gebhart/patrepeval huggingface dataset:
Accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid C-terminal ‘C-tag’ (2017)

Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example. To that end, we have previously reported the expression of a novel protein vaccine for malaria using the ExpreS<sup>2</sup>Drosophila melanogaster Schneider 2 stable cell line system, however, a very low overall process yield (typically <5% recovery of hexa-histidine-tagged protein) meant the initial purification strategy was not suitable for scale-up and clinical biomanufacture of such a vaccine. Here we describe a newly available affinity purification method that was ideally suited to purification of the same protein which encodes the P. falciparum reticulocyte-binding protein homolog 5 - currently the leading antigen for assessment in next generation vaccines aiming to prevent red blood cell invasion by the blood-stage parasite. This purification system makes use of a C-terminal tag known as 'C-tag', composed of the four amino acids, glutamic acid - proline - glutamic acid - alanine (E-P-E-A), which is selectively purified on a CaptureSelect™ affinity resin coupled to a camelid single chain antibody, called NbSyn2. The C-terminal fusion of this short C-tag to P. falciparum reticulocyte-binding protein homolog 5 achieved >85% recovery and >70% purity in a single step purification directly from clarified, concentrated Schneider 2 cell supernatant under mild conditions. Biochemical and immunological analysis showed that the C-tagged and hexa-histidine-tagged P. falciparum reticulocyte-binding protein homolog 5 proteins are comparable. The C-tag technology has the potential to form the basis of a current good manufacturing practice-compliant platform, which could greatly improve the speed and ease with which novel protein-based products progress to clinical testing.
Bone implant interface, osteolysis and potential therapies. (2004)

390 Although total hip replacement (THR) is amongst the most successful and beneficial medical procedures to date, long-term outcomes continue to suffer from aseptic loosening secondary to periprosthetic osteolysis. Extensive research over the last two decades has elucidated a central mechanism for osteolysis in which wear debris generated from the implant stimulates inflammatory cells to promote osteoclastogenesis and bone resorption 1 . Osteolysis can be found in up to 20% of patients 10 years after primary surgery 2-4 , leading to implant failure and the need for revision arthroplasty, which has a poorer clinical result and a shorter duration of survival, compared to primary TJR 5,6 . As a direct consequence of these failures, many younger people who would otherwise be excellent candidates often postpone surgery. Thus, there is a great demand for a therapeutic solution to this problem, which is long overdue. Based on a wealth of knowledge of the cellular and molecular events that govern wear debris-induced osteolysis, and the arsenal of anti-resorptive agents (FDA approved and unapproved drugs), we proposed that two fundamental advances are required to develop a therapeutic intervention for aseptic loosening. The first was a quantitative small animal surrogate to formally evaluate the value of molecular targets through genetics, and the efficacy of drugs with various regimens 7 . The second is a quantitative clinical outcome measure that can accurately measure osteolysis in a longitudinal study 8 . To achieve our first goal, we adapted the mouse calvaria model originally developed to study the resorptive effects of cytokines 9 , and later modified to study wear debris 10 . The
The Kinetics of Replacement Reactions of Complexes of the Transition Metals with 2,2',2"-Terpyridine (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Kinetics of Replacement Reactions of Complexes of the Transition Metals with 2,2',2"-TerpyridineR. H. Holyer, C. D. Hubbard, S. F. A. Kettle, and R. G. WilkinsCite this: Inorg. Chem. 1966, 5, 4, 622–625Publication Date (Print):April 1, 1966Publication History Published online1 May 2002Published inissue 1 April 1966https://pubs.acs.org/doi/10.1021/ic50038a027https://doi.org/10.1021/ic50038a027research-articleACS PublicationsRequest reuse permissionsArticle Views2184Altmetric-Citations244LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The influence of hardening conditions on the properties of masonry cement mortar prisms made in brick moulds (2014)

One aspect of our investigation into the spacing of movement joints involved the short and long term deformation of mortar embedded in masonry. In this research the influence of hardening conditions on the physical and mechanical properties of masonry cement mortar [M5] were studied.\nMortar prisms made in a mould of clay bricks, to evaluate the influence of water suction, have been investigated under different moisture conditions during hardening. During the test period the weight, deformation and strength of the specimens were determined. The results were also compared with similar tests on masonry cement mortar prisms made in steel moulds.\nIn the experimental research a significant influence of the hardening conditions on the final material characteristics of the cement mortar was found. The values of the strength and strain of mortar hardened in steel moulds do not give correct results for calculating the spacing of movement joints in fired clay brick masonry.
Steven Caney's Ultimate Building Book (2006)

