gebhart/patrepeval huggingface dataset:
Triphenylphosphine (2005)

[603-35-0] C18H15P (MW 262.30) InChI = 1S/C18H15P/c1-4-10-16(11-5-1)19(17-12-6-2-7-13-17)18-14-8-3-9-15-18/h1-15H InChIKey = RIOQSEWOXXDEQQ-UHFFFAOYSA-N (deoxygenation of ozonides, peroxides, epoxides, and N-oxides; reduction of azides; reduction of organosulfur compounds; dehalogenations) Physical Data: mp 79–81 °C; bp 377 °C; d (solid) 1.18 g cm−3; nD20 1.59. Solubility: insol in H2O; sol in alcohol, benzene, chloroform; v sol in ether. Form Supplied in: white crystalline solid, widely available; polymer supported, ca. 3 mmol P per gram of resin is also available. Purification crystallize from hexane, methanol, or 95% ethanol; dry at 65 °C/<1 mmHg over CaSO4 or P2O5.1 Handling, Storage, and Precautions: classified as an irritant upon acute exposure and a neurological hazard upon chronic exposure.2 It is incompatible with strong oxidizing agents. Arylphosphines are less reactive toward molecular oxygen than benzyl- or alkylphosphines, but air oxidation of triphenylphosphine nonetheless occurs to an appreciable extent, particularly in solution, to give triphenylphosphine oxide.3 Triphenylphosphine has low fire and explosion hazards, but, when heated to decomposition, it emits highly toxic fumes of phosphine and POx.4 Use in a fume hood.
Channel-Dependent Dynamic Frequency Bandwidth Allocation Method Among Service Channels to Maximize Integrated System Throughput (2018)

The fifth generation (5G) mobile communication system is expected to support various wireless communication services such as massive machine-type communications (mMTC), ultra-reliable low latency communications (URLLC), and enhanced mobile broadband (eMBB). These services will serve different numbers of terminals and have different requirements regarding the spectrum efficiency and fairness among terminals. Furthermore, different operators may have different policies regarding the overall spectrum efficiency and fairness among services. We propose a novel channel-dependent dynamic frequency bandwidth allocation method among service channels to maximize the defined system throughput that integrates the system performance of all services considering the above requirements. The proposed method jointly optimizes the time/frequency-domain scheduling and frequency bandwidth allocation among service channels in terms of maximizing the integrated system throughput. Since the proposed method can enhance the multi-user (multi-terminal) diversity gain by performing channel-aware scheduling across the terminals of all services, the integrated system throughput can be further improved compared to a semi-static frequency bandwidth allocation method among service channels previously reported by our group. Extensive computer simulation results show the effectiveness of the proposed method under various system operation scenarios.
Effects of Concurrent and Terminal Visual Feedback on Ankle Co-Contraction in Older Adults during Standing Balance (2021)

This preliminary investigation studied the effects of concurrent and terminal visual feedback during a standing balance task on ankle co-contraction, which was accomplished via surface electromyography of an agonist-antagonist muscle pair (medial gastrocnemius and tibialis anterior muscles). Two complementary mathematical definitions of co-contraction indices captured changes in ankle muscle recruitment and modulation strategies. Nineteen healthy older adults received both feedback types in a randomized order. Following an analysis of co-contraction index reliability as a function of surface electromyography normalization technique, linear mixed-effects regression analyses revealed participants learned or utilized different ankle co-contraction recruitment (i.e., relative muscle pair activity magnitudes) and modulation (i.e., absolute muscle pair activity magnitudes) strategies depending on feedback type and following the cessation of feedback use. Ankle co-contraction modulation increased when concurrent feedback was used and significantly decreased when concurrent feedback was removed. Ankle co-contraction recruitment and modulation did not significantly change when terminal feedback was used or when it was removed. Neither ankle co-contraction recruitment nor modulation was significantly different when concurrent feedback was used compared to when terminal feedback was used. The changes in ankle co-contraction recruitment and modulation were significantly different when concurrent feedback was removed as compared to when terminal feedback was removed. Finally, this study found a significant interaction between feedback type, removal of feedback, and order of use of feedback type. These results have implications for the design of balance training technologies using visual feedback.
Acetyl-CoA Counteracts the Inhibitory Effect of Antiandrogens on Androgen Receptor Signaling in Prostate Cancer Cells (2022)

