gebhart/patrepeval huggingface dataset:
Abstract 2392: CDX-527: A novel bispecific immune-modulating antibody targeting CD27 and PD-L1 (2019)

CD27 is a costimulatory molecule that provides a complementary target to the PD-1/PD-L1 axis on T cells. Combining a CD27 agonist monoclonal antibody (mAb) with PD-1/PD-L1 blockade has been shown to promote synergistic antitumor activity in preclinical models. In advanced cancer patients, the combination of the CD27 agonist mAb, varlilumab, with the PD-1 mAb, nivolumab, was generally well tolerated, induced strong biological effects, and led to sustained clinical responses in some patients that generally have low response rates to checkpoint inhibitors. We theorized that combining CD27 costimulation with PD-1/PD-L1 blockade in a bispecific antibody (bsAb) may provide greater immune activating properties than combining the individual mAbs due to enhanced CD27 activation by crosslinking through PD-L1 in addition to Fc receptors. To test this approach, we developed CDX-527, a tetravalent human anti-CD27/PD-L1 IgG1 bsAb. CDX-527 inhibits PD-1 signaling in vitro in a manner similar to clinically approved PD-1/PD-L1 antibodies. CDX-527 also elicits potent T cell costimulation through PD-L1 crosslinking as measured by cytokine induction and cell proliferation, whereas the PD-L1 or CD27 parental antibodies show no significant activity. In a mixed lymphocyte reaction assay, CDX-527 is more potent than the combination of the parental antibodies, suggesting that cross-linking through both Fc receptors and PD-L1 results in enhanced CD27 agonist activity. In human CD27 transgenic mice, we observed that antigen-specific T cell responses to a vaccine in vivo are significantly more enhanced with a surrogate CD27/PD-L1 bsAb than with either individual antibody. Furthermore, the surrogate bsAb exhibits greater antitumor activity than the combination of the parental antibodies in a syngeneic lymphoma model. Taken together, these results suggest that the enhanced activity of CDX-527 can be attributed to more efficient cross-linking of the bispecific antibody acting on the CD27 receptor, resulting in stronger T cell activation, combined with efficient PD-1/PD-L1 blockade, providing a novel approach to immunotherapy of cancers. We have initiated development activities for CDX-527 including a pilot study in cynomolgus macaques to investigate the PK and PD properties and provide guidance for the design of a GLP toxicology study.Citation Format: Laura A. Vitale, Lawrence J. Thomas, Thomas O'Neill, Jenifer Widger, Laura Mills-Chen, Andrea Crocker, Colleen Patterson, Anna Wasiuk, Eric Forsberg, James Boyer, Crystal Sisson, Jeffrey Weidlick, Shannon Renn-Bingham, Ioannis Papayannopoulos, Russ Hammond, Joel Goldstein, Henry C. Marsh, Tibor Keler, Li-Zhen He. CDX-527: A novel bispecific immune-modulating antibody targeting CD27 and PD-L1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2392.
Picosecond Imaging Circuit Analysis of Leakage Currents in CMOS Circuits (2002)

Abstract The light emission from ever increasing OFF-state leakage currents in advanced CMOS technologies can now be reliably measured using existing photon detectors. The measurements of such an emission provide valuable information about the operation of ICs. In this paper we suggest and experimentally confirm two new techniques based on such measurements - Transient Logic State Detection and Power Supply Noise Analysis.
Amino acid conjugated small molecule BLX-1002 lowers blood glucose in insulin resistant db/db and ob/ob mice and inhibits TNF-? , IL-6 cytokines (2004)

