gebhart/patrepeval huggingface dataset:
Abstract 1945: Inhibition of PTK6 kinase activity reduces proliferation and migration of tumor cells (2011)

Abstract Protein kinase 6 (PTK6) is a member of the Frk family of non-receptor tyrosine kinase that is overexpressed in several types of cancers with the highest overexpression observed in breast tumors. PTK6 shows sequence homology to the src tyrosine kinase family. Its functional domains, including a SH3, a SH2 and a kinase domain, are arranged similarly with src family kinases although PTK6 lacks a myristoylation domain. We have identified a potent small molecule PTK6 kinase inhibitor from kinase cross screens that inhibits PTK6 autophosphorylation and phosphorylation of its substrate Sam68, a member of the KH domain containing RNA binding proteins. In cell culture, the compound inhibited proliferation, soft agar growth and migration of tumor cells. The compound inhibited soft agar growth of breast tumor cells more potently than dasatinib. A specific PTK6 kinase inhibitor may provide a novel approach to inhibit the growth of selected tumors, sensitize the response of the tumor cells to other chemotherapeutics and prevent/inhibit metastasis of cancer in a wide range of cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1945. doi:10.1158/1538-7445.AM2011-1945
New Enabling Drug Discovery Technologies – Recent Progress: Virtual Special Issue (2023)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTNew Enabling Drug Discovery Technologies – Recent Progress: Virtual Special IssueStevan W. Djuric*Stevan W. DjuricDiscovery Chemistry and Technology Consulting LLC, New Bern, North Carolina 28562, United States*[email protected]More by Stevan W. DjuricCite this: ACS Med. Chem. Lett. 2023, 14, 10, 1304Publication Date (Web):July 11, 2023Publication History Received16 May 2023Published online11 July 2023Published inissue 12 October 2023https://pubs.acs.org/doi/10.1021/acsmedchemlett.3c00211https://doi.org/10.1021/acsmedchemlett.3c00211editorialACS PublicationsCopyright © 2023 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2410Altmetric-Citations-LEARN 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 PDF (979 KB) Get e-AlertscloseSUBJECTS:Drug discovery,Inhibitors,Medicinal chemistry,Peptides and proteins,Pharmaceuticals Get e-Alerts
Influence of Ion Induced Local Coulomb Field and Polarity on Charge Generation and Efficiency in Poly(3‐Hexylthiophene)‐Based Solid‐State Dye‐Sensitized Solar Cells (2011)

Abstract Dye‐sensitized solar cells (DSSC) are a realistic option for converting light to electrical energy. Hybrid architectures offer a vast materials library for device optimization, including a variety of metal oxides, organic and inorganic sensitizers, molecular, polymeric and electrolytic hole‐transporter materials. In order to further improve the efficiency of solid‐state dye‐sensitized solar cells, recent attention has focused on using light absorbing polymers such as poly(3‐hexylthiophene) (P3HT), to replace the more commonly used “transparent” 2,2′,7,7′‐tetrakis‐( N , N ‐di‐ p ‐methoxyphenyl‐amine)9,9′spiro‐bifluorene (spiro‐OMeTAD), in order to enhance the light absorption within thin films. As is the case with spiro‐OMeTAD based solid‐state DSSC, the P3HT‐based devices improve significantly with the addition of lithium bis(trifluoromethylsulfonyl)imide salts (Li‐TFSI), although the precise role of these additives has not yet been clarified in solid‐state DSCs. Here, we present a thorough study on the effect of Li‐TFSI in P3HT based solid‐state DSSC incorporating an indolene‐based organic sensitizer termed D102. Employing ultrafast transient absorption and cw‐emission spectroscopy together with electronic measurements, we demonstrate a fine tuning of the energetic landscape of the active cell components by the local Coulomb field induced by the ions. This increases the charge transfer nature of the excited state on the dye, significantly accelerating electron injection into the TiO 2 . We demonstrate that this ionic influence on the excited state energy is the primary reason for enhanced charge generation with the addition of ionic additives. The deepening of the relative position of the TiO 2 conduction band, which has previously been thought to be the cause for enhanced charge generation in dye sensitized solar cells with the addition of lithium salts, appears to be of minor importance in this system.
Abstract 12653: The Therapy-related Clonal Hematopoiesis Driver Gene Ppm1d Promotes Inflammation and Non-ischemic Heart Failure in a Murine Model (2020)

