gebhart/patrepeval huggingface dataset:
Sym021, a promising anti-PD1 clinical candidate antibody derived from a new chicken antibody discovery platform (2019)

Discovery of therapeutic antibodies is a field of intense development, where immunization of rodents remains a major source of antibody candidates. However, high orthologue protein sequence homology between human and rodent species disfavors generation of antibodies against functionally conserved binding epitopes. Chickens are phylogenetically distant from mammals. Since chickens generate antibodies from a restricted set of germline genes, the possibility of adapting the Symplex antibody discovery platform to chicken immunoglobulin genes and combining it with high-throughput humanization of antibody frameworks by "mass complementarity-determining region grafting" was explored. Hence, wild type chickens were immunized with an immune checkpoint inhibitor programmed cell death 1 (PD1) antigen, and a repertoire of 144 antibodies was generated. The PD1 antibody repertoire was successfully humanized, and we found that most humanized antibodies retained affinity largely similar to that of the parental chicken antibodies. The lead antibody Sym021 blocked PD-L1 and PD-L2 ligand binding, resulting in elevated T-cell cytokine production in vitro. Detailed epitope mapping showed that the epitope recognized by Sym021 was unique compared to the clinically approved PD1 antibodies pembrolizumab and nivolumab. Moreover, Sym021 bound human PD1 with a stronger affinity (30 pM) compared to nivolumab and pembrolizumab, while also cross-reacting with cynomolgus and mouse PD1. This enabled direct testing of Sym021 in the syngeneic mouse in vivo cancer models and evaluation of preclinical toxicology in cynomolgus monkeys. Preclinical in vivo evaluation in various murine and human tumor models demonstrated a pronounced anti-tumor effect of Sym021, supporting its current evaluation in a Phase 1 clinical trial. Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CDR, complementarity determining region; DC, dendritic cell; ELISA, enzyme-linked immunosorbent assay; FACS, fluorescence activated cell sorting; FR, framework region; GM-CSF, granulocyte-macrophage colony-stimulating factor; HRP, horseradish peroxidase; IgG, immunoglobulin G; IL, interleukin; IFN, interferon; mAb, monoclonal antibody; MLR, mixed lymphocyte reaction; NK, natural killer; PBMC, peripheral blood mono-nuclear cell; PD1, programmed cell death 1; PDL1, programmed cell death ligand 1; RT-PCR, reverse transcription polymerase chain reaction; SEB, Staphylococcus Enterotoxin B; SPR, surface Plasmon Resonance; VL, variable part of light chain; VH, variable part of heavy chain.
&lt;title&gt;Brief history of vector Doppler&lt;/title&gt; (2001)

Since the development of the directional Doppler by McLeod in 1967, methods of acquiring, analyzing, and displaying blood velocity information have been under constant exploration. These efforts are motivated by a variety of interest and objectives including, to: a) simplify clinical examination, examiner training, and study interpretation, b) provide more hemodynamic information, and c) reduce examination variability and improve accuracy. The vector Doppler technique has been proposed as one potential avenue to achieve these objects. Vector Doppler systems are those that determine the true 2D or 3D blood flow velocity by combining multiple independent velocity component measurements. Most instruments can be divided into two broad categories: 1) cross-beam and 2) time-domain. This paper provides a brief synopsis of the progression of vector Doppler techniques, from its onset in 1970 to present, as well as possible avenues for future work. This is not intended to be a comprehensive review of all vector Doppler systems.
High modulus steels: new requirement of automotive market. How to take up challenge? (2014)

Since the last decade, lightening of automotive structure was mainly achieved by gauge reduction using ultrahigh strength steels such as dual phase and transformation induced plasticity grades. However, gauge reduction can significantly reduce the stiffness. Limits are today reached for some applications such as chassis/suspension part. Development of steel with improved specific stiffness becomes more and more relevant to go further in weight reduction. Development of steel matrix composites (SMCs) with ceramic reinforcements is a promising solution. With an appropriate selection of the ceramic, eutectic solidification can be achieved. This natural production route guarantees a good cohesion of the steel/reinforcement interface and the control of the main parameters, which provide final properties of the product (size, shape, clustering of reinforcement). Significant fraction of ceramic can be obtained (10–25 vol.-%). Eutectic SMC can be produced with conventional industrial process such as continuous casting and hot strip mill which guarantees high productivity and low cost.Depuis la dernière décennie, l’allègement des structures automobiles a été réalisé en grande partie par la réduction des épaisseurs au travers l’utilisation d’aciers à très haute résistance tels que les aciers DP (biphasés) et TRIP (à plasticité induite par transformation). Cependant, cette réduction des épaisseurs peut entraîner une baisse de rigidité. Aujourd’hui, les limites ont été atteintes pour certaines applications telles que les composantes châssis et suspension. Le développement d’acier à rigidité spécifique améliorée devient une voie de développement de plus en plus pertinente pour progresser dans la réduction de poids. Le développement de composites à matrice d’acier et renfort céramique est une solution prometteuse. Au travers d’une sélection appropriée de la céramique, on peut obtenir une solidification eutectique. Cette route naturelle de production des aciers garantit une bonne cohésion de l’interface acier/renfort ainsi que la maîtrise des principaux paramètres qui contrôlent les propriétés finales du produit (taille, forme, agglomération du renfort). Des fractions significatives de renfort céramique peuvent être atteintes (10–25% en volume). Les composites à matrice métallique (CMM) eutectique peuvent être élaborés par des procédés industriels conventionnels tels que la coulée continue ou le laminage à chaud qui garantissent une productivité élevée et un faible coût.
Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge (2014)

The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2×106 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis.
Uncertainty quantification for discrimination of nuclear events as violations of the comprehensive nuclear-test-ban treaty (2016)

Enforcement of the Comprehensive Nuclear Test Ban Treaty (CTBT) will involve monitoring for radiologic indicators of underground nuclear explosions (UNEs). A UNE produces a variety of radioisotopes which then decay through connected radionuclide chains. A particular species of interest is xenon, namely the four isotopes (131m)Xe, (133m)Xe, (133)Xe, and (135)Xe. Due to their half lives, some of these isotopes can exist in the subsurface for more than 100 days. This convenient timescale, combined with modern detection capabilities, makes the xenon family a desirable candidate for UNE detection. Ratios of these isotopes as a function of time have been studied in the past for distinguishing nuclear explosions from civilian nuclear applications. However, the initial yields from UNEs have been treated as fixed values. In reality, these independent yields are uncertain to a large degree. This study quantifies the uncertainty in xenon ratios as a result of these uncertain initial conditions to better bound the values that xenon ratios can assume. We have successfully used a combination of analytical and sampling based statistical methods to reliably bound xenon isotopic ratios. We have also conducted a sensitivity analysis and found that xenon isotopic ratios are primarily sensitive to only a few of many uncertain initial conditions.
DarkFocus: numerical autofocusing in digital in-line holographic microscopy using variance of computational dark-field gradient (2020)

We report on a novel computational technique for automatic numerical refocusing in digital in-line holographic microscopy. It is based on the adaptive filtering of the recorded on-axis hologram to eliminate its background term and extract interference intensity-component connected with light scattered on the sample (interference fringes). Numerical propagation of such filtered hologram yields the computationally generated dark-field imaging coming from the amplitude part of the complex field. We propose a simple measure in the form of the variance of the dark-field gradient, which attains its maximum value in the focal planes for all types of objects (phase, amplitude and mixed phase-amplitude), as a robust indicator of overall sharpness and in-focus quality. Demonstrated novel autofocusing technique is positively validated using experimental data exhibiting significant variation of the magnification factor for both single and double focal plane scenarios. It compares favorably with other well-established automatic numerical refocusing techniques based on the high-pass filtered complex amplitude and edge sparsity, mainly in terms of higher axial resolution and better robustness to hologram low signal-to-noise ratio.
Silyl glyoxylates as high‐performance photoinitiators for cationic and hybrid polymerizations: Towards better polymer mechanical properties (2019)

ABSTRACT Silyl glyoxylates are proposed here as high‐performance photoinitiators (PIs) for the hybrid polymerization of cationic and radical monomers. Recently, silyl glyoxylates were reported as a new class of high‐performance Type I photoinitiators for free radical polymerization under air upon exposure to different near‐UV and blue LEDs. In this article, we report this new class of photoinitiators to initiate cationic polymerization in combination with an iodonium salt. This system can also be used to initiate simultaneously free radical and cationic polymerizations, for example, for the free radical/cationic hybrid polymerization and for the synthesis of interpenetrating polymer networks. The system silyl glyoxylate/iodonium exhibits excellent polymerization performances and exceptional bleaching properties compared to other well established photoinitiators (e.g., camphorquinone). Furthermore, a hybrid monomer is also introduced in this article (2‐vinyloxyethoxyethyl methacrylate [VEEM]) leading to a huge improvement of the mechanical properties of the final polymer through hybrid polymerization. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1420–1429
Dynamosaicing: Mosaicing of Dynamic Scenes (2007)

This paper explores the manipulation of time in video editing, enabling to control the chronological time of events. These time manipulations include slowing down (or postponing) some dynamic events while speeding up (or advancing) others. When a video camera scans a scene, aligning all the events to a single time interval will result in a panoramic movie. Time manipulations are obtained by first constructing an aligned space-time volume from the input video, and then sweeping a continuous 2D slice (time front) through that volume, generating a new sequence of images. For dynamic scenes, aligning the input video frames poses an important challenge. We propose to align dynamic scenes using a new notion of "dynamics constancy", which is more appropriate for this task than the traditional assumption of "brightness constancy". Another challenge is to avoid visual seams inside moving objects and other visual artifacts resulting from sweeping the space-time volumes with time fronts of arbitrary geometry. To avoid such artifacts, we formulate the problem of finding optimal time front geometry as one of finding a minimal cut in a 4D graph, and solve it using max-flow methods.
Hemoglobin Decline During Lead-in Phase as an Early Predictor of Anemia After the Addition of Boceprevir: A Retrospective Analysis of HCV SPRINT-1 (2010)

Background. SPRINT-1 is a Phase 2b trial of 595 treatment-naive patients to assess the safety and efficacy of boceprevir (BOC) 800 mg TID, an oral inhibitor of HCV-NS3 protease, plus standard of care peginterferon alfa-2b 1.5 mcg/kg/week (P) and ribavirin 400-1400 mg/day (R) compared to P/R alone in genotype 1 (G1) chronic hepatitis C (CHC) patients. Two of the study arms received P/R for 4 wks (lead-in) prior to adding BOC. R therapy is well known to decrease hemoglobin (Hgb) and addition of BOC can further decrease Hgb by 1-1.5 g/dL. The aim of this analysis was to assess the predictive value of the Hgb decline during P/R leadin for the Hgb nadir after addition of BOC. Methods. Patients were randomized to 48 wks of P/R or 4 wks of P/R lead-in followed by P/R/BOC for 24 or 44 wks or P/R/BOC for 28 or 48 wks. The primary endpoint was SVR at 24 wks post-treatment (Roche TaqMan LLD<15 IU/mL). Hgb <10 g/dL was managed using protocol guidelines for R dose reduction. At the discretion of the investigator, erythropoietin (EPO) was also permitted with concomitant R dose reduction. Data from patients randomized to the 2 study arms with 4-wk P/R lead-in treatment were pooled for analysis. Results. Hgb nadirs were comparable in the 2 arms with 4 wk lead-in therapy, regardless of total treatment duration. Hgb nadir of <9.5 g/dL was observed in 27%29% of patients. The magnitude of Hgb decline during the P/R lead-in period correlated with the Hgb nadir observed after addition of BOC to the P/R treatment regimen (Table). Of all the patients from the 2 arms, 17% (31/183) had Hgb <10 g/dL by TW8 and 17% received EPO by TW8. In patients with ≥3g/dL decline of Hgb within the first 4 wks of lead-in, the Hgb nadir was <10g/dL in 61% (20/33) by TW8 and 67% (22/33) were treated with EPO by TW8. Conclusions. P/R lead-in therapy can identify patients at risk for further declines in Hgb after the addition of BOC to the treatment regimen. Such patients may benefit from close monitoring to prevent delays in the start of EPO treatment, reductions of R dosages to ineffective levels or discontinuation of therapy for anemia. A large clinical trial evaluating the role of EPO in the management of anemia during BOC therapy is ongoing and will provide additional information.
HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System (2018)

The primate lentiviral accessory protein Nef downregulates CD4 and major histocompatibility complex class I (MHC-I) from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison to CD4 and MHC-I. We confirm that Nef excludes Ser5 from human immunodeficiency virus type 1 (HIV-1) virions by downregulating its cell surface expression via similar functional motifs required for CD4 downregulation. We find that Nef decreases both Ser5 and CD4 expression at steady-state levels, which are rescued by NH<sub>4</sub>Cl or bafilomycin A1 treatment. Nef binding to Ser5 was detected in living cells using a bimolecular fluorescence complementation assay, where Nef membrane association is required for interaction. In addition, Nef triggers rapid Ser5 internalization via receptor-mediated endocytosis and relocalizes Ser5 to Rab5<sup>+</sup> early, Rab7<sup>+</sup> late, and Rab11<sup>+</sup> recycling endosomes. Manipulation of AP-2, Rab5, Rab7, and Rab11 expression levels affects the Nef-dependent Ser5 and CD4 downregulation. Moreover, although Nef does not promote Ser5 polyubiquitination, Ser5 downregulation relies on the ubiquitination pathway, and both K48- and K63-specific ubiquitin linkages are required for the downregulation. Finally, Nef promotes Ser5 colocalization with LAMP1, which is enhanced by bafilomycin A1 treatment, suggesting that Ser5 is targeted to lysosomes for destruction. We conclude that Nef uses a similar mechanism to downregulate Ser5 and CD4, which sorts Ser5 into a point-of-no-return degradative pathway to counteract its restriction.<b>IMPORTANCE</b> Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express an accessory protein called Nef to promote viral pathogenesis. Nef drives immune escape <i>in vivo</i> through downregulation of CD4 and MHC-I from the host cell surface. Recently, Nef was reported to counteract a novel host restriction factor, Ser5, to increase viral infectivity. Nef downregulates cell surface Ser5, thus preventing its incorporation into virus particles, resulting in disruption of its antiviral activity. Here, we report mechanistic studies of Nef-mediated Ser5 downregulation in comparison to CD4 and MHC-I. We demonstrate that Nef binds directly to Ser5 in living cells and that Nef-Ser5 interaction requires Nef association with the plasma membrane. Subsequently, Nef internalizes Ser5 from the plasma membrane via receptor-mediated endocytosis, and targets ubiquitinated Ser5 to endosomes and lysosomes for destruction. Collectively, these results provide new insights into our ongoing understanding of the Nef-Ser5 arms race in HIV-1 infection.
Genes for Developmental Fruit Coloration of Acorn Squash (1997)

Table Queen, an old cultivar of the acorn group of Cucurbita pepo, has fruits that are light green when young that become dark green by intermediate age and remain dark green through maturity. in order to determine the genetic basis of its devel opmental fruit color, Table Queen was crossed with three accessions of known genotype, Mgetabte Spaghettl (d/d l-1/l–1 l–2/l–2), Fordhook Zucchini (D/D L-1/L-1 L-2/L-2), and 85k–9–107–2 (d/d l-1/l-1 L-2/L-2). The progenies were observed and scored for