gebhart/patrepeval huggingface dataset:
Asymmetric Catalytic Synthesis of α-Aryloxy Alcohols: Kinetic Resolution of Terminal Epoxides via Highly Enantioselective Ring-Opening with Phenols (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAsymmetric Catalytic Synthesis of α-Aryloxy Alcohols: Kinetic Resolution of Terminal Epoxides via Highly Enantioselective Ring-Opening with PhenolsJoseph M. Ready and Eric N. JacobsenView Author Information Department of Chemistry and Chemical Biology Harvard University, Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1999, 121, 25, 6086–6087Publication Date (Web):June 10, 1999Publication History Received6 April 1999Published online10 June 1999Published inissue 1 June 1999https://doi.org/10.1021/ja9910917Copyright © 1999 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3671Altmetric-Citations156LEARN 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 InReddit Read OnlinePDF (102 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Ethers,Hydrocarbons,Kinetic resolution,Ring opening reactions Get e-Alerts
Preliminary results from a phase 1/2 study of co-stimulatory bispecific PSMAxCD28 antibody REGN5678 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). (2023)

154 Background: Pts with mCRPC have a poor prognosis with limited treatment options, including minimal response to immunotherapies. REGN5678 is a first-in-class, full-length anti-PSMAxCD28 bispecific costimulatory antibody designed to target prostate cancer cells and enhance T-cell activation. We report preliminary results from the dose escalation part of a first-in-human, open-label, Phase 1/2 study (NCT03972657) examining REGN5678 in combination with cemiplimab, a PD-1 blocking antibody. Methods: Pts with mCRPC had received ≥2 lines of systemic therapy in the metastatic and/or castration-resistant setting, including ≥1 second-generation anti-androgen. Pts received REGN5678 weekly at dose levels [DL] 0.1–300 mg, initially as monotherapy for 3 weeks, followed by combination with cemiplimab (350 mg Q3W) until progression or toxicity. Primary objectives are safety, tolerability, and pharmacokinetics. Preliminary efficacy measurements include decline in prostate-specific antigen (PSA) from the start of combination treatment and radiographic response from baseline. Results: At the data cutoff (DCO; July 27 2022), 35 pts had been treated. Treatment-emergent adverse events (TEAEs) ≥Grade (G)3 occurred in 54% (19/35) of pts. Cytokine release syndrome occurred in 6 pts (all G1) and there were 2 dose-limiting toxicities (both G3): pain (at 1 mg) and Guillain-Barré syndrome (at 300 mg). 4 pts (11%) experienced a ≥G3 immune-mediated adverse event (imAE; at DLs 30–300 mg). REGN5678 exposure was non-linear over the tested DLs (more than dose proportional). There were minimal signs of efficacy at lower DLs (REGN5678 0.1–10 mg), with only 1/16 pts showing a PSA decline (of 21%). More PSA declines occurred at higher DLs: 1/4 pts at 30 mg (a PSA decline of 100%), 3/8 at 100 mg (&gt;99%, 44%, 22%), and 3/4 at 300 mg (&gt;99%, 99%, 82%). Notably, all ≥G3 imAEs occurred in pts with PSA declines. Among pts with measurable disease and ≥1 on-treatment scan, radiographic response per RECIST 1.1 occurred in 1/3 pts at 30 mg (complete response), 1/4 at 100 mg (unconfirmed partial response [PR]), and 1/1 at 300 mg (PR confirmed after DCO). Conclusions: Preliminary data on REGN5678 plus cemiplimab in pts with mCRPC provide first evidence of clinical activity of a CD28 co-stimulatory bispecific antibody in solid tumors. Clinical activity was observed at DLs 30–300 mg. ≥G3 imAEs occurred in pts with PSA declines, suggesting a possible association. The study is ongoing to determine the maximum tolerated and recommended Phase 2 doses. Clinical trial information: NCT03972657 . [Table: see text]
Direct synthesis of hydrogen peroxide using Au–Pd-exchanged and supported heteropolyacid catalysts at ambient temperature using water as solvent (2011)