Background: Therapy-related clonal hematopoiesis in cancer patients is typically associated with somatic mutations in hematopoietic cell genes that encode regulators of the DNA-damage response (DDR) pathway. The Protein Phosphatase Mg2+/Mn2+ Dependent 1D ( PPM1D ) gene is the most frequently mutated DDR gene associated with therapy-related clonal hematopoiesis. While epidemiological evidence suggests an association between therapy-related clonal hematopoiesis and cardiovascular disease in cancer patients, causal and mechanistic relationships have never been evaluated in an experimental system. Methods: To test whether hematopoietic cell mutations in PPM1D can increase the susceptibility to cardiac stress, we evaluated cardiac dysfunction in response to angiotensin II infusion in a mouse model where clonal-hematopoiesis-associated mutations in Ppm1d were produced by CRISPR-Cas9 technology. Results: Mice transplanted with hematopoietic stem cells containing clinically relevant mutations in exon 6 of Ppm1d exhibited augmented cardiac remodeling following the continuous infusion of angiotensin II. Ppm1d -mutated macrophages showed impairments in the DDR pathway and had an augmented proinflammatory profile. Mice transplanted with Ppm1d mutated cells exhibited elevated IL-1β in the stressed myocardium, and bone marrow derived macrophages produced more IL-1β in response to LPS stimulation. The administration of an NLRP3 inflammasome inhibitor to mice reversed the cardiac phenotype induced by the Ppm1d -mutated hematopoietic stem cells under conditions of Angiotensin II-induced stress. Conclusions: A mouse model of Ppm1d -mediated clonal hematopoiesis was more susceptible to cardiac stress following of angiotensin II infusion. Mechanistically, disruption of the DDR pathway led to elevations in inflammatory cytokine production, and the NLRP3 inflammasome was shown to be essential for this augmented cardiac stress response. These data indicate that therapy-related clonal hematopoiesis involving mutations in PPM1D could contribute to the cardiac dysfunction observed in cancer survivors.
Structural Insights into the Thermus thermophilus ADP-ribose Pyrophosphatase Mechanism via Crystal Structures with the Bound Substrate and Metal (2004)

ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP. This enzyme plays a key role in regulating the intracellular ADP-ribose levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the pyrophosphatase hydrolysis mechanism employed by this enzyme, structural changes occurring on binding of substrate, metal and product were investigated using crystal structures of ADPRase from an extreme thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+) or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose 5'-phosphate and Zn(2+). The structural and functional studies suggested that the ADP-ribose hydrolysis pathway consists of four reaction states: bound with metal (I), metal and substrate (II), metal and substrate in the transition state (III), and products (IV). In reaction state II, Glu-82 and Glu-70 abstract a proton from a water molecule. This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond.
Nuclear Factor Kappa B Over-Activation in the Intervertebral Disc Leads to Macrophage Recruitment and Severe Disc Degeneration (2023)

Overall the observed results suggest prolonged NF-κB activation can induce severe DD, acting through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and inflammatory activation of a macrophage cell populations, that can be mitigated with inflammatory-resolving macrophage secretome.
Light-Scattering Studies of Adsorption of End-Functionalized Polymers in Colloidal Solutions (1993)

We report a light scattering study of the adsorption of end functionalized polymers on colloidal spheres. A scattering method is developed to measure the fraction of polymer molecules adsorbed on the colloidal surfaces. Measurements of the scattering intensity as a function of the polymer-to-colloid molar ratio reveal that only a fraction of the end-functionalized polymers adsorbs on the colloidal surface. The results for the end-functionalized polymers are compared with those for the un-functionalized polymer. It is found that the interaction between the colloid and the un-functionalized polymer is repulsive, which introduces a depletion-attraction between the colloidal particles. The functional end-groups are found to interact attractively with the polar cores of the colloidal particles. The adsorption energy between the functional group and the colloidal surface is estimated to be ~ 4kBT. The presence of the adsorbed polymer on the colloidal surfaces greatly reduces the depletion attraction, and therefore, enhances the stability of the colloid-polymer mixture.
Calcium transport into the cells of the sea urchin larva in relation to spicule formation (2016)

We investigated the manner in which the sea urchin larva takes up calcium from its body cavity into the primary mesenchymal cells (PMCs) that are responsible for spicule formation. We used the membrane-impermeable fluorescent dye calcein and alexa-dextran, with or without a calcium channel inhibitor, and imaged the larvae in vivo with selective-plane illumination microscopy. Both fluorescent molecules are taken up from the body cavity into the PMCs and ectoderm cells, where the two labels are predominantly colocalized in particles, whereas the calcium-binding calcein label is mainly excluded from the endoderm and is concentrated in the spicules. The presence of vesicles and vacuoles inside the PMCs that have openings through the plasma membrane directly to the body cavity was documented using high-resolution cryo-focused ion beam-SEM serial imaging. Some of the vesicles and vacuoles are interconnected to form large networks. We suggest that these vacuolar networks are involved in direct sea water uptake. We conclude that the calcium pathway from the body cavity into cells involves nonspecific endocytosis of sea water with its calcium.
Resolving the CaP-bone interface (2012)