BLX-1002 is a water-soluble, orally active, modified single amino acid derivative with no structural resemblance with any existing compounds. When given orally in obese diabetic db/db or ob/ob mice, at a dose of 50 mg/kg body weight per day, it was able to reduce blood glucose by 30-40% compare to vehicle treated animals. Unlike other drugs, it reduced body weight gains in these animal models without any effect in food intake. BLX-1002 significantly lowered blood glycosylated hemoglobin ( 0.8%), free fatty acid (43%), triglyceride (20%) and total cholesterol (28%) levels compare to control group. In high fat diet model, BLX-1002 reduced body weight gain and significantly (p0.05) improved oral glucose tolerance.
Sculpting bespoke mountains: Determining free energies with basis expansions (2015)

The intriguing behavior of a wide variety of physical systems, ranging from amorphous solids or glasses to proteins, is a direct manifestation of underlying free energy landscapes riddled with local minima separated by large barriers. Exploring such landscapes has arguably become one of statistical physics's great challenges. A new method is proposed here for uniform sampling of rugged free energy surfaces. The method, which relies on special Green's functions to approximate the Dirac delta function, improves significantly on existing simulation techniques by providing a boundary-agnostic approach that is capable of mapping complex features in multidimensional free energy surfaces. The usefulness of the proposed approach is established in the context of a simple model glass former and model proteins, demonstrating improved convergence and accuracy over existing methods.
Chemical interactions between an active pharmaceutical ingredient and its counterion in a tromethamine salt under forced degradation conditions (2011)

In this study, the tromethamine salt of an active pharmaceutical ingredient containing both a carboxylic acid and ethyl ester functionality was subjected to forced degradation conditions. Based on HPLC-MS analysis, it was found that tromethamine formed both amide and ester type condensation products with the API, with amide formation predominating over ester formation. Addition of tromethamine at the carboxylic acid group of the API was favored over addition at the ethyl ester group. Tromethamine condensation products were observed only under the harshest stress conditions (80 degrees and 75% relative humidity), in which the salt physically changed from a crystalline form to a deliquesced state. Under stress conditions in which the crystalline structure of the salt remained intact, good stability was observed. Thus, the interaction between tromethamine and API occurred only in cases where the crystallinity of the salt was compromised.
In-die mask registration measurement on 28nm-node and beyond (2013)

As semiconductor go to smaller node, the critical dimension (CD) of process become more and more small. For lithography, RET (Resolution Enhancement Technology) applications can be used for wafer printing of smaller CD/pitch on 28nm node and beyond. SMO (Source Mask Optimization), DPT (Double Patterning Technology) and SADP (Self-Align Double Patterning) can provide lower k1 value for lithography. In another way, image placement error and overlay control also become more and more important for smaller chip size (advanced node). Mask registration (image placement error) and mask overlay are important factors to affect wafer overlay control/performance especially for DPT or SADP. In traditional method, the designed registration marks (cross type, square type) with larger CD were put into scribe-line of mask frame for registration and overlay measurement. However, these patterns are far way from real patterns. It does not show the registration of real pattern directly and is not a convincing method. In this study, the in-die (in-chip) registration measurement is introduced. We extract the dummy patterns that are close to main pattern from post-OPC (Optical Proximity Correction) gds by our desired rule and choose the patterns that distribute over whole mask uniformly. The convergence test shows 100 points measurement has a reliable result.
OTN Technology for Multi-flow Optical Transponder in Elastic 400G/1T Transmission Era (2012)

We study the multi-flow optical transponder from the viewpoint of OTN. Rate flexible OTU and multiplexing hierarchy for the elastic network are studied in detail and the required OTN standard extension is elucidated.
Synthesis of oxygenated metabolites of indeno[1,2,3-cd]pyrene (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of oxygenated metabolites of indeno[1,2,3-cd]pyreneJoseph E. Rice, Edmond J. LaVoie, Dan J. McCaustland, Daniel L. Fischer, and James C. Wiley Jr.Cite this: J. Org. Chem. 1986, 51, 13, 2428–2434Publication Date (Print):June 1, 1986Publication History Published online1 May 2002Published inissue 1 June 1986https://pubs.acs.org/doi/10.1021/jo00363a005https://doi.org/10.1021/jo00363a005research-articleACS PublicationsRequest reuse permissionsArticle Views488Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
[Elements for an analysis of psychosocial indicators and psychological intervention in heart transplantation]. (1988)

