gebhart/patrepeval huggingface dataset:
Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody Fusion Devices (2017)

Interbody fusion cages are routinely implanted during spinal fusion procedures to facilitate arthrodesis of a degenerated or unstable vertebral segment. Current cages are most commonly made from polyether-ether-ketone (PEEK) due to its favorable mechanical properties and imaging characteristics. However, the smooth surface of current PEEK cages may limit implant osseointegration and may inhibit successful fusion. We present the development and clinical application of the first commercially available porous PEEK fusion cage (COHERE<sup>®</sup>, Vertera, Inc., Atlanta, GA) that aims to enhance PEEK osseointegration and spinal fusion outcomes. The porous PEEK structure is extruded directly from the underlying solid and mimics the structural and mechanical properties of trabecular bone to support bone ingrowth and implant fixation. Biomechanical testing of the COHERE<sup>®</sup> device has demonstrated greater expulsion resistance versus smooth PEEK cages with ridges and greater adhesion strength of porous PEEK versus plasma-sprayed titanium coated PEEK surfaces. <i>In vitro</i> experiments have shown favorable cell attachment to porous PEEK and greater proliferation and mineralization of cell cultures grown on porous PEEK versus smooth PEEK and smooth titanium surfaces, suggesting that the porous structure enhances bone formation at the cellular level. At the implant level, preclinical animal studies have found comparable bone ingrowth into porous PEEK as those previously reported for porous titanium, leading to twice the fixation strength of smooth PEEK implants. Finally, two clinical case studies are presented demonstrating the effectiveness of the COHERE<sup>®</sup> device in cervical spinal fusion.
M-Best-Diverse labelings for submodular energies and beyond (2015)

We consider the problem of finding M best diverse solutions of energy minimization problems for graphical models. Contrary to the sequential method of Batra et al., which greedily finds one solution after another, we infer all M solutions jointly. It was shown recently that such jointly inferred labelings not only have smaller total energy but also qualitatively outperform the sequentially obtained ones. The only obstacle for using this new technique is the complexity of the corresponding inference problem, since it is considerably slower algorithm than the method of Batra et al. In this work we show that the joint inference of M best diverse solutions can be formulated as a submodular energy minimization if the original MAP-inference problem is submodular, hence fast inference techniques can be used. In addition to the theoretical results we provide practical algorithms that outperform the current state-of-the-art and can be used in both submodular and non-submodular case.
Formation of cyclopentadienyl complexes from tungstenacyclobutadiene complexes and the x-ray crystal structure of an .eta.3-cyclopropenyl complex, W[C(CMe3)C(Me)C(Me)](Me2NCH2CH2NMe2)Cl3 (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFormation of cyclopentadienyl complexes from tungstenacyclobutadiene complexes and the x-ray crystal structure of an .eta.3-cyclopropenyl complex, W[C(CMe3)C(Me)C(Me)](Me2NCH2CH2NMe2)Cl3Richard R. Schrock, Steven F. Pedersen, Melvyn Rowen Churchill, and Joseph W. ZillerCite this: Organometallics 1984, 3, 10, 1574–1583Publication Date (Print):October 1, 1984Publication History Published online1 May 2002Published inissue 1 October 1984https://pubs.acs.org/doi/10.1021/om00088a020https://doi.org/10.1021/om00088a020research-articleACS PublicationsRequest reuse permissionsArticle Views487Altmetric-Citations91LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Semiconductor wafer representation for TCAD (1994)

This work describes the Semiconductor Wafer Representation (SWR) for representing and manipulating wafer state during process and device simulation. The goal of the SWR is to provide an object-oriented interface to a collection of functions designed for developing and integrating Technology CAD (TCAD) applications. By providing functions which can be common across many applications, we aim to greatly reduce tool development and integration time. Corporate, vendor, and university TCAD developers have worked together under the auspices of the CAD Framework Initiative to create an architecture and C++ programming interface for an SWR 1.0 draft standard. Here we describe this architecture and the results of creating and using a prototype implementation of the standard both to integrate existing TCAD tools and to develop simple new tools.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In vitro validation of three-dimensional cavitation-based pressure mapping for quality assessment of clinical high intensity focused ultrasound devices. (2011)