The commonly used therapeutic management of PC involves androgen deprivation therapy (ADT) followed by treatment with AR signaling inhibitors (ARSI). However, nearly all patients develop drug-resistant disease, with a median progression-free survival of less than 2 years in chemotherapy-naïve men. Acetyl-coenzyme A (acetyl-CoA) is a central metabolic signaling molecule with key roles in biosynthetic processes and cancer signaling. In signaling, acetyl-CoA serves as the acetyl donor for acetylation, a critical post-translational modification. Acetylation affects the androgen receptor (AR) both directly and indirectly increasing expression of AR dependent genes. Our studies reveal that PC cells respond to the treatment with ARSI by increasing expression of ATP-citrate lyase (ACLY), a major enzyme responsible for cytosolic acetyl-CoA synthesis, and up-regulation of acetyl-CoA intracellular levels. Inhibition of ACLY results in a significant suppression of ligand-dependent and -independent routes of AR activation. Accordingly, the addition of exogenous acetyl-CoA, or its precursor acetate, augments AR transcriptional activity and diminishes the anti-AR activity of ARSI. Taken together, our findings suggest that PC cells respond to antiandrogens by increasing activity of the acetyl-coA pathway in order to reinstate AR signaling.
Backfiltration: Past, Present and Future (2011)

Backfiltration has been recognized to be present in most diffusive-convective therapies. Although initially considered an inconvenience due to its implications in transport of contaminants in dialysate to the blood compartment, the availability of ultrapure dialysate has prompted a fresh look at the phenomenon of backfiltration with the possibility of exploiting it to further enhance the convective clearance of middle and large molecules. This review discusses the historical aspects of backfiltration, its mechanisms and influencing factors, and subsequently the different hemodialysis techniques in relation to increasing or diminishing this phenomenon.
Flowability of Gel-Matrix and Magnetorheological Response for Carrageenan Magnetic Hydrogels (2021)

The relationship between rheological features in the absence of a magnetic field and magnetic response was investigated for κ-carrageenan magnetic hydrogels containing carbonyl iron particles. The concentration of carrageenan was varied from 1.0 to 5.0 wt%, while the concentration of carbonyl iron was kept at 70 wt%. The magnetic response revealed that the change in storage modulus Δ<i>G'</i> decreased inversely proportional to the carrageenan concentration. A characteristic strain γ<sub>1</sub> where <i>G</i>' equals to <i>G</i>″ was seen in a strain range of 10<sup>-3</sup>. It was found that Δ<i>G</i>' was inversely proportional to the characteristic stress at γ<sub>1</sub>. Another characteristic strain γ<sub>2</sub> where the loss tangent significantly increased was also analyzed. Similar to the behavior of γ<sub>1</sub>, Δ<i>G</i>' was inversely proportional to γ<sub>2</sub>. The characteristic stresses at γ<sub>1</sub> and γ<sub>2</sub> were distributed at 80-720 Pa and 40-310 Pa, respectively. It was revealed that a giant magnetorheology higher than 1 MPa can be observed when the characteristic stresses at γ<sub>1</sub> and γ<sub>2</sub> are below approximately 240 Pa and 110 Pa, respectively.
High Average Current Electron Guns for High-Power FELs (2009)

Abstract : High average power FELs require high average current electron injectors capable of generating high quality, short duration electron bunches with a repetition rate equal to the frequency of the rf linac. In this paper, we propose, analyze and simulate an rf-gated, gridded thermionic electron gun for use in high average power FELs. In the proposed configuration, the rf-gated grid is modulated at the fundamental and 3rd harmonic of the linac frequency. The addition of the 3rd harmonic on the grid results in shorter electron bunches. In this configuration, every rf bucket of the linac accelerating field contains an electron bunch. PIC simulations indicate that this approach can provide the necessary charge per bunch, bunch duration, longitudinal and transverse emittance, and repetition rate for high average power FELs operating in the IR regime.
Multiple Weyl points and the sign change of their topological charges in woodpile photonic crystals (2017)