It has long been known that the interfacial relationship between synthetic materials and tissue is influential in the success of implant materials. Instability at the implant interface has been shown, in some cases, to lead to complete implant failure. Bioceramics, and in particular calcium phosphates, form a large fraction of the implantable devices on the market today due to the biocompatibility they exhibit in contact with bone and tooth-like tissues. The characterization of such bioceramic-tissue interfaces has played a crucial role in understanding the behavior of bioceramics in vivo. In this review, we shed light on the preparation methods, technological approaches and key advances in resolving the interface between calcium phosphate bioceramics and bone, and share a future outlook on this field.
Translational value of preclinical models for renal denervation: a histological comparison of human versus porcine renal nerve anatomy (2023)

The distribution of nerve tissue and the relative distribution of extravascular anatomic structures along the renal artery was similar between humans and pigs, which validates the translational value of the normotensive porcine model for RDN.
Interleukin-1 Pretreatment Protects against Endotoxin-Induced Hypotension in Rabbits: Association with Decreased Tumor Necrosis Factor Levels (1993)

Rabbits were infused with either low-dose recombinant human interleukin (IL)-1 beta or vehicle 16 h prior to receiving lipopolysaccharide (LPS). In controls pretreated with vehicle, mean arterial pressure decreased to 68% of the baseline value by 90 min after LPS infusion and remained low for the duration of the study period. In IL-1-pretreated animals, a similar decrease in mean arterial pressure to 69% was observed at 60 min but returned to 90% of baseline after 180 min (P < .05). IL-1-pretreated animals showed no significant rise in serum tumor necrosis factor after LPS infusion compared with vehicle-treated animals (P < .05). Rabbits were pretreated as above with IL-1 and, 40 h later, plasma was transfused into a second group of rabbits just prior to LPS infusion. An infusion of post-IL-1 plasma did not reduce LPS-induced hypotension. Thus, pretreatment with IL-1 reduces the hypotension in response to LPS by a mechanism that is not plasma-mediated but that is associated with reduced serum tumor necrosis factor levels.
Fabrication of Silicon MOSFETs Using Soft Lithography (1998)

Fabrication of metal-oxide semiconductor field-effect transistors (MOSFETs) in silicon using processes in which MIMIC (micromolding in capillaries—a soft lithographic technique) rather than photolithography is used is described. The Figure shows a micrograph of an array of p-MOSFETs obtained from this process. This demonstrates that MIMIC is compatible with Si fabrication processes, and its application is not limited to single-level processes.
CURRENT TREATMENT OF PERIPROSTHETIC FRACTURES (2002)

Periprosthetic fractures are becoming an increasing problem because of the number of total joint replacements that are performed yearly as well as the increase in longevity of the patients that receive total joint replacement. the risk factors for intraoperative fracture are rheumatoid arthritis, cementless arthroplasty, metabolic bone disease, Paget’s Disease, complex deformities, and revisions. The risk factors for post-operative fracture are weakened bone secondary to stress risers, screw holes, cortical perforations and stem tip protrusion, loose implants, and osteolysis. As a general rule the surgeon should make sure that all stress risers such as cortical windows and holes in the diaphysis should be bypassed at least two times the shaft diameter with a longer stem which restores the strength of the shaft to approximately 80%. Areas of transition between stem tips and plates or stem tips and stem tips should be avoided. Cortical strut grafts over holes, windows, and in areas of transition are of value. Johannsen’s Classification with a Type I fracture being proxmial to the tip of the stem, Type II fracture being around the tip of the stem, and Type III fracture distal to the tip of the stem is of value. In a cementless implant the majority of fractures are type I with the minority being Type II and Type III. In periprosthetic fractures with a well fixed prosthesis, the surgeon should maintain the components, restore alignment, and restore function. In periprosthetic fractures with a loose prosthesis, the surgeon should revise the components,restore alignment,and restore function. Treatment options for an intact prosthesis include cerclage wiring in high fractures and the use of plating and allograft struts in lower fractures. With loose implants, treatment options include removal of the implant while maintaining as much bone stock as possible. A loose implant must then be replaced and longer stems and cortical strut grafts are options in the reconstruction. Weight bearing is delayed to allow fracture healing. With this knowledge in hand, the orthopaedic surgeon can anticipate problems and reconstruct bony lesions causing periprosthetic fracture with some confidence in his mechanical constructs.
Effects of shoe bending stiffness and surface stiffness on lower extremity biomechanics during running (2015)

Increasing the forefoot stiffness of footwear has been proposed as a method of reducing athletic injury risk while increasing performance. In terms of injury, footwear with increased forefoot bendi...
Totalsynthese von Altohyrtin A (Spongistatin 1): Teil 2 (1998)