The direct synthesis of hydrogen peroxide from molecular H2 and O2 represents a green and economic alternative to the current anthraquinone process used for the industrial production of H2O2. In order for the direct process to compete with the anthraquinone process, there is a need for enhanced H2O2 yields and H2 selectivity in the process. We show that Au–Pd-exchanged and supported Cs-containing heteropolyacid catalysts with the Keggin structure are considerably more effective in achieving high H2O2 yields in the absence of acid or halide additives than previously reported catalysts. The Au–Pd-exchanged Cs-heteropolyacid catalysts also show superior H2O2 synthesis activity under challenging conditions (ambient temperature, water-only solvent and CO2-free reaction gas). Au plays a crucial role in achieving the improved performance of these heteropolyacid-based catalysts. The heteropolyacid limits the subsequential hydrogenation/decomposition of H2O2.
RFC 4944: Per-Hop Fragmentation and Reassembly Issues (2018)

The first Internet Engineering Task Force (IETF) Working Group (WG) on Internet of Things (IoT), IPv6 over Low power WPAN (6LoWPAN), was established in 2005 to enable mechanisms to transmit Internet Protocol version 6 (IPv6) packets over IEEE 802.15.4. Since IPv6 supports packet sizes larger than the IEEE 802.15.4 maximum frame size, 6LoWPAN WG defined an adaptation layer by standardizing several documents such RFC 4944, RFC 6282 and RFC 6775. RFC 4944 describes the frame format for transmission of IPv6 packets and it defines mechanisms for header compression and fragmentation. RFC 6282 updates RFC 4944, however, it does not reconsider the 6LoWPAN fragment forwarding method. Indeed, considering that IEEE 802.15.4 comes with a Maximum Transmission Unit (MTU) size of 127 bytes, while a IPv6 datagrams with a 1280 byte MTU, an IPv6 packet could be fragmented into more than ten fragments at the 6LoWPAN adaptation layer. Then, using the 6LoWPAN route-over mesh network, the fragmented 6LoWPAN packet must be reassembled at every hop, which eventually causes latency, congestion, interference and packet losses. In this paper, we first provide a thorough background on RFC 4944. We then detail the potential fragment forwarding issues when employing the route over scheme. Finally, we present the ongoing efforts at the IETF to address the undesired issues.
Theoretical and Empirical Investigation into Polymer Blend Morphology in Fiber Spinning (1996)

A promising way of developing new fiber forming materials is by utilization of polymer blends. The morphology of polymer blends has a significant effect on the properties of the resultant fiber. Morphological studies have shown that immiscible additives remain dispersed in the matrix as suspended droplets and that the droplets are elongated into fibrils under the action of shear or extensional forces during processing. The deformability of the dispersed phase is a controlling factor in deciding the resultant morphology and thereby the fiber properties. We report the results of a study of droplet deformation in uniaxial elongational flow under non isothermal conditions. A mathematical model is developed that simulates deformation conditions in fiber spinning. To test our model, a blend of polypropylene and polystyrene was spun into fibers. The blend morphology of the fibers is accurately predicted by the proposed model.
All-Solid-State Garnet Type Sulfurized Polyacrylonitrile/Lithium-Metal Battery Enabled by an Inorganic Lithium Conductive Salt and a Bilayer Electrolyte Architecture (2023)