Weyl points in photonic systems have gained much attention for their novel properties, such as topologically protected robustness and gapless surface states. However, many Weyl photonic crystal structures designed previously are probably too complicated for nanofabrication. Here, the authors discover that Weyl points can be found in metallic chiral woodpile photonic crystals, which can be fabricated using current nanotechnology. Weyl points with topological charge not only 1 but also 2 can be found in these photonic crystals. When the constituent materials change from the air-in-metal to metal-in-air configuration, the sign of the topological charge will change, leading to a topological phase transition, and the bands change from topologically trivial to nontrivial. Gapless surface states exist in the latter case and robust transport properties have also been demonstrated numerically. When the metallic component is replaced by dielectric materials, such as silicon, the Weyl points still exist. These woodpile photonic crystals should become promising platforms for exploring Weyl point related physics at optical frequencies.
RGS4 Inhibits Signaling by Group I Metabotropic Glutamate Receptors (1998)

Metabotropic glutamate receptors (mGluRs) couple to heterotrimeric G-proteins and regulate cell excitability and synaptic transmission in the CNS. Considerable effort has been focused on understanding the cellular and biochemical mechanisms that underlie regulation of signaling by G-proteins and their linked receptors, including the mGluRs. Recent findings demonstrate that regulators of G-protein signaling (RGS) proteins act as effector antagonists and GTPase-activating proteins for Galpha subunits to inhibit cellular responses by G-protein-coupled receptors. RGS4 blocks Gq activation of phospholipase Cbeta and is expressed broadly in rat brain. The group I mGluRs (mGluRs 1 and 5) couple to Gq pathways to regulate several effectors in the CNS. We examined the capacity of RGS4 to regulate group I mGluR responses. In Xenopus oocytes, purified RGS4 virtually abolishes the mGluR1a- and mGluR5a-mediated but not the inositol trisphospate-mediated activation of a calcium-dependent chloride current. Additionally, RGS4 markedly attenuates the mGluR5-mediated inhibition of potassium currents in hippocampal CA1 neurons. This inhibition is dose-dependent and occurs at concentrations that are virtually identical to those required for inhibition of phospholipase C activity in NG108-15 membranes and reconstituted systems using purified proteins. These findings demonstrate that RGS4 can modulate mGluR responses in neurons, and they highlight a previously unknown mechanism for regulation of G-protein-coupled receptor signaling in the CNS.
The Generation of Monoclonal Antibodies against Human Peroxisome Proliferator-activated Receptors (PPARs) (2002)

Monoclonal antibodies (Mabs) are valuable reagents for the purification, characterization and immunolocalization of proteins. In this study, we raised Mabs against human peroxisome proliferator-activated receptors (PPARs) using baculovirus particles displaying surface glycoprotein gp64-fusion proteins as the immunizing agent. In this system, to display fusion proteins on the viral surface, the amino terminal sequences of human PPARd and PPARg2 are inserted in-frame between the signal sequence and the mature domain of the gp64 nucleotide sequence.Mabs were raised by immunization with whole virus without a purification of the target antigens. The Mabs generated by this novel method were shown to recognize not only the gp64-PPARs fusion protein, but also mature, expressed proteins by a wide variety of techniques, including immunohistochemistry, immunoblotting, and electrophoretic mobility shift assays (EMSAs). Transfection of the transfer vector containing a nucleotide sequence encoding less than 30 amino acids along with linearized baculovirus DNA allows for the production of a high affinity antibody against the corresponding mature form. This method is of potential utility in that it allows the production of valuable antibodies without the requirement of a protein purification step.
Green light-emitting LaPO4 : Ce3+:Tb3+ koosh nanoballs assembled by p-sulfonato-calix[6]arene coated superparamagnetic Fe3O4 (2010)