It is now accepted that cardiac transplantation is a viable therapeutic alternative for patients with end-stage heart disease. The most recent data offer a favourable short and medium term prognosis. Retrospective studies suggest that transplantation is associated with a good quality of life and tolerance of the side effects of the medication. Even if cardiac transplantation does not appear to be associated with serious psychological morbidity, it is important to assess the recipient's anxiety, depression, body image and his subjective quality of life, including satisfaction with his family and marital life, to prevent postoperative psychologic distress and enhance the patient's coping abilities. The family is the patient's chief buffer against stress but it is also under stress and needs to be aided through this process. The psychosocial themes that appear prominently at the different stages of the transplant process are somewhat predictable. These can be used to help the patient and family anticipate stress and deal with these issues in a way that enhances mastery of a difficult situation. The heart transplant team faces difficult ethical issues regarding patient selection and informed consent. Public input on these issues is needed, especially since more patients elect to receive heart transplants and the donor supply is likely to remain the same, thereby making donor hearts less available to those who could derive benefit from them.
<title>Designs to improve polysilicon micromirror surface topology</title> (1997)

Many applications for surface micromachined micromirrors require optically flat mirror surfaces. Holographic data storage and optical beam steering for display applications need reflective surfaces free of phase distortion to reduce the signal noise level, minimize cross-talk, and keep the system in focus. Typical micromirror designs may have unintentional embossing on the mirror surface resulting from the top surface conforming to the pattern of underlying layers. The bottom layers may have been shaped to form electrodes to electrostatically move the mirror. The mirror surface may also sag as a result of an imbalance between the stresses in the metal layer and the underlying polysilicon layer. This paper presents a study of the surface of a baseline micromirror, and shows the results of applying smart designs to minimize surface topology defects. The micromirrors presented in this paper were fabricated through the multi-user MEMS processes and categorized with an interferometric microscope.
A study on EUV reticle surface molecular contamination under different storage conditions in a HVM foundry fab (2017)

The prospect of EUVL (Extreme Ultraviolet Lithography) insertion into HVM (High Volume Manufacturing) has never been this promising. As technology is prepared for "lab to fab" transition, it becomes important to comprehend challenges associated with integrating EUVL infrastructure within existing high volume chip fabrication processes in a foundry fab. The existing 193nm optical lithography process flow for reticle handling and storage in a fab atmosphere is well established and in-fab reticle contamination concerns are mitigated with the reticle pellicle. However EUVL reticle pellicle is still under development and if available, may only provide protection against particles but not molecular contamination. HVM fab atmosphere is known to be contaminated with trace amounts of AMC’s (Atmospheric Molecular Contamination). If such contaminants are organic in nature and get absorbed on the reticle surface, EUV photon cause photo-dissociation resulting into carbon generation which is known to reduce multilayer reflectivity and also degrades exposure uniformity. Chemical diffusion and aggregation of other ions is also reported under the e-beam exposure of a EUV reticle which is known to cause haze issues in optical lithography. Therefore it becomes paramount to mitigate absorbed molecular contaminant concerns on EUVL reticle surface. In this paper, we have studied types of molecular contaminants that are absorbed on an EUVL reticle surface under HVM fab storage and handling conditions. Effect of storage conditions (gas purged vs atmospheric) in different storage pods (Dual pods, Reticle Clamshells) is evaluated. Absorption analysis is done both on ruthenium capping layer as well as TaBN absorber. Ru surface chemistry change as a result of storage is also studied. The efficacy of different reticle cleaning processes to remove absorbed contaminant is evaluated as well.
Extracellular vesicles and vesicle-free secretome of the protozoa Acanthamoeba castellanii under homeostasis and nutritional stress and their damaging potential to host cells (2018)

