gebhart/patrepeval huggingface dataset:
Abstract 4107: Tumor multifunctional targeting polymeric nanomicelles with polypharmacy payload for effective therapy and imaging of resistant renal cell carcinoma (2018)

Abstract Renal cell carcinoma (RCC) is very difficult to treat as the cells are mostly resistant to many current therapies. Therefore, newer treatments including better ways of drug delivery are urgently needed to fight this malignant disease efficiently. The ongoing work was done by generating and characterizing RCC cells that are resistant to everolimus, a front-line mTOR-targeted therapy, and tested whether a class of CARP-1 functional mimetic (CFM) compounds inhibits parental and everolimus-resistant RCCs in combination with sorafenib. CFMs inhibited RCC cell viability in a dose-dependent manner that was comparable to everolimus treatments as well as the combination with sorafenib. CFM-4.16 inhibited viabilities of everolimus-resistant RCC cells, albeit CFM-4.16 combined with sorafenib was more effective than CFM-4.16 alone. CFM-dependent loss of RCC cell viabilities was due in part to reduced cyclin B1 levels, activation of pro-apoptotic, stress-activated protein kinases (SAPKs), and apoptosis. However, CFMs and sorafenib are hydrophobic, and their dose escalation for in vivo studies remains challenging. We addressed the solubility and delivery concerns of CFM-4.16 and sorafenib by utilizing a nanotechnology-based approach. Our data thus far revealed that we have been successful in overcoming the solubility concerns of CFM-4.16 and sorafenib by encapsulating it in water-soluble vitamin E TPGS-based micellar nanoformulation that enables high drug loading and affords its intravenous administration for animal testing. We also use our polymeric NPs formulation for in vitro efficacy in parental, wild-type and everolimus-resistant RCC. After confirming the anticancer activity of CFM-4.16-loaded nanoformulations in vitro, we finally examined the intravenous (i.v.) administration of the CFM-4.16-loaded polymeric NPs in a clinically relevant RCC mouse model. The CFM-4.16 formulation inhibited the viability of parental and everolimus-resistant RCC cells in vitro and suppressed the growth of parental A498 RCC-cell-derived xenografts (RCC animal model), in part by stimulating apoptosis. After optimizing its potency and biologic stability, we performed imaging of animal inoculated with RCC tumor and PDX model by conjugation with NIR dye. The results showed high binding affinity and specific tumor uptake, faster normal tissue clearance and less non-target organ uptake. These findings make CFM-4.16 an important potential therapeutic in combination with sorafenib using nanoformulation in the treatment of RCCs. Citation Format: Hashem O. Alsaab, Samaresh Sau, Vino T. Cheriyan, Ulka Vaishampayan, Arun K. Rishi, Arun K. Iyer. Tumor multifunctional targeting polymeric nanomicelles with polypharmacy payload for effective therapy and imaging of resistant renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4107.
Synthesis, Stability, Antiviral Activity, and Protease-Bound Structures of Substrate-Mimicking Constrained Macrocyclic Inhibitors of HIV-1 Protease (2000)

Three new peptidomimetics (1-3) have been developed with highly stable and conformationally constrained macrocyclic components that replace tripeptide segments of protease substrates. Each compound inhibits both HIV-1 protease and viral replication (HIV-1, HIV-2) at nanomolar concentrations without cytotoxicity to uninfected cells below 10 microM. Their activities against HIV-1 protease (K(i) 1.7 nM (1), 0.6 nM (2), 0.3 nM (3)) are 1-2 orders of magnitude greater than their antiviral potencies against HIV-1-infected primary peripheral blood mononuclear cells (IC(50) 45 nM (1), 56 nM (2), 95 nM (3)) or HIV-1-infected MT2 cells (IC(50) 90 nM (1), 60 nM (2)), suggesting suboptimal cellular uptake. However their antiviral potencies are similar to those of indinavir and amprenavir under identical conditions. There were significant differences in their capacities to inhibit the replication of HIV-1 and HIV-2 in infected MT2 cells, 1 being ineffective against HIV-2 while 2 was equally effective against both virus types. Evidence is presented that 1 and 2 inhibit cleavage of the HIV-1 structural protein precursor Pr55(gag) to p24 in virions derived from chronically infected cells, consistent with inhibition of the viral protease in cells. Crystal structures refined to 1.75 A (1) and 1.85 A (2) for two of the macrocyclic inhibitors bound to HIV-1 protease establish structural mimicry of the tripeptides that the cycles were designed to imitate. Structural comparisons between protease-bound macrocyclic inhibitors, VX478 (amprenavir), and L-735,524 (indinavir) show that their common acyclic components share the same space in the active site of the enzyme and make identical interactions with enzyme residues. This substrate-mimicking minimalist approach to drug design could have benefits in the context of viral resistance, since mutations which induce inhibitor resistance may also be those which prevent substrate processing.
Digital Coherent Receivers for Long-Reach Optical Access Networks (2012)