Superparamagnetic fluorescent nanocomposites based on doped lanthanide phosphate and magnetite nanoparticles are accessible through a facile one-pot method. The bifunctional nanocomposites adopt a koosh ball structure with both fluorescent and superparamagnetic properties for individual components maintained in the final nanostructure.
IDENTIFICATION OF GENOMIC SIGNATURES FOR THE DESIGN OF ASSAYS FOR THE DETECTION AND MONITORING OF ANTHRAX THREATS (2004)

Sequences that are present in a given species or strain while absent from or different in any other organisms can be used to distinguish the target organism from other related or un-related species. Such DNA signatures are particularly important for the identification of genetic source of drug resistance of a strain or for the detection of organisms that can be used as biological agents in warfare or terrorism. Most approaches used to find DNA signatures are laboratory based, require a great deal of effort and can only distinguish between two organisms at a time. We propose a more efficient and cost-effective bioinformatics approach that allows identification of genomic fingerprints for a target organism. We validated our approach using a custom microarray, using sequences identified as DNA fingerprints of Bacillus anthracis. Hybridization results showed that the sequences found using our algorithm were truly unique to B. anthracis and were able to distinguish B. anthracis from its close relatives B. cereus and B. thuringiensis.
Generation of Cation Radicals from 2-Tributylstannyl-1,3-dithianes and Their Reaction with Olefins (1992)

Abstract Oxidation of 2-tributylstannyl-1,3-dithianes with metallic oxidants generates reactive species such as 1,3-dithian-2-yl radical and/or cation by eliminating the stannyl group. Those intermediates react with olefins to give the intermolecular addition products.
Rings, Polymers, and New Materials Containing Phosphorus and Other Main Group Main Elements or Transition Metals (1993)

Abstract Polymers which contain inorganic elements are attracting considerable attention because they provide access to materials with interesting, unusual and potentially useful properties. In this paper we emphasize some of our recent work aimed at exploiting ring-opening polymerization as a route to new inorganic and organometallic polymers containing the main group element phosphorus. For example, attempts to prepare new polymers which also contain boron are reported. In addition, recent results on the ring-opening polymerization of [1]- metallocenophanes such as cyclic ferrocenylsilanes and cyclic ferrocenylphosphines, which possess strained ring-tilted structures, are described. Finally, some recent research on poly(thionylphosphazenes), a novel class of inorganic polymers with sulphur(VI)-nitrogen-phosphorus backbones, is discussed.
Clonostachys rosea: Production by Submerged Culture and Bioactivity Against Sclerotinia sclerotiorum and Bemisia tabaci (2022)

Among the prospective biocontrol agents, the saprophytic filamentous fungus <i>Clonostachys rosea</i> is an excellent necrotrophic mycoparasite of numerous plant pathogenic fungi. However, its commercial development has been hampered by mass production difficulties during solid-state fermentation. Conversely, the submerged liquid fermentation shortens the cultivation time while increasing yields of fungal propagules. However, this method has been overlooked for <i>C. rosea</i>. In this work, we investigated the impact of liquid pre-culture inoculum on the spore production by the two-stage fermentation process using rice grains in comparison to the traditional solid-state fermentation. In parallel, we studied the submerged cultivation of <i>C. rosea</i> by manipulating carbon-to-nitrogen (C:N) ratio and nitrogen source, with the further optimization of spore production in a benchtop bioreactor. Additional bioassays included assessing the bioactivity of water-dispersible microgranules (that contained a submerged conidia) against the whitefly (<i>Bemisia tabaci</i> biotype B) and <i>Sclerotinia sclerotiorum</i> (causal agent of the white mold). Our results showed a maximum concentration of 1.1 × 10<sup>9</sup> conidia/g-dry-matter after 7 days of cultivation by two-stage fermentation process. The liquid fermentation yielded 1.4 × 10<sup>9</sup> submerged conidia/ml after 7 days using a medium with a 50:1 C:N ratio, and it also induced the production of microsclerotia (MS) up to 1.35 × 10<sup>4</sup>/ml within 6 days with 10:1 C:N ratio; both media were supplemented with dextrose monohydrate and soybean meal. The fermentation batches carried out in a benchtop bioreactor with medium 50:1 C:N ratio and amended with soybean meal rendered a production peak on the fourth day, corresponding to 1.11 × 10<sup>9</sup> conidia/ml and 4.35 × 10<sup>8</sup> colony forming units (CFU)/ml. Following air-drying, the conidia production from air-dried microgranules of <i>C. rosea</i> biomass was estimated at 3.4 × 10<sup>10</sup> conidia/g of formulated product upon re-hydration for 7 days. Both submerged conidia and MS of <i>C. rosea</i> inhibited 100% germination of <i>S. sclerotiorum</i> sclerotia by direct parasitism. The air-dried submerged conidia exhibited a suppressive activity on sclerotia (88% mycoparasitism) and early whitefly nymphs (76.2% mortality) that rendered LC<sub>50</sub> values of 3.2 × 10<sup>4</sup> CFU/g soil and 1.5 × 10<sup>7</sup> CFU/ml, respectively. Therefore, the submerged liquid culture of <i>C. rosea</i> may offer a feasible and cost-effective method for its large-scale production, alleviating critical constraints to their commercial use while providing an additional tool for management of <i>B. tabaci</i> and <i>S. sclerotiorum</i>.
Abstract 2963: CDX-585, a novel bispecific antibody targeting PD-1 and ILT4 (2023)