An all-solid-state garnet Li-S cell with a solid-state sulfur cathode is fabricated by mixing sulfurized polyacrylonitrile (SPAN) with molten lithium bis(fluorosulfonyl)imide (LiFSI) and nano graphene wire (NGW) to improve interfacial contact and ionic and electronic conduction throughout the solid cathode structure. This solid SPAN/LiFSI/NGW cathode was deposited on a dense/porous bilayer garnet structure impregnated on the porous anode side with Li metal and obtained an average discharge capacity of 1400 mAh/g at a current density of 0.167 mA/cm2 (0.1C) for over 40 cycles and of 437 mAh/g at 0.84 mA/cm2 (0.5C) for over 200 cycles for our Li-S cell at 60 °C. This new cathode architecture is a significant advancement toward the development of high-performance all-solid-state Li-S batteries.
Augmenting Digital Sheet Music through Visual Analytics (2022)

Abstract Music analysis tasks, such as structure identification and modulation detection, are tedious when performed manually due to the complexity of the common music notation (CMN). Fully automated analysis instead misses human intuition about relevance. Existing approaches use abstract data‐driven visualizations to assist music analysis but lack a suitable connection to the CMN. Therefore, music analysts often prefer to remain in their familiar context. Our approach enhances the traditional analysis workflow by complementing CMN with interactive visualization entities as minimally intrusive augmentations. Gradual step‐wise transitions empower analysts to retrace and comprehend the relationship between the CMN and abstract data representations. We leverage glyph‐based visualizations for harmony, rhythm and melody to demonstrate our technique's applicability. Design‐driven visual query filters enable analysts to investigate statistical and semantic patterns on various abstraction levels. We conducted pair analytics sessions with 16 participants of different proficiency levels to gather qualitative feedback about the intuitiveness, traceability and understandability of our approach. The results show that MusicVis supports music analysts in getting new insights about feature characteristics while increasing their engagement and willingness to explore.
Broad bandwidth double-trench waveguides in silicon-on-insulator photonic crystal slabs (2004)

We investigate both experimentally and theoretically the waveguiding properties of the novel design of channel waveguides in silicon-on-insulator (SOI) photonic crystal slabs. It is known that the channel waveguides defined by a missing of one row of holes in a triangular-lattice photonic crystal are characterized by a very narrow transmission bandwidth limited by large group velocity dispersion. In order to increase the bandwidth we investigate an alternative design, where the conventional single-mode strip waveguide is embedded into a photonic crystal slab -- a so-called double-trench waveguide. Such a design is intended to combine the best features of photonic crystal slabs, such as suppression of radiation losses at bends and imperfections, with broad bandwidth and small group velocity dispersion. We report the successful demonstration of this broad-bandwidth photonic crystal waveguide with propagation losses as low as 35 dB/cm, which are among the lowest reported in the literature. Furthermore, we found that the modes of positive (quasi-TE) and negative (quasi-TM) parity significantly interact in our structures due to the absence of the oxide layer on top of the SOI slab and the resulting asymmetry. As a result of this interaction multiple mini-stopbands appear in the areas of anti-crossing of the positive and negative parity modes. The results are successfully modeled by the plane-wave calculations confirming the nature of the experimentally observed mini-stopbands. To the best of our knowledge this is the first demonstration of the effects of asymmetry on the transmission characteristics of the photonic crystal slabs.
Audio Information Retrieval (Air) Tools. (2000)

[TODO] Add abstract here.
Abstract 2618: Tumor multicomponent targeting nanoparticle for synergistic killing of drug resistant renal cell carcinoma (2020)