The relative merits of coherent-enabled optical access network architectures are explored, with a focus on achievable capacity, reach and split ratio. We review the progress in implementing the particular case of the ultra dense wavelength division multiplexed (UDWDM) passive optical network (PON), and discuss some challenges and solutions encountered. The applicability of digital signal processing (DSP) to coherent receivers in PONs is shown through the design and implementation of parallelized, low-complexity application-specific digital filters. In this work, we focus on mitigating the impact of local oscillator laser (LO) relative intensity noise (RIN) on receiver sensitivity, and propose an algorithm which compensates for this impairment. This phenomenon is investigated theoretically and then experimentally by evaluating the sensitivity of a coherent receiver incorporating different tunable light sources; a low-RIN external cavity laser (ECL) and a monolithically integrated digital supermode distributed Bragg reflector (DS-DBR) laser. It is shown that the RIN of the signal laser does not significantly contribute to the degradation of the receiver sensitivity. Finally, a 10 Gbit/s coherent PON is demonstrated using a DS-DBR laser as the LO laser. It is found that a receiver sensitivity of -38.8 dBm is achievable assuming the use of hard-decision forward error correction.
Class III β-tubulin in human retinal pigment epithelial cells in culture and in epiretinal membranes (1995)

The class III beta-tubulin isotype (beta III) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in 1 day-old primary cultures; however, beta III is present in RPE cells in 5-day primary cultures and in passaged RPE cells grown in monolayer cultures as determined by immunohistochemistry and Western blotting. beta III-positivity in cultured RPE cells is not affected by cell density or hydroxyurea- or retinoic-acid-mediated growth inhibition, but only a few cells weakly express beta III in cyclohexamide-treated cultures and RPE cells maintained in serum-free medium fail to produce beta III. When monolayer-cultured RPE cells grown in normal, serum-containing medium, are transferred to irradiated bovine vitreous, beta III is undetectable in most cells. Cultured RPE cells coexpress beta III with keratin and cellular retinaldehyde-binding protein (both RPE cell markers), but not with glial fibrillary acidic protein. Some cultured RPE cells also express neuron-specific (gamma) enolase, which is neuron-associated but not neuron-specific, and occasional cells in confluent or super-confluent cultures contain the 200-kDa neurofilament protein. Retinal glia, fibroblasts, endothelial cells, and smooth muscle cells do not express beta III under the same culture conditions. We have detected beta III in 45 of 56 epiretinal membranes, frequently in cells with a bipolar or dedifferentiated morphology, where its expression coincides with other RPE cell-associated antigens. Cells with morphological features resembling normal RPE cells in epiretinal membranes are usually negative for beta III, but RPE cells appearing to be in the early stages of dedifferentiation express the isotype weakly. Electron microscopic immunocytochemistry localizes beta III to microtubules, ribosomes and cytoplasm. beta III may be a useful marker for recognizing the fraction of RPE cells in epiretinal membranes that are no longer identifiable by morphological criteria or other RPE cell markers. These findings demonstrate that mature human RPE cells have the capacity to express a neuron-associated gene in response to conditions that promote dedifferentiation.
Improvement of the Reliability of Dielectrics for MLCC (2011)