This definitive volume details the ins and outs of construction in all its fascinating forms. Ever wondered how a suspension bridge can cross a gap thousands of feet wide? Or what keeps a massive cathedral dome from collapsing? Find out the answers to these and many more questions in Steven Caney's Building Book - a wonderfully comprehensive exploration of design, construction and invention that will stimulate the curiosity of children and adults alike. Packed with exciting building projects guaranteed to engage anyone from 4 to 104, the Ultimate Building Book gives easy-to-follow instructions for creating amazing models and toys that are almost as much fun to make as they are to play with. Readers are also introduced to a wide variety of household materials and tools that can be used for building, along with fascinating insights into the architectural and design properties of everything from drinking straws to yurts. A mammoth project in its own right, this book has been under construction for more than a decade. The result is hundreds of superbly illustrated page that will enlighten and fascinate armchair architects of all ages for years to come.
Research of CWS' Particle Size Distribution based on Ultrasonic Attenuation Theory (2010)

the key to reduce coal pollution is the development of clean coal technology and the improvement of the backward coal-burning technology. The coal water slurry (CWS) is the first substitute of the oil. The particle size distribution of CWS plays an important role in the quality control of CWS. Now there are three methods that are used to analysis the particle size distribution of CWS, screening method, settlement method, laser method. These methods produce some disadvantages when be used to forecast the distribution of CWS. Thus, this article proposes an ultrasonic method with effective medium theory model which can be accurately reflected in the acoustic attenuation characteristics of coal-water slurry based on structural average. Experimental simulation proved that effective medium model is fully capable of achieving on-line detection of coal-water slurry particle size, for detection of fine-and coarse-sized particle size distribution.
Catalytic role of histidine 147 in Escherichia coli thymidylate synthase (1989)

Nine mutant thymidylate synthases were isolated that only differed in sequence at position 147. The wild-type enzyme (which had a histidine residue at 147) and mutant enzymes were purified to near homogeneity and their kinetic properties were compared. Although the kcat values for the mutant enzymes were 10-10,000-fold lower than for the wild-type enzyme, the Km values for both 2'-deoxyuridylate and 5,10-methylenetetrahydrofolate were nearly identical for all the enzymes indicating that His-147 is not significantly involved in initial substrate binding. By comparing the wild-type (His-147) to the glycine (Gly-147) enzyme, the side chain of His-147 was estimated to lower the activation energy of the catalytic step by 1.6-2.9 kcal mol-1. In contrast to the wild-type enzyme, the activity of the Gly-147 enzyme decreased when the pH was raised above 7.5. The activity loss coincided with the deprotonation of a residue that had a pKa of 9.46 +/- 0.2 and an enthalpy of ionization (delta Hion) of 12.1 +/- 0.9. These values are consistent with the involvement of a lysine or an arginine residue in the catalytic process. An inspection of the rates of ternary complex formation among enzyme, 5-fluoro-2'-deoxyuridylate, and 5,10-methylenetetrahydrofolate for the mutant enzymes indicated that His-147 is not needed for the proton removal from C-5 of 2'-deoxyuridylate but rather participates in an initial catalytic step and alters the pKa value of a catalytically important lysine or arginine residue.
Improved copper detection in hydrofluoric acid by recombination lifetime measurements on dedicated silicon substrates (2002)

Copper (Cu) adsorption from diluted hydrofluoric acid (DHF) onto bare silicon surfaces strongly depends on the substrate doping. On highly phosphorus-doped silicon, the adsorption rate is up to three orders of magnitude larger than on moderately doped silicon. This may open a gap between Cu-induced semiconductor device degradation and the detection of Cu contaminations in DHF by minority carrier lifetime measurements. Using dedicated copper monitor wafers where a highly phosphorus-doped backsurface ensures strong Cu adsorption while a moderately doped frontsurface enables minority carrier lifetime measurements, we are able to improve the limit of detection for Cu in DHF by two orders of magnitude.
Fibronectin mediates chemotactic factor-stimulated neutrophil substrate adhesion. (1985)