Sufficiently robust and reliable quality assessment (QA) procedures are vital in assuring the widespread adoption of high intensity focused ultrasound (HIFU) for use in both thermal ablation and enhanced drug delivery. Mapping of broadband cavitation emissions in a tissue-mimicking material with a repeatable cavitation threshold offers the potential for rapid, 3-D, cavitation-based pressure mapping of the field produced by a given HIFU transducer. Previous work has demonstrated the viability of this concept, including the design and optimization of a 50-element, cylindrical array capable of mapping a collection of broadband sources distributed throughout a region comparable to the size of a typical HIFU focal volume. The work presented here relates to in vitro experimentation using the array to map cavitating fields produced by a number of HIFU transducers at a range of insonation amplitudes. Results are compared to the predicted size of the cavitation region determined via hydrophone-based characterizations of the HIFU field. Future work will involve using the array to map the instigation and evolution of cavitating fields in three-dimensions in ex vivo tissue during HIFU exposure.
Bulk photoalignment of nematic liquid crystals by addition of azobenzene components (2021)

Surface photoalignment has been utilized to control the liquid crystalline (LC) orientation by exposing the photosensitive surface coatings to linearly polarized light. However, there are limitations in cell thickness and director orientation complexity if surface photoalignment was conducted. An alternative approach in controlling the director orientation is bulk photoalignment. Azobenzenes, which have been used for surface photoalignment due to fast reorientation during exposure, are homogeneously mixed into a nematic LC. We present results on how azobenzene doped LCs can be aligned in various standard orientations. In addition, rewriting alignment and patterning complex director orientations via bulk alignment will be discussed.
Picosecond Pulsed Laser Ablation for the Surface Preparation of Epoxy Composites (2017)

As part of a technical challenge under the Advanced Composites Program, methods for improving pre-bond process control for aerospace composite surface treatments and inspections, in conjunction with Federal Aviation Administration guidelines, are under investigation. The overall goal is to demonstrate high fidelity, rapid and reproducible surface treatment and surface characterization methods to reduce uncertainty associated with the bonding process. The desired outcomes are reliable bonded airframe structure, and reduced timeline to certification. In this work, laser ablation was conducted using a q-switched Nd:YVO4 laser capable of nominal pulse durations of 8 picoseconds (ps). Aerospace structural carbon fiber reinforced composites with an epoxy resin matrix were laser treated, characterized, processed into bonded assemblies and mechanically tested. The characterization of ablated surfaces were conducted using scanning electron microscopy (SEM), water contact angle (WCA) goniometry, micro laser induced breakdown spectroscopy (uLIBS), and electron spin resonance (ESR). The bond performance was assessed using a double cantilever beam (DCB) test with an epoxy adhesive. The surface characteristics and bond performance obtained from picosecond ablated carbon fiber reinforced plastics (CFRPs) are presented herein.
Theoretical and experimental investigation of architected core materials incorporating negative stiffness elements (2014)

Structural assemblies incorporating negative stiffness elements have been shown to provide both tunable damping properties and simultaneous high stiffness and damping over prescribed displacement regions. In this paper we explore the design space for negative stiffness based assemblies using analytical modeling combined with finite element analysis. A simplified spring model demonstrates the effects of element stiffness, geometry, and preloads on the damping and stiffness performance. Simplified analytical models were validated for realistic structural implementations through finite element analysis. A series of complementary experiments was conducted to compare with modeling and determine the effects of each element on the system response. The measured damping performance follows the theoretical predictions obtained by analytical modeling. We applied these concepts to a novel sandwich core structure that exhibited combined stiffness and damping properties 8 times greater than existing foam core technologies.
Discovery of High-Affinity Small-Molecule Binders of the Epigenetic Reader YEATS4 (2022)

A series of small-molecule YEATS4 binders have been discovered as part of an ongoing research effort to generate high-quality probe molecules for emerging and/or challenging epigenetic targets. Analogues such as <b>4d</b> and <b>4e</b> demonstrate excellent potency and selectivity for YEATS4 binding versus YEATS1,2,3 and exhibit good physical properties and in vitro safety profiles. A new X-ray crystal structure confirms direct binding of this chemical series to YEATS4 at the lysine acetylation recognition site of the YEATS domain. Multiple analogues engage YEATS4 with nanomolar potency in a whole-cell nanoluciferase bioluminescent resonance energy transfer assay. Rodent pharmacokinetic studies demonstrate the competency of several analogues as in vivo-capable binders.
Dynamic jamming of dense suspensions under tilted impact (2019)

High-speed ultrasound imaging is used to reconstruct the three-dimensional flow field of dense cornstarch suspensions under tilted impact. Experiments show how jamming fronts propagate and get deformed in a nonaxisymmetric manner under different impact angles.
10.1016/j.ohc.2006.05.005 (2000)