To achieve enough reliability of monolithic ceramic capacitor, it is important to know the contribution of grain boundary and grain interior to its reliability and insulation resistance. As the number of grain boundaries per layer increased, mean time to failure (MTTF) increased. In addition, as the number of grain boundaries per layer increased, samples showed lower current leakage in the measured electric field range. Using these data, the grain boundary E-J curves were determined by simulation. As a result, temperature and electric field dependence of insulation resistance of grain boundary were very low. The insulation characteristics of one BaTiO3 grain per layer were examined. The resistance and reliability of grain interior were very low. To improve the degradation resistance of grain interior, Ca-doped BaTiO3-based dielectrics were developed. The influence of Ca substitution on MTTF was investigated and it was found out that MTTF increased with the increase of Ca substitution.
Biodegradable Compatibilizers for Poly(hydroxyalkanoate)/Poly(ε-caprolactone) Blends through Click Reactions with End-Functionalized Microbial Poly(hydroxyalkanoate)s (2019)

Poly(hydroxyalkanoate)s (PHAs) have gained significant attention because they readily biodegrade even under environmental conditions; however, expanding the applications of these polymers to a number of fields is hindered by their brittle nature. Blending with a soft biodegradable polymer, such as poly(ε-caprolactone) (PCL), is currently the best solution for improving the toughness of a PHA material without sacrificing biodegradability; consequently, the development of biodegradable compatibilizers is strongly desired. This Article describes a systematic investigation into the compatibilizing abilities of a number of architecturally varied block copolymers (BCPs) composed of microbially derived poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(3HB-co-3HHx); PHBH as the A block) and PCL (as the B block), including AB-, A2B-, AB2-, ABA-, and A2BA2-type BCPs. These BCPs were precisely synthesized through the click reactions of azido-functionalized PCLs with microbially produced propargyl-end-functionalized PHBH. Transmission electron microscopy and tensile-testing experiments reveal that the mechanical properties of PHBH/PCL/BCP (= 67/23/10 wt %) ternary blends are highly dependent on the choice of BCP architecture and are closely related to their morphologies. A remarkable 5–10-fold increase in elongation at break compared to that of the BCP-free blend (PHBH/PCL = 75/25) was achieved by the addition of the ABA- or A2BA2-type BCP as the compatibilizer.
Influence of myopic macular degeneration severity on treatment outcomes with intravitreal aflibercept in the MYRROR study (2019)

Visual acuity gains, morphological outcomes and dosing frequency were not affected by baseline MMD severity in patients treated with IVT-AFL. A benefit with IVT-AFL treatment was observed for all baseline MMD stages included in this study.
Effect of the position of lateral fluoro substituents on the phase behaviour and ferroelectric properties of chiral 1-methylheptyl 4′-[(2- or 3-fluoro-4-tetradecyloxyphenyl)propioloyloxy]biphenyl-4-carboxylates (1994)

The syntheses of four chiral laterally fluoro-substituted propiolate esters are described, along with transition temperatures, ferroelectric properties, phase diagrams and related data. The position of the fluoro-substituent was found to influence dramatically the formation of twist grain boundary (TGB A* and TGB C*) phases as well as the magnitudes of spontaneous polarization and optical tilt angle in the ferroelectric smectic C* mesophases. Differential scanning calorimetric studies revealed the presence of a diffuse liquid-liquid transition above the clearing point in both of the 3-fluoro enantiomers, but not in the racemate. Circular dichroism and optical rotation measurements, carried out over a temperature range in which the diffuse peak occurs, appear to confirm the presence of a degree of chiral organization within the isotropic liquid. It is suggested that this phenomenon may be due to the presence of cybotactic groups or a network of entangled screw dislocations occurring close to the clearing point.
Enantio- and Diastereoselective Total Synthesis of EI-1941−1, −2, and −3, Inhibitors of Interleukin-1β Converting Enzyme, and Biological Properties of Their Derivatives (2005)

[reaction: see text] The first asymmetric total synthesis of EI-1941-1, -2, and -3, inhibitors of the interleukin-1beta converting enzyme (ICE), has been accomplished, starting from a chiral epoxy iodoquinone 11, a key intermediate in our total synthesis of epoxyquinols A and B. Despite a failure to synthesize the inhibitors by our postulated biosynthetic route, we were able to diastereoselectively synthesize them via an intramolecular carboxypalladation with the key steps being a 6-endo cyclization mode followed by beta-hydride elimination. The investigation of the biological properties of EI-1941-1, -2, and -3 and their derivatives disclosed them to be potent and effective ICE inhibitors with less cytotoxicity than EI-1941-1 and -2 in a cultured cell system.
Engineering bone‐like tissue in vitro using human bone marrow stem cells and silk scaffolds (2004)