Abstract Targeted therapy in renal cell carcinoma (RCC) has limited clinical response due to the development of drug resistance. Drug resistance can be acquired through multiple pathways including, impairment of apoptosis, overexpression of hypoxia promoting carbonic anhydrase 9 (CA9), and infiltration of folate receptor (FR) positive tumorigenic macrophages. Our hypothesis was to overcome the drug resistance by developing a tumor stimuli-responsive nanoparticle (NP) that can carry combination drugs, such as Cabozantinib (CB) and CFM 4.16 in RCC. The rationale of choosing the CB in combination with CFM4.16 was to induce synergistic anti-RCC effect by modulating the multiple tumor survival pathways, such as caspase 3, Akt/p-Akt, MET. One of the major challenges of the CB and CFM4.16 combination therapy is their poor water solubility and limited targetability to cancer. Thus, we came up with a smart strategy of developing dual folate receptor (FR) and carbonic anhydrase-9 (CA9) biomarker directed nanoparticles that can target the tumor stroma and hypoxia of RCC, respectively. In this proof of concept study, we synthesized SMA-TPGS and SMA polymer (PL) comprising of FR and CA9 dual targeting ligand, namely, FR-CA9-OL using reagent free ‘click' chemistry. FR-CA9-PL was encapsulated either with CFM4.16 or with CB to obtain nanoparticles, called FR-CA9-C4.16 and FR-CA9-CB respectively. The nanoparticles were prepared by using a co-solvent dialysis method that resulted in small-particle size with a range of 80-100 nm diameter, narrow polydispersity index of ∼ 0.15 and high drug loading of 30% (wt./wt.). The homogenous and high drug loading characteristics of nanoparticles are optimal for penetrating hypoxia of RCC. The IC50 of FR-CA9-C4.16 was improved by 60-fold as compared to CFM4.16 treatment and IC50 of FR-CA9-CB is improved by 16-fold compared to CB treatment in aggressive Everolimus-resistant (Evr-res) A498 RCC cells. The combination of FR-CA9-C4.16 with FR-CA9-CB demonstrated synergistic killing of Evr-res-A498 with CI value 0.1-0.5. The signature characteristic and superior anticancer effect of nanoparticles in Evr-resistant RCC provide a worthwhile strategy for overcoming drug resistance in RCC. Citation Format: Kushal Vanamala, Samaresh Sau, Shivani Naik, Arun K. Rishi, Arun Iyer. Tumor multicomponent targeting nanoparticle for synergistic killing of drug resistant renal cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2618.
Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer (2012)

Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF Ab. Of the 2 TF-positive lines, only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, < 5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor-bearing and control mice in an inferior vena cava stenosis model. The results of the present study using a xenograft mouse model suggest that tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis.
3.6.2 Next Generation Requirements Engineering (2012)

Abstract Establishing and managing a “good” set of requirements is one of the critical success factors for any space system project, and for the development of any complex product in general. The NextGenRE project sponsored by the European Space Agency has developed an innovative approach featuring the use of semantic wiki technology to enable users to specify structured, semantically‐rich requirements associated with canonical system designs in OMG SysML. Reuse of requirements through templates is supported, as well as semantic reasoning to check properties such as consistency and coherence among requirements. The approach is entirely model‐based, allowing tight integration of the requirements engineering and design processes and opening the way to the application of model checking and simulation techniques. The new approach is being validated alongside an existing space project.
Nonlinear Deformation Behavior of Bolted Flanges Under Tensile, Torsional, and Bending Loads (2014)

A bolted flange may be subjected to the axial tensile, torsional, and bending external loads in service. The axial tensile, torsional, and bending resistance of the bolted flange is vital for the system vibration, dynamic strength, and reliability. This paper investigates the nonlinear deformation behavior of bolted flanges under tensile, torsional, and bending loads, using finite element analysis (FEA). Even though the bolted flange materials may still deform elastically, the variation in contact area due to the external loading may still cause nonlinear deformation of the flanges. In this study, finite element simulation is used for investigating the respective nonlinear deformation behavior of a preloaded bolted flange under tensile, torsional, and bending loads, and to determine the corresponding stiffness values for each loading.
HER2 c-Terminal Fragments Are Expressed via Internal Translation of the HER2 mRNA (2022)

