algorithm for real-time segmentation of user actions using continuous hidden Markov models, and validation techniques for analyzing the performance of HMCSs.
Development and testing of a new magnetic-tracking device for image guidance (2007)

Optical tracking systems pioneered the use of position sensors in surgical navigation. The requirement to maintain a clear line-of-sight between the emitters and detectors, however, renders them unsuitable for tracking flexible invasive instruments. On the other hand, advances in electromagnetic tracking systems permit a key-enabling role in imageguided procedures. First-generation magnetic systems present a significant challenge for tracker designers to improve both performance and acceptance. Troublesome magnetic problems include inaccuracies due to the presence of metallic distorters in the tracking volume and to dynamic motion of the tracked object. A new magnetic tracker (3D Guidance<sup>TM</sup>), recently developed at Ascension Technology, seeks to address these problems. Employing third-generation pulsed-DC magnetic tracking technology and new signal processing techniques, the new tracker overcomes the distorting effects of non-magnetic conductive metals (300-series stainless steel, titanium and aluminum) and composite tables experienced by AC trackers. Ascension has developed a break-through flat transmitter that negates ferrous metal distortion emanating from procedural tables. The tracker development has also significantly advanced the state of the art in sensor miniaturization. The 3D Guidance<sup>TM</sup> features the world's smallest electromagnetic tracking sensors, opening the door to new applications for minimally invasive procedures. Finally, dynamic accuracy has been significantly improved with the implementation of Kalman based algorithms. Test results are reported.
Overview of Screen Content Coding in Recently Developed Video Coding Standards (2020)

In recent years, screen content (SC) video including computer generated text, graphics and animations, have drawn more attention than ever, as many related applications become very popular. To address the need for efficient coding of such contents, a number of coding tools have been specifically developed and achieved great advances in terms of coding efficiency. The inclusion of screen content coding (SCC) features in all the recently developed video coding standards (namely, HEVC SCC, VVC, AVS3, AV1 and EVC) demonstrated the importance of supporting such features. This paper provides an overview and comparative study of screen content coding technologies, with discussions on the performance and complexity aspects for the tools developed in these standards.
Augmenting nerve regeneration with electrical stimulation (2008)

The rate limiting process of axon outgrowth, progressive deterioration of both neuronal growth capacity and SC support, but not irreversible target atrophy, account for observed poor functional recovery after nerve injury. Brief ES accelerates axon outgrowth and target muscle reinnervation in animals and humans, opening the way to future clinical application to promote functional recovery.
Recombinant factor VIIa (2005)

Recombinant activated factor VII (rFVIIa, NovoSeven) has been successfully used to treat bleeding episodes in patients with antibodies against coagulation factors VIII and IX. In recent years, rFVIIa has also been employed for the management of uncontrolled bleeding in a number of congenital and acquired haemostatic abnormalities. Based on a literature search, this review examines the current knowledge on therapy with rFVIIa, from the now well-standardized uses to the newer and less well-characterised clinical applications.
Toward Computer-Based Cleavage Site Prediction of Cysteine Endopeptidases (2003)

Identification of relevant substrates is essential for elucidation of in vivo functions of peptidases. The recent availability of the complete genome sequences of many eukaryotic organisms holds the promise of identifying specific peptidase substrates by systematic proteome analyses in combination with computer-based screening of genome databases. Currently available proteomics and bioinformatics tools are not sufficient for reliable endopeptidase substrate predictions. To address these shortcomings the bioinformatics tool 'PEPS' (Prediction of Endopeptidase Substrates) has been developed and is presented here. PEPS uses individual rule-based endopeptidase cleavage site scoring matrices (CSSM). The efficiency of PEPS in predicting putative caspase 3, cathepsin B and cathepsin L cleavage sites is demonstrated in comparison to established algorithms. Mortalin, a member of the heat shock protein family HSP70, was identified by PEPS as a putative cathepsin L substrate. Comparative proteome analyses of cathepsin L-deficient and wild-type mouse fibroblasts showed that mortalin is enriched in the absence of cathepsin L. These results indicate that CSSM/PEPS can correctly predict relevant peptidase substrates.
Elevation of carotenoids in tomato by genetic manipulation (2001)