Außerordentlich cytotoxisch sind die aus Meeresschwämmen isolierten Spongipyrane. Sie wirken gegen mehrere menschliche Krebszellinien, wobei das als erste Verbindung dieser Naturstoffklasse isolierte Spongistatin 1 am wirksamsten ist. Die erste Totalsynthese dieses Makrolids wurde nun abgeschlossen. Durch sie wird die von Kitagawa et al. vorgeschlagene relative und absolute Konfiguration bestätigt und nachgewiesen, daß Altohyrtin A und Spongistatin 1 identisch sind.
Continuous separation of biomolecules by the laterally asymmetric diffusion array with out-of-plane sample injection (2002)

The laterally asymmetric diffusion array, a biomolecule sorting device, was used to continuously separate a mixture of T2 and T7 coliphage DNA molecules into its constituents. A two-dimensional array of obstacles (in the presence of an average flow v) can be used to rectify the Brownian motion of particles (in this case DNA molecules) so that they diffuse preferentially in one direction, and perpendicular to the direction of the applied field (in this case an electric field). This type of device had not yet been used for actual fractionation of biomolecules, due to difficulties in injection of the sample. Here we show that with a new injection strategy a well-defined, narrow and continuous stream of molecules can be injected into the separation channel, thus enabling this separation technique to be used in a working device. We expect this type of device could now be employed for separation of a variety of different biomolecules, ranging from long dsDNA to small proteins.
Endocytosis and Intracellular Distribution of PLGA Particles in Endothelial Cells: Effect of Particle Geometry (2009)

Targeting, internalization, and intracellular trafficking of carriers are key processes in drug delivery to endothelial cells. We synthesized PLGA particles with spherical and elliptical disk geometries and investigated the effect of particle shape on rate of particle endocytosis and their intracellular distribution in endothelial cells. Elliptical disks (aspect ratio of 5) were endocytosed at a slower rate compared to spheres (1.8 µm diameter) of the same volume. However, both particles were eventually internalized and accumulated around the nucleus. We quantified the orientation of elliptical disks and found that disks, on average, oriented tangentially with the nuclear membrane. The non-spherical geometry of elliptical disks brings unique aspects to the kinetics and equilibrium distribution of these particles in cells.
A signal-space analysis of spatial self-interference isolation for full-duplex wireless (2014)

The challenge of full-duplex wireless communication is self-interference received directly from the transmit antennas and backscattered from nearby objects. Spatial isolation of the receive antennas from the transmit antennas can mitigate self-interference, but may cause the spatial resources of the channel to be under-utilized, sacrificing spatial multiplexing performance. We present an analysis of spatial isolation of self-interference for full-duplex base stations, which leverages the antenna-theorybased channel model of Poon et. al.We characterize the scattering conditions under which spatial isolation can enable a degrees-of-freedom gain over half-duplex, and show that the gain is inversely proportional to the overlap between the backscattering intervals (set angles of departure/arrival of backscattered self-interference), and the forward scattering intervals (set of angles of departure/arrival to/from the intended users).
787 Natural killer cell engagers activate innate and adaptive immunity and show synergy with proinflammatory cytokines (2021)

<h3>Background</h3> Natural Killer cell Engagers (NKEs) are multifunctional molecules that target activating receptors on the surface of NK cells, bind to tumor associated antigens and engage Fc gamma receptors expressed on effector cells of the immune system. NKEs promote tumor cell lysis by redirecting NK cells to their targets, and drive activation and proliferation of NK cells. Engagement of NK cells, an effector cell population of the innate immune system, provides an opportunity to target cancers with reduced expression of MHC molecules that are less responsive to therapies targeting the adaptive immune system. Therefore, NKEs have a potential to provide an additional treatment option to patients who respond poorly to T cell tailored immunotherapies. <h3>Methods</h3> Expanding on Xencor9s XmAb bispecific Fc platform, we developed NKE molecules targeting NKG2D, an activating receptor expressed on cytotoxic immune cells, B7H3, a pan tumor antigen, while simultaneously engaging Fc gamma receptors. Functional activity of NKEs was evaluated via assessing anti-tumor cytotoxicity and activation of NK and T cells in co-culture studies with human cancer cell lines. <h3>Results</h3> NKEs were engineered for synergistic effects on NK cells by the simultaneous engagement of NKG2D and Fc gamma receptors. Additionally, the NKG2D variable domains were selected for their ability to provide a co-stimulatory signal to T cells in the presence of TCR-mediated signaling. Developed NKEs showed cytotoxic activity and immune cell activation in co-culture studies of human cancer cell lines with either PBMCs, T cells or NK cells. Combination of NKEs with proinflammatory cytokines, such as IL15, showed enhancement of the cytotoxic activity against tumor cells and augmented NK cell activation. <h3>Conclusions</h3> XmAb bispecific NKEs engineered to engage innate and adaptive immunity show encouraging tumor cell killing activity and synergistic cytotoxicity in combination with proinflammatory cytokines. These data have identified several promising candidate NKEs for future in vivo efficacy studies in mouse tumor models expressing B7H3.