Plasma fibronectin has been implicated as an important determinant of neutrophil adhesion to plastic surfaces. Using a monoclonal antifibronectin antibody, we examined the role of fibronectin (Fn) in chemotactic factor-mediated neutrophil attachment to various substrates. The chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP) significantly enhanced neutrophil adherence to multiple substrates including gelatin, gelatin coated with Fc fragments of human IgG or Fn, plastic alone, plastic coated with Fc fragments, or purified plasma Fn. An IgM monoclonal antibody to plasma Fn significantly inhibited FMLP-stimulated neutrophil attachment to gelatin, gelatin-Fc, gelatin-Fn, plastic, plastic-Fc, and plastic-Fn substrates when compared with the parent line myeloma supernatant or an irrelevant IgM monoclonal antibody. No reduction in FMLP-stimulated adherence to the gelatin-plasma or plastic-plasma substrates occurred in the presence of antibody. Anti-Fn antibody reduced FMLP-stimulated adhesion only when present during the entire assay; incubation of cells or substrates alone with antibody, followed by removal of excess antibody before addition of stimulus incubation, failed to alter adherence. These data suggest that neutrophil-derived Fn may play a role in chemotactic factor-induced neutrophil adherence to both collagenous and noncollagenous substrates. Further support for the hypothesis was suggested by the demonstration of release of immunoreactive Fn into incubation media from FMLP-stimulated neutrophils.
Sensing A Paradigm Shift in the Field of Molecular Recognition: From Selective to Differential Receptors (2001)

Molecular recognition has evolved from a science designed to understand biological systems into a much more diverse area of research. While work continues to elucidate "nature's tricks" with respect to intermolecular interactions, much attention has turned to the perspective that molecular recognition, by design, can lead to new technologies. Applications ranging from molecular sensing to information storage and even working molecular machines have been envisioned. This review will highlight a few historical hallmarks of molecular recognition oriented at studying the basic science of intermolecular interactions, but then detail recent advances in molecular recognition aimed towards applications in the field of molecular sensing. Rational design can be used to create synthetic receptors with a good deal of predictability and selectivity, and many signal transduction mechanisms exist for converting these receptors into sensors. This is the first topic discussed. The concept of "differential" or "generalized" sensing is then presented, where one uses an array of sensors that do not necessarily conform to the "lock and key" principle. This approach to sensing is inspired by the mammalian senses of taste and smell, which we briefly describe. To mimic senses of taste and smell, one is naturally led to the use of combinatorial libraries, a direction of research that has seen continued growth over the past few years. We summarize the current state of the art in synthetic combinatorial receptors/sensors, and then predict a future direction that the field of molecular recognition will possibly take. The review is not meant for the specialist, but instead for a general audience. It does not present a highly detailed analysis of each individual topic: synthetic receptors, sensors, olfaction/gustation, and combinatorial receptors/sensors. Instead, this review shows how all these fields complement each other and fit together to create sensing devices. Our conclusion is that specific analyte sensing, differential sensing, and combinatorial chemistry can and will be combined to create sensor arrays, and give the subfield of molecular recognition that uses synthetic systems a bright future in this type of sensing scenario.
EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs (2015)

Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations.
Seroma Prevention Using Mytilus edulis Protein in a Rat Mastectomy Model (2006)

Seroma formation is common following mastectomy and autologous breast reconstruction and is a potential cause of significant morbidity in patients. For this reason, many methods have been investigated to prevent this complication. BD Cell-Tak is a tissue adhesive formulated from the proteins excreted by the marine mussel Mytilus edulis. The purpose of this study was to determine if Cell-Tak is able to prevent seroma formation in a rat mastectomy seroma model. Twenty Sprague-Dawley rats underwent unilateral radical mastectomy, partial axillary lymph node dissection, and disruption of the dermal lymphatics. The animals were randomly assigned to either control (n = 10) or experimental groups (n = 10). The experimental animals received 0.3 ml of the topical adhesive in the wound prior to closure, whereas control animals received no treatment. On postoperative day 7, seroma collections were aspirated and quantified and the tissue flaps were sent for histologic analysis. The control rats had a mean seroma volume of 5.3 +/- 2.6 ml, whereas the rats treated with Cell-Tak tissue adhesive had a mean seroma volume of 1.8 +/- 1.5 ml (p < 0.004). Histologic analysis revealed mild inflammation consistent with postoperative changes in both groups and no evidence of foreign body reaction to the adhesive. BD Cell-Tak tissue adhesive significantly reduces seroma formation in the rat mastectomy model. This tissue adhesive may prove beneficial in patients undergoing mastectomy with or without breast reconstruction.
Lupin Peptides Lower Low-Density Lipoprotein (LDL) Cholesterol through an Up-regulation of the LDL Receptor/Sterol Regulatory Element Binding Protein 2 (SREBP2) Pathway at HepG2 Cell Line (2014)