Acanthamoeba castellanii (Ac) are ubiquitously distributed in nature, and by contaminating medical devices such as heart valves and contact lenses, they cause a broad range of clinical presentations to humans. Although several molecules have been described to play a role in Ac pathogenesis, including parasite host-tissue invasion and escaping of host-defense, little information is available on their mechanisms of secretion. Herein, we describe the molecular components secreted by Ac, under different protein availability conditions to simulate host niches. Ac extracellular vesicles (EVs) were morphologically and biochemically characterized. Dynamic light scattering analysis of Ac EVs identified polydisperse populations, which correlated to electron microscopy measurements. High-performance thin liquid chromatography of Ac EVs identified phospholipids, steryl-esters, sterol and free-fatty acid, the last two also characterized by GC-MS. Secretome composition (EVs and EVs-free supernatants) was also determined and proteins biological functions classified. In peptone-yeast-glucose (PYG) medium, a total of 179 proteins were identified (21 common proteins, 89 exclusive of EVs and 69 in EVs-free supernatant). In glucose alone, 205 proteins were identified (134 in EVs, 14 common and 57 proteins in EVs-free supernatant). From those, stress response, oxidative and protein and amino acid metabolism proteins prevailed. Qualitative differences were observed on carbohydrate metabolism enzymes from Krebs cycle and pentose phosphate shunt. Serine proteases and metalloproteinases predominated. Analysis of the cytotoxicity of Ac EVs (upon uptake) and EVs-free supernatant to epithelial and glioblastoma cells revealed a dose-dependent effect. Therefore, the Ac secretome differs depending on nutrient conditions, and is also likely to vary during infection.
Metabolism of arachidonic acid in human lung cancer cell lines. (1987)

The metabolism of arachidonic acid (AA) was studied in two pulmonary bronchioloalveolar-carcinoma cell lines (NCI-H322 and NCI-H358) and two small cell lung carcinoma cell lines (NCI-H69 and NCI-H128). Exogenous AA was metabolized only in the NCI-H322 and NCI-H358 cells. There was no detectable metabolism of AA in NCI-H69 or NCI-H128 cells, either in the presence or the absence of the calcium ionophore A23187. The major metabolite of AA isolated from both NCI-H322 and NCI-H358 cells was prostaglandin E2 (PGE2). Prostaglandin endoperoxide synthase activities, expressed as immunoreactive PGE2 (pmol/min/mg protein), were 10.3 +/- 0.28 (SD) and 4.8 +/- 0.48 in NCI-H358 and NCI-H322 cells, respectively. The rate of production of PGE2 by both NCI-H358 and NCI-H322 cells was linear up to 10 min. Production of PGE2 in both cell lines was dependent upon substrate concentration and was maximal above 17 microM AA. Moreover, PGE2 did not undergo further metabolism by either the NCI-H358 or the NCI-H322 cells. Aspirin (0.1 mM), a cyclooxygenase inhibitor, decreased PGE2 production by 77 and 60% in NCI-H358 and NCI-H322 cells, respectively. In the presence of exogenous AA the calcium ionophore, A23187 (20 microM), stimulated PGE2 production in NCI-H322 cells by almost 2-fold, although it did not affect PGE2 production in the NCI-H358 cells. In contrast, A23187 stimulated the endogenous production of PGE2 in both NCI-H322 and NCI-H358 cells by 4- and 9-fold respectively. In addition, both the NCI-H358 and NCI-H322 cell lines were susceptible to the cytotoxic effects of the anticancer agent mitoxantrone in both a time and concentration dependent manner. In contrast, the two cell lines lacking detectable prostaglandin synthesis activity, NCI-H69 and NCI-H128 were unaffected by treatment with mitoxantrone. These results illustrate that there are major differences in the abilities of human lung cancer cell lines to biosynthesize and release PGE2. It is conceivable that such differences might have exploitable diagnostic and/or therapeutic implications.
Improving the Fit of Respiratory Face Masks through 3D Scanning, Finite Elements Analysis and Additive Manufacturing (2020)