Porous biodegradable silk scaffolds and human bone marrow derived mesenchymal stem cells (hMSCs) were used to engineer bone-like tissue in vitro. Two different scaffolds with the same microstructure were studied: collagen (to assess the effects of fast degradation) and silk with covalently bound RGD sequences (to assess the effects of enhanced cell attachment and slow degradation). The hMSCs were isolated, expanded in culture, characterized with respect to the expression of surface markers and ability for chondrogenic and osteogenic differentiation, seeded on scaffolds, and cultured for up to 4 weeks. Histological analysis and microcomputer tomography showed the development of up to 1.2-mm-long interconnected and organized bonelike trabeculae with cuboid cells on the silk-RGD scaffolds, features still present but to a lesser extent on silk scaffolds and absent on the collagen scaffolds. The X-ray diffraction pattern of the deposited bone corresponded to hydroxyapatite present in the native bone. Biochemical analysis showed increased mineralization on silk-RGD scaffolds compared with either silk or collagen scaffolds after 4 weeks. Expression of bone sialoprotein, osteopontin, and bone morphogenetic protein 2 was significantly higher for hMSCs cultured in osteogenic than control medium both after 2 and 4 weeks in culture. The results suggest that RGD-silk scaffolds are particularly suitable for autologous bone tissue engineering, presumably because of their stable macroporous structure, tailorable mechanical properties matching those of native bone, and slow degradation.
Decreased Striatal Vesicular Monoamine Transporter Type 2 Correlates With the Nonmotor Symptoms in Parkinson Disease (2019)

The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.
Room-Temperature Micron-Scale Exciton Migration in a Stabilized Emissive Molecular Aggregate (2016)

We report 1.6 ± 1 μm exciton transport in self-assembled supramolecular light-harvesting nanotubes (LHNs) assembled from amphiphillic cyanine dyes. We stabilize LHNs in a sucrose glass matrix, greatly reducing light and oxidative damage and allowing the observation of exciton-exciton annihilation signatures under weak excitation flux. Fitting to a one-dimensional diffusion model, we find an average exciton diffusion constant of 55 ± 20 cm<sup>2</sup>/s, among the highest measured for an organic system. We develop a simple model that uses cryogenic measurements of static and dynamic energetic disorder to estimate a diffusion constant of 32 cm<sup>2</sup>/s, in agreement with experiment. We ascribe large exciton diffusion lengths to low static and dynamic energetic disorder in LHNs. We argue that matrix-stabilized LHNS represent an excellent model system to study coherent excitonic transport.
Simultaneous enzymatic saccharification and comminution for the valorization of lignocellulosic biomass toward natural products (2018)

SESC is very promising for the mild and clean processing of lignocellulose to generate glucose and unmodified lignin in a large scale. Economic feasibility is highly dependent on its potential to generate high value natural products for energy, specialty chemicals, feed and food application.
Giant Davydov splitting of the lower polariton branch in a polycrystalline tetracene microcavity (2008)

We demonstrate strong exciton-photon coupling of Frenkel molecular excitons at room temperature in an all-metal microcavity containing a thin film of crystalline tetracene, with micron scale domains. In contrast to previous reports of strong coupling in organic microcavities containing localized excitonic states, here we observe large Davydov splitting of the lowest excited state, indicating strong, intermolecular interactions. The angle-resolved reflectivity of the microcavity is measured and understood in terms of the anisotropic dielectric constant of tetracene single crystals. The anisotropy leads to the formation of additional normal modes, and a giant splitting of the lower polariton branch is observed due to birefringence along both Davydov components.
Inhibition of EGFR Signaling: All Mutations Are Not Created Equal (2005)

Gazdar and Minna discuss the context and implications of a research article that examines the transformation potential and response to inhibitors of specific EGFR mutations found in lung cancer.
Synthesis and Bioactivity of a Brasilicardin A Analogue Featuring a Simplified Core (2015)