Abstract Both PD-1 and ILT4 (LILRB2, CD85d) have well established immunosuppressive effects that enable tumors to evade anti-tumor immunity. Tumor expression of PD-L1 and ILT4 has been associated with poor clinical outcomes in several cancer types. Recently, ILT4 activation has been postulated as a resistance mechanism for PD-1/PD-L1 blockade prompting the investigation of dual blockade of these pathways. Siu, L.L. et al. (2022 Clin Cancer Res 28: 57-70) reported encouraging results of the initial clinical study combining the ILT4 antagonist mAb MK-4830 with pembrolizumab. The combination was generally well tolerated and led to several durable responses including in PD-1/PD-L1 refractory patients. We have combined novel PD-1 (mAb E1A9) and ILT4 (mAb 7B1) antagonist antibodies into a tetravalent IgG-scFv format bispecific antibody (bsAb, CDX-585). CDX-585 was engineered to avoid effector functionality by eliminating interaction with Fcγ receptors, and to increase its half-life by enhancing binding to FcRn. As expected, CDX-585 inhibits interaction of PD-1 and ILT4 with their ligands, results in potent inhibition of PD-1 signaling and enhances myeloid cell inflammatory responses to stimulation through toll like receptors (LPS) or CD40 (CD40 agonist mAb). In mixed lymphocyte reactions CDX-585 promoted greater T cell activation than the combination of the parental mAbs. Similarly, CDX-585 demonstrated superior anti-tumor activity over the combination of the parental mAbs in a humanized mouse model of melanoma. CDX-585 has completed GMP manufacturing and IND-enabling activities. Doses of CDX-585 up to 60 mg/kg were well tolerated in cynomolgus macaques and displayed a favorable pharmacokinetic profile. Together these data demonstrate that CDX-585 effectively combines PD-1 and ILT4 blockade into one molecule with favorable biophysical and functional characteristics supporting the initiation of a dose-escalation clinical trial in patients with advanced solid tumors. Citation Format: Lawrence J. Thomas, Laura A. Vitale, Michael Murphy, Collin Xia, Zeyu Peng, Asma Ejas, Montu Patel, James Boyer, April R. Baronas, Thomas O'Neill, Jenifer Widger, Laura Mills-Chen, Andrea Crocker, Mark Ma, Mingjiu Chen, Hugh M. Davis, Russ A. Hammond, Cherie Taglienti, Michael Yellin, Joel Goldstein, Diego Alvarado, Henry C. Marsh, Tibor Keler. CDX-585, a novel bispecific antibody targeting PD-1 and ILT4 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2963.
Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement (2021)

The RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data have hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage and then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target modulates Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to "proofreading" capability. Lastly, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.