The 2020 COVID-19 pandemic sheds a new light on the importance of wearing a mask to prevent virus propagation. A respiratory mask's efficiency is highly dependent on its adjustment with the face. With traditional face masks, achieving a perfect seal with the face proves to be challenging, even impossible without the aggressive tightening of its straps. Healthcare workers typically wear protective face masks for several consecutive hours, leading to discomfort, inflammation, or more serious injuries. This paper highlights how the combination of current technologies such as 3D scanning, Finite Element simulation, machine learning, and additive manufacturing offers a seamless workflow to generate a sterilizable, reusable and validated custom-fit mask.
Measurement of the W W + W Z cross section and limits on anomalous triple gauge couplings using final states with one lepton, missing transverse momentum, and two jets with the ATLAS detector at s = 7 $$ \sqrt{s}=7 $$ TeV (2015)

The production of a W boson decaying to e or in association with a W or Z boson decaying to two jets is studied using 4.6 fb -1 of proton-proton collision data at s = 7 TeV recorded with the ATLAS detector at the LHC. The combined W W +W Z cross section is measured with a significance of 3.4 and is found to be 687 (stat.)19 (syst.) pb, in agreement with the Standard Model expectation of 61.12.2 pb. The distribution of the transverse momentum of the dijet system is used to set limits on anomalous contributions to the triple gauge coupling vertices and on parameters of an effective-field-theory model.
Central Actions of Somatostatin-28 and Oligosomatostatin Agonists to Prevent Components of the Endocrine, Autonomic and Visceral Responses to Stress Through Interaction with Different Somatostatin Receptor Subtypes (2012)

Somatostatin was discovered four decades ago and since then its physiological role has been extensively investigated, first in relation with its inhibitory effect on growth hormone secretion but soon it expanded to extrapituitary actions influencing various stressresponsive systems. Somatostatin is expressed in distinct brain nuclei and binds to five somatostatin receptor subtypes which are also widely expressed in the brain with a distinct distribution pattern. The last few years witnessed the discovery of highly selective peptide somatostatin receptor agonists and antagonists representing valuable tools to delineate the respective pathways of somatostatin signaling. Here we review the centrally mediated actions of somatostatin and related selective somatostatin receptor subtype agonists to influence the endocrine, autonomic, and visceral components of the stress response and basal behavior as well as thermogenesis.
TEMPO/Viologen Electrochemical Heterojunction for Diffusion-Controlled Redox Mediation: A Highly Rectifying Bilayer-Sandwiched Device Based on Cross-Reaction at the Interface between Dissimilar Redox Polymers (2014)

A couple of totally reversible redox-active molecules, which are different in redox potentials, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and viologen (V(2+)), were employed to give rise to a rectified redox conduction effect. Single-layer and bilayer devices were fabricated using polymers containing these sites as pendant groups per repeating unit. The devices were obtained by sandwiching the redox polymer layer(s) with indium tin oxide (ITO)/glass and Pt foil electrodes. Electrochemical measurements of the single-layer device composed of polynorbornene-bearing TEMPO (PTNB) exhibited a diffusion-limited current-voltage response based on the TEMPO(+)/TEMPO exchange reaction, which was almost equivalent to a redox gradient through the PTNB layer depending upon the thickness. The bilayer device gave rise to the current rectification because of the thermodynamically favored cross-reaction between TEMPO(+) and V(+) at the polymer/polymer interface. A current-voltage response obtained for the bilayer device demonstrated a two-step diffusion-limited current behavior as a result of the concurrent V(2+)/V(+) and V(+)/V(0) exchange reactions according to the voltage and suggested that the charge transport process through the device was most likely to be rate-determined by a redox gradient in the polymer layer. Current collection experiments revealed a charge transport balance throughout the device, as a result of the electrochemical stability and robustness of the polymers in both redox states.