An analogue 2 of Brasilicardin A, 1 (BraA), a potent immunosuppressive and cytotoxic agent, was synthesized in which the natural tricyclic skeleton was replaced with a synthetically more accessible substituted tetrahydronaphthalene core. BraA, this analogue (BraL), and cyclosporine A were tested for their ability to inhibit the proliferation of human T cells upon CD3/CD28 activation. Although BraL did not impact T cell activation over the dose range tested, this study shows the inhibitory activity of BraA on human T cells for the first time.
Expression of Liver-Specific Functions by Rat Hepatocytes Seeded in Treated Poly(Lactic- co -Glycolic) Acid Biodegradable Foams (2001)

Techniques of liver replacement would benefit patients awaiting donor livers and may be a substitute for transplantation in patients whose livers can regenerate. Poly(lactic-co-glycolic acid) (PLGA) copolymers are biodegradable and have been shown to be useful as scaffolds for seeding and culturing various types of cells. In this study, foam disks were prepared from PLGA (lactic-to-glycolic mole ratio of 85:15) by lyophilization of benzene (5% w/v) solutions. These disks were then used as scaffolds for rat hepatocyte culture. Foams were coated with either a type I collagen gel (0.1% w/v), coated with gelatin (5% w/v), or treated with oxygen plasma (25 W, 90 s) to modify their surface chemistry and wettability. The disks were then seeded with rat hepatocytes (10(6)/mL) and cultured for a period of 2 weeks. All surface treatments resulted in increased hydrophilicity, the greatest being obtained by collagen treatment (contact angle < 10 degrees ), and a minimal decrease in void fraction (5%). DNA content after a 2-week culture period increased proportionally with the wettability of the treated foam surface. Urea synthesis in untreated foams averaged 15.3 +/- 2.3 microg/h/microg DNA, which was significantly higher than that for controls, whereas gelatin and collagen treated foams exhibited urea synthetic rates below the control levels at all times. The DNA content decreased significantly by about 50% between days 1 and 12. PLGA foams, treated and untreated, represent a promising scaffold for scaling up hepatocyte cultures.
Associative Microgels, New Self Adaptive Systems to Control Fluid Loss in Well Cementing (2021)

Abstract Fluid loss control additives are critical constituents in a cement slurry formulation to ensure even cement placement and ultimately satisfactory zonal isolation. Many technological options have been developed over the past decades to design fluid loss control additives for cementing. The most popular technologies as of today are either based on water soluble polymers or colloidal particles like latexes. As an alternative approach, in this paper we introduce a new technology based on associative or "sticky" microgels. These microgels are able to associate with one another at elevated concentration but, more surprisingly, are also able to associate under shear in the dilute regime during a filtration process. As a consequence these additives demonstrate outstanding performance as fluid loss control agents. This study focuses first on standard API filtration tests using sticky microgels, and on how their behavior in application differs from traditional systems, in particular water-based soluble polymers such as cellulosic derivatives or synthetic polymers. Our investigations then focus on the working mechanism of the microgel system by analyzing adsorption on the cement surface, rheology, and filter cake structure using Mercury Intrusion Porosimetry (MIP). Finally the behavior of sticky microgels in model filtration tests is explored with either filtration against porous ceramic discs or using microfluidic chips allowing a direct visualization of microgels during filtration. This study demonstrates that associative microgels are not controlling fluid loss through a simple size match between particles and pores within the filter cake but rather through shear-induced aggregation. Microfluidic observations reveal that aggregation occurs irreversibly as microgels are forced through the pores as the filtration process occurs. The shear-induced associated gels are particularly effective at reducing dramatically the filter cake permeability and allowing gas migration control. Interestingly the shear-induced aggregation of associative μgels seems to confer self-adaptive properties of the fluid loss additives with respect to the pore network to be clogged. Indeed, formation of shear aggregated gels larger than the individual microgels can be used to limit fluid loss even if the pore sizes are much larger than the individual microgels.
Table S3 from Intratumoral Plasmid IL12 Expands CD8<sup>+</sup> T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti–PD-1 Therapy (2023)

&lt;p&gt;Table S3&lt;/p&gt;