VEGF-A is a critical regulator of ocular angiogenesis and vascular permeability and is involved in the pathogenesis of several ocular diseases involving neovascularization or increased vascular permeability, such as neovascular AMD, diabetic ME, and diabetic retinopathy. Currently available therapies for neovascular AMD, such as laser photocoagulation, PDT with verteporfin, and pegaptanib sodium, slow visual loss but do not improve vision for most patients. In contrast, an emerging anti-VEGF agent, ranibizumab, improved vision in 25% to 34% of treated patients in one clinical trial, rather than slowing visual loss and is the first treatment for neovascular AMD to demonstrate visual improvement in a substantial number of patients. This represents a major advance in the treatment of ocular diseases involving neovascularization or increased vascular permeability and provides hope to patients with these debilitating diseases. Since the submission of this article, ranibizumab was approved by the FDA for the treatment of neovascular AMD.
Privacy-Protecting Algorithms for Digraph Shortest Path Queries (2019)

Trust relation in this work refers to permission that is given to a user at a source-host to access another user at a target-host through an authentication key with a unique fingerprint. The database owner can form a directed graph out of these trust relations, such that user-host pairs are considered nodes and fingerprints as arrows. The authors of this article present a novel protocol to query the shortest path from node A to node B, in a privacy preserving manner. The authors would like to use a cloud to perform such queries, but they do not allow the cloud to learn any information about the graph, nor the query. Also, the database owner is prevented from learning any information about the query, except that it happened.
INGAP-Peptide Variants as a Novel Therapy for Type 1 Diabetes: Effect on Human Islet Insulin Secretion and Gene Expression (2022)

Islet transplantation offers a long-term cure for Type 1 Diabetes (T1D), freeing patients from daily insulin injections. Therapeutic peptides have shown potential to increase the insulin output of pancreatic islets, maximizing the impact of grafted cells. The islet neogenesis-associated protein (INGAP), and its bioactive core (INGAP-P), stimulate beta-cell function and viability, offering the possibility for islet treatment prior to implant. However, dosing efficacy is limited by low circulation time and enzyme degradation. This proof-of-concept study presents the investigation of novel molecular variants of INGAP-P to find a more bioactive form. Custom-designed peptide variants of INGAP-P were synthesized and tested for their effect on the insulin secretion and gene expression of live human islets. We exposed the live islets of five donors to varying glucose concentrations with INGAP-P variants in solution. We identified four peptide variants (I9, I15Tyr, I19 and I15Cys) which displayed statistically significant enhancements over negative controls (representing a 1.6-2.8-fold increase in stimulation index). This is the first study that has assessed these INGAP-P variants in human islets. It highlights the potential for customized peptides for type 1 diabetes therapy and provides a foundation for future peptide-screening experiments.
Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques (2020)

Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.
ChemInform Abstract: FORMATION OF 3‐SUBSTITUTED CYCLOHEXENONES BY NUCLEOPHILIC ADDITION TO ANISOLE‐CHROMIUM COMPLEXES (1980)

Abstract n‐Anisolchromtricarbonyl (I) reagiert mit der Lithium‐Verbindung (II) über ein nicht isoliertes Zwischenaddukt nach Behandlung mit Trif1uoressigsäure und anschließend wäßrigem Ammoniak zum Cyclohexadienol‐ether (III), der zu (IV) verseift wird.
CEP-28122, a Highly Potent and Selective Orally Active Inhibitor of Anaplastic Lymphoma Kinase with Antitumor Activity in Experimental Models of Human Cancers (2011)

Anaplastic lymphoma kinase (ALK) is constitutively activated in a number of human cancer types due to chromosomal translocations, point mutations, and gene amplification and has emerged as an excellent molecular target for cancer therapy. Here we report the identification and preclinical characterization of CEP-28122, a highly potent and selective orally active ALK inhibitor. CEP-28122 is a potent inhibitor of recombinant ALK activity and cellular ALK tyrosine phosphorylation. It induced concentration-dependent growth inhibition/cytotoxicity of ALK-positive anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cells, and displayed dose-dependent inhibition of ALK tyrosine phosphorylation in tumor xenografts in mice, with substantial target inhibition (>90%) for more than 12 hours following single oral dosing at 30 mg/kg. Dose-dependent antitumor activity was observed in ALK-positive ALCL, NSCLC, and neuroblastoma tumor xenografts in mice administered CEP-28122 orally, with complete/near complete tumor regressions observed following treatment at doses of 30 mg/kg twice daily or higher. Treatment of mice bearing Sup-M2 tumor xenografts for 4 weeks and primary human ALCL tumor grafts for 2 weeks at 55 or 100 mg/kg twice daily led to sustained tumor regression in all mice, with no tumor reemergence for more than 60 days postcessation of treatment. Conversely, CEP-28122 displayed marginal antitumor activity against ALK-negative human tumor xenografts under the same dosing regimens. Administration of CEP-28122 was well tolerated in mice and rats. In summary, CEP-28122 is a highly potent and selective orally active ALK inhibitor with a favorable pharmaceutical and pharmacokinetic profile and robust and selective pharmacologic efficacy against ALK-positive human cancer cells and tumor xenograft models in mice.
984 MEK1 within extracellular vesicles inhibits tumor growth by promoting anti-tumor immunity (2022)