Abstract Transgenic tomato lines expressing either the Erwinia uredovora phytoene synthase ( crtB ) or phytoene desaturase ( crtI ) gene have been produced using the polygalacturonase (PG) or CaMV 35S promoter respectively. Over three generations, tomato fruits expressing the additional phytoene synthase showed increased total carotenoids approaching twofold. Ripe tomato fruits expressing crtI showed significant increases in β‐carotene (threefold) but a reduction in the total carotenoid content (twofold). The contents of other biosynthetically related isoprenoids, including tocopherols (vitamin E), vitamin K, ubiquinones and plastoquinones, were not altered by manipulations to the carotenoid pathway. Detailed biochemical analysis indicates that both enzymes are targeted to the correct location and reside in active states. Increases in enzyme activity and the levels of carotenoid end‐products do not correlate. The data suggest that enhancement of carotenoids can be achieved by metabolic engineering of the pathway, but intrinsic regulatory mechanisms such as feedback inhibition and metabolite channelling may limit the potential shown by the increased enzyme activities. © 2001 Society of Chemical Industry
Microfluidic Large-Scale Integration: The Evolution of Design Rules for Biological Automation (2007)

Microfluidic large-scale integration (mLSI) refers to the development of microfluidic chips with thousands of integrated micromechanical valves and control components. This technology is utilized in many areas of biology and chemistry and is a candidate to replace today's conventional automation paradigm, which consists of fluid-handling robots. We review the basic development of mLSI and then discuss design principles of mLSI to assess the capabilities and limitations of the current state of the art and to facilitate the application of mLSI to areas of biology. Many design and practical issues, including economies of scale, parallelization strategies, multiplexing, and multistep biochemical processing, are discussed. Several microfluidic components used as building blocks to create effective, complex, and highly integrated microfluidic networks are also highlighted.
A well-defined mesoporous amine silica surface via a selective treatment of SBA-15 with ammonia (2012)

2D double-quantum (1)H-(1)H NMR unambiguously shows that the "isolated" ≡Si-OH surface silanols of dehydroxylated SBA-15 are converted upon treatment with ammonia into single silylamine surface site ≡Si-NH(2). The "gem" di-silanols (=Si(OH)(2)) remain intact. Treatment using HMDS produces (=Si(OSiMe(3))(2)) but leaves ≡Si-NH(2) untouched. The resulting surface is hydrophobic and stable.
Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation (2002)

Sepsis, a potentially fatal clinical syndrome, is mediated by an early (e.g., tumor necrosis factor and IL-1) and late [e.g., high mobility group B-1 (HMGB1)] proinflammatory cytokine response to infection. Specifically targeting early mediators has not been effective clinically, in part because peak mediator activity often has passed before therapy can be initiated. Late-acting downstream effectors, such as HMGB1, that mediate sepsis lethality may be more relevant therapeutic targets. Ethyl pyruvate (EP) recently was identified as an experimental therapeutic that significantly protects against lethal hemorrhagic shock. Here, we report that EP attenuates lethal systemic inflammation caused by either endotoxemia or sepsis even if treatment begins after the early tumor necrosis factor response. Treatment with EP initiated 24 h after cecal puncture significantly increased survival (vehicle survival = 30% vs. EP survival = 88%, P < 0.005). EP treatment significantly reduced circulating levels of HMGB1 in animals with established endotoxemia or sepsis. In macrophage cultures, EP specifically inhibited activation of p38 mitogen-activated protein kinase and NF-kappaB, two signaling pathways that are critical for cytokine release. This report describes a new strategy to pharmacologically inhibit HMGB1 release with a small molecule that is effective at clinically achievable concentrations. EP now warrants further evaluation as an experimental "rescue" therapeutic for sepsis and other potentially fatal systemic inflammatory disorders.
Antitumor Effect of Immunizations With Fusions of Dendritic and Glioma Cells in a Mouse Brain Tumor Model (2001)

SUMMARY: The authors studied antitumor immunity conferred by fusions of dendritic and glioma cells in a mouse brain tumor model. Previous immunization with fusion cells (FCs) prevented tumor formation on challenge with glioma cells in the flank or in the brain. Efficacy was decreased when studies were performed in mice depleted of CD8+ cells. In a treatment model, FCs were injected subcutaneously after tumor development in the brain. The administration of FCs alone had limited effects on survival of mice bearing brain tumors. Importantly, however, administration of FCs and recombinant interleukin-12 (rIL-12) remarkably prolonged the survival of mice with brain tumors. Cytotoxic T lymphocyte activity against glioma cells from immunized mice was also stimulated by coadministration of FCs and rIL-12 compared with that obtained with FCs or rIL-12 alone. These data support the therapeutic efficacy of combining FC-based vaccine therapy and rIL-12.
Identification of surface residues mediating tissue factor binding and catalytic function of the serine protease factor VIIa (1996)