The HER2/neu signaling pathway is one of the most frequently mutated in human cancer. Although therapeutics targeting this pathway have good efficacy, cancer cells frequently develop resistance. The HER2 gene encodes the full-length HER2 protein, as well as smaller c-terminal fragments (CTFs), which have been shown to be a cause of resistance. Here, we show that HER2 CTFs, exclusive from the full-length HER2 protein, are generated via internal translation of the full-length HER2 mRNA and identify regions which are required for this mechanism to occur. These regions of the HER2 mRNA may present novel sites for therapeutic intervention via small molecules or antisense oligonucleotides (ASOs).
Garlic: A Way Out of Work (2003)

Two 18-year-old men were seen for second-degree burns to the dorsum of their knees, ankles, and feet. Upon investigation, it was revealed that the burns were self-inflicted and resulted from the application of crushed garlic with the intent of exemption from work. Reviews of the literature reveal that garlic-induced burns have been previously reported; however, only once before as a factitious dermatitis. The sharp demarcation line between normal and abnormal skin should suggest that a burn is not from hot liquids. Health care providers had best be advised of the side effects of natural remedies and be aware of how garlic may be abused to the advantage of an individual.
Injection of muscimol, a GABAa agonist into the anterior thalamic nucleus, suppresses hippocampal neurogenesis in amygdala-kindled rats (2008)

The relationship between neurogenesis and epilepsy remains to be solved so far, although aberrant electric circuit recognized in epilepsy might be involved in neurogenesis. In this study, neurogenesis and the proliferation of astrocytes in the subgranular zone of the hippocampus were explored using unilateral amygdala-kindled rats with or without muscimol, a gamma-aminobutyric acid a (GABAa) agonist injection into the bilateral anterior thalamic nuclei (AN). Muscimol injection significantly ameliorated the behavioral scores of epilepsy without any significant alteration on the electroencephalography recorded at the stimulated basolateral amygdala, thus suggesting that muscimol injection might affect the secondary generalization, but not the initial discharge itself. The number of bromodeoxyuridine (BrdU), BrdU/doublecortin and BrdU/glial fibrillary acidic protein-positive cells in the subgranular zone of kindled animals increased markedly. Muscimol injection significantly suppressed neurogenesis, but not the proliferation of astrocyte, in the subgranular zone of the non-stimulated side, probably through the suppression of secondary generalization via AN. The results might indicate the underlying relationships between neurogenesis and epilepsy, that epileptic propagation in unilateral amygdala-kindled rats might go through AN into the contralateral side with subsequent neurogenesis, although further studies need to clarify the hypothesis.
Ultra-Thin Absorbers Comprised by Cascaded High-Impedance and Frequency Selective Surfaces (2015)

The theoretical basis for an ultra-thin broadband absorber is established which is comprised of a mushroom-type high impedance surface (HIS) and a pixelized frequency selective surface (FSS). The latter is engineered to exhibit a prescribed series RLC circuit response and it is placed at an electrically small distance above the HIS. Through a transmission line analysis, it is demonstrated that the admittances of the two structures cancel each other, resulting in an almost zero input reactance and a resistance that fluctuates around that of free space within the frequency range of interest. The resulting structure has a total thickness that does not exceed 2 mm while a - 10 dB return loss is achieved for normal incidence from 9 - 13 GHz.
A Mathematical Model for Cathodic Delamination of Coated Metal Including a Kinetic pH–Porosity Relationship (2008)

A mathematical model for the delamination of coating from active metal was developed in the presence of multiple electrochemical reactions, homogeneous reactions, and precipitation of corrosion product. The computational results illustrate that the propagation of potential front is controlled by the production of ions along the metal–coating interface, while that of porosity front is limited by the rate constant of bond-breakage reactions. The movement of the two fronts are close when the time constant associated with breaking bonds is small as compared to that of diffusion and migration processes. When the time constants of bond-breakage and coating degradation are large, the velocity difference between the potential and porosity fronts becomes large. The delamination rate and delamination mechanism predicted from the model are in good agreement with experimental interpretations. A systematic sensitivity analysis for the fitting parameters used in the program was conducted and the results show that the computations are most sensitive to the parameters in the porosity–pH relation.