Previous experiments in suitable animal models and in mild hypercholesterolemic individuals have shown that the consumption of lupin proteins may be useful for controlling total and low-density lipoprotein (LDL) cholesterol levels. With the objective of providing evidence that peptides deriving from the hydrolysis of lupin proteins may be responsible of the observed activities and for investigating the mechanism of action, HepG2 cells were treated with lupin peptides obtained by either pepsin (P) or trypsin (T) hydrolysis, and molecular and functional investigations were performed on the LDL receptor/SREBP2 pathway. For the first time, this paper provides experimental evidence that lupin peptides are able to interfere with the HMGCoAR activity, up-regulating the LDL receptor (136 and 84% vs the control for P and T peptides, respectively, at 1 mg/mL) and SREBP2 proteins (148 and 73% vs the control for P and T peptides, respectively, at 1 mg/mL) via the activation of PI3K/Akt/GSK3β pathways and increasing the LDL uptake at HepG2 cell line (40 and 50% vs the control for P and T peptides, respectively, at 1 mg/mL). These results may be useful in explaining the activities observed in vivo in animals and humans treated with lupin protein.
Dynamic Parallelization and Vectorization of Binary Executables on Hierarchical Platforms (2008)

As performance improvements are being increasingly sought via coarse-grained parallelism, established expectations of continued sequential performance increases are not being met. Current trends in computing point toward platforms seeking performance improvements through various degrees of parallelism, with coarse-grained parallelism features becoming commonplace in even entry-level systems. Yet the broad variety of multiprocessor configurations that will be available that dier in the number of processing elements will make it dicult to statically create a single parallel version of a program that performs well on the whole range of such hardware. As a result, there will soon be a vast number of multiprocessor systems that are significantly under-utilized for lack of software that harnesses their power eectively. This problem is exacerbated by the growing inventory of legacy programs in binary executable form with possibly unreachable source code. We present a system that improves the performance of optimized sequential binaries through dynamic recompilation. Leveraging observations made at runtime, a thin software layer recompiles executing code compiled for a uniprocessor and generates parallelized and/or vectorized code segments that exploit available parallel resources. Among the techniques employed are control speculation, loop distribution across several threads, and automatic parallelization of recursive routines. Our solution is entirely software-based and can be ported to existing hardware platforms that have parallel processing capabilities. Our performance results are obtained on real hardware without using simulation. In preliminary benchmarks on only modestly parallel (2-way) hardware, our system already provides speedups of up to 40% on SpecCPU benchmarks, and near-optimal speedups on more obviously parallelizable benchmarks.
Medicare and Medicaid programs; waiver of disapproval of nurse aide training program in certain cases. Final rule. (2010)

This final rule will permit a waiver of a nurse aide training disapproval as it applies to skilled nursing facilities, in the Medicare program, and nursing facilities, in the Medicaid program, that are assessed a civil money penalty of at least $5,000 for noncompliance that is not related to quality of care. This is a statutory provision enacted by section 932 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) (Pub. L. 108-173, enacted December 8, 2003).
Introduction to Surface Plasmon Resonance (2008)

Since its first observation by Wood in 1902 [1,2], the physical phenomenon of surface plasmon resonance (SPR) has found its way into practical applications in sensitive detectors, capable of detecting sub-monomolecular coverage. What is surface plasmon resonance? Wood observed a pattern of “anomalou...
Observation of Biexciton-Resonant Hyper-Parametric Scattering in SiO<sub>2</sub>/CuCl Layered Structures (2007)

We have prepared SiO2/CuCl layered structures and investigated the structural and optical properties, focusing on the observation of biexciton-resonant hyper-parametric scattering that is a promising process to generate entangled photons. A crystalline CuCl film, which is the active layer, was grown on an Al2O3 substrate by a vacuum deposition method, and then an amorphous SiO2 film as the passivation layer for hygroscopic CuCl was prepared by an rf-magnetron sputtering method. X-ray diffraction patterns and optical spectra of excitons indicate that the growth of the SiO2-passivation layer does not degrade the crystallinity of the underlying CuCl thin film. It has been demonstrated that the biexciton-resonant hyper-parametric scattering is clearly observable in the SiO2/CuCl layered structure.
Quantitative analysis of gaseous diffusion in glassy polymers (1970)

Abstract The current theoretical treatment of diffusion of gases in glassy polymers is based on the “dual sorption” model, but also includes certain other important assumptions, at least some of which cannot be fully justified a priori . They require experimental validation, which, however, is not possible by the procedures used or proposed so far. Methods suitable for this purpose are discussed here.
An Analysis of ‘Romans xiii. 8–10’ (1973)

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