Factor VIIa (VIIa), the serine protease that initiates the coagulation pathways, is catalytically activated upon binding to its cell surface receptor and cofactor tissue factor (TF). This study provides a comprehensive analysis of the functional surface of VIIa by alanine scanning mutagenesis of 112 residues. Residue side chains were defined which contribute to TF binding and factor X hydrolysis. Energetically important binding contacts at the interface with TF were identified in the first epidermal growth factor domain of VIIa (Gln-64, Ile-69, Phe-71, Arg-79) and in the protease domain (Arg-277, Met-306, Asp-309). The observed energetic defects are in good agreement with the corresponding residues in TF, suggesting that the VIIa light chain plays a prominent role in high affinity binding of cofactor. Mutation of protease domain interface residues indicated that TF allosterically influences the active site of VIIa. Stabilization of a labile zymogen to enzyme transition could explain the activating effect of TF on VIIa catalytic function. Residues important for factor X hydrolysis were found in three regions of the protease domain: (i) specificity determinants in the catalytic cleft and adjacent loops, (ii) an exosite near the TF binding site, and (iii) a large electronegative exosite which is in a position analogous to the basic exosite I of thrombin. TF regions involved in factor X activation are positioned on the same face of the TF-VIIa complex as the two exosites identified on the protease domain surface, providing evidence for an extended interaction of TF-VIIa with macromolecular substrate.
Pure and functionally homogeneous recombinant retinoid X receptor. (1994)

Mouse retinoid X receptor alpha (RXR alpha) lacking the amino-terminal region A/B (RXR alpha delta AB) has been purified to more than 98% purity and functional homogeneity from bacterial and baculovirus-based recombinant expression systems with yields of 2-8 mg/liter of culture. The purified protein is soluble, and fluorescence quenching analysis demonstrated that it binds its cognate ligand 9-cis-retinoic acid (9-cis-RA) stoichiometrically, and with high affinity. Compared with RXR delta AB expressed in COS-1 cells, bacterially and baculovirus-expressed proteins bind approximately 10 and 5 times less efficiently to direct repeat 1 (DR1) DNA elements, respectively, suggesting that animal cell-specific modification of RXR or interaction with other animal cell-specific factors may modulate DNA binding. 9-cis-RA did not stimulate DR1 binding of functional RXR delta AB expressed in Escherichia coli, Sf9 or COS-1 cells. The previously reported ligand effect that can be observed with in vitro made receptor may therefore be a consequence of a conformational stabilization of improperly folded in vitro synthesized protein.
Ultrafast Papanicolaou stain. An alternative preparation for fine needle aspiration cytology. (1995)

The objective of this study was to develop a Papanicolaou stain as fast as Diff-Quik yet with cytomorphology as exquisite as that processed by ThinPrep for the optimal evaluation of fine needle aspirates. Satisfactory results were obtained after three modifications were made: (1) rehydration of air-dried smears with normal saline, (2) use of a 4% formaldehyde/65% ethanol fixative, (3) and use of Richard-Allan Hematoxylin 2 and Cyto-stain. The first modification restored the transparency of the cells and hemolysed red blood cells, the second modification reduced the time needed for proper fixation and staining from minutes to seconds, and the third modification simplified the procedure. This 90-second protocol yields a transparent, polychromatic stain with crisp nuclear and cytoplasmic features. The cytomorphology processed by this protocol is at least equal to, if not better than, the quality of specimens prepared by ThinPrep and superior to those processed by the standard Papanicolaou procedure.
Plataforma Digital de Revistas Científicas Electrónicas Españolas: origen, objetivos y gestión del proyecto (2004)

Entre las iniciativas surgidas en todo el mundo enmarcadas dentro del movimiento llamado aceso libre (Open Access), cuyo objetivo final es posibilitar el acceso de forma gratuita a los contenidos de las revistas científicas electrónicas, se presenta por vez primera en España, la creación de una plataforma electrónica dentro de portal Tecnociencia, donde se recojan, seleccionen y alojen las revistas científicas electrónicas españolas y latinoamericana existentes o de nueva creación que cumplan unos requisitos de calidad rigurosos. El acceso a las revistas será gratuito sin que ello menoscabe los principios de calidad que deben regir los textos de las publicaciones integradas en el proyecto. Además, la plataforma contará con otros recursos de valor añadido relacionados con edición electrónica y un espacio restringido para todos los editores que deseen participar en esta iniciativa.
The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist (2009)

Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target. Although the enzyme is highly conserved amongst animals, only the yeast enzyme structure is available for rational drug design. The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence. This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex. The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site. Differences in the observed inhibitor conformation between the yeast and human structures are caused by differing residues in the binding pocket.