<h3>Background</h3> All cells have the capability to produce and release extracellular vesicles (ECVs), small vesicles that have similar topology to the cell and can deliver diverse cargo to mediate cell-cell communication. ECVs derive from the late endosomal pathway and contain bioactive cargo that can include lipids, nucleic acids (both RNA and DNA), and proteins. Once released into the extracellular space, ECVs can bind to and enter other cells, resulting in the physical transfer of bioactive cargo between cells, leading to functional changes in the target cell. Cancer cells secrete more ECVs than non-transformed cells. Tumor-derived (TD) ECVs can affect numerous cell types, including other cancer cells in an autocrine/paracrine manner and non-cancer host cells exerting both pro- and anti-tumor effects on immunity. <h3>Methods</h3> To identify ECV proteins that could modulate immune responses, we have used a model of regressor and progressor cell lines that undergo immune rejection or progressive growth, respectively. We isolated ECVs from these cultured cell lines and performed proteomic analysis of the ECVs to identify unique proteins in ECVs secreted by regressor versus progressor cell lines. Having identified MEK1 as a unique protein in regressor-derived ECVs, we developed a model system to test the effect of MEK1-containing ECVs on tumor immunity. <h3>Results</h3> We found that the signaling molecule MAP2K1 (MEK1) was enriched in ECVs secreted by regressor versus to progressor cells. ECVs engineered to have levels of MEK1 similar to regressor ECVs could inhibit tumor growth. In labeling experiments, ECVs were found to be taken up by tumor macrophages, delivering MEK1 into the cytoplasm, resulting in upregulation of certain genes such as chemokines. In tumors expressing MEK1 in ECVs, the microenvironment was enriched in cytolytic lymphocytes, resulting in induction of genes in the interferon gamma (IFNg) pathway. Blocking IFNg, MEK1 inhibition, or lack of adaptive immunity prevented the effect of MEK1-containing ECVs. Our results support a mechanism by which MEK1 protein within certain ECVs is delivered to tumor macrophages to promote adaptive immune responses against the tumor via IFNg (figure 1). <h3>Conclusions</h3> We conclude that MEK1 activity within exosomes and macrophages promote tumor immunity. These results suggest that the delivery of MEK1 to tumor-associated macrophages, either by ECVs, nanoparticles, or some other means, could be a useful strategy to treat cancer. On the other hand, the use of systemic MEK1 inhibitors in patients could reduce anti-tumor immunity. Therefore, targeting MEK1 inhibition to tumor cells could spare its putative immune suppressive effects. <h3>Acknowledgements</h3> We acknowledge funding and conceptual support from The Hartwell Foundation. <h3>Ethics Approval</h3> Animal studies were approved by the UCSD IACUC under protocol S06201.
Monoclonal antibodies in the analysis of fibronectin isoforms generated by alternative splicing of mRNA precursors in normal and transformed human cells. (1987)

Recent results showing that a single fibronectin gene can give rise to several different mRNAs by alternative splicing have offered an explanation for fibronectin polymorphism. Here we report on monoclonal antibodies that show specificity for a fibronectin segment (ED) that can be included or omitted from the molecule depending on the pattern of splicing of the mRNA precursors. Using these monoclonals, we have quantitatively analyzed the expression of the ED sequence in human fibronectin from different sources. The results demonstrated that, at the protein level, the ED segment is not expressed in plasma fibronectin and that, in fibronectin from the tissue culture medium of tumor-derived or simian virus-40-transformed human cells, the percentage of fibronectin molecules containing the ED segment is about 10 times higher than in fibronectin from normal human fibroblasts. These results suggest that in malignant cells the mechanisms that regulate the splicing of mRNA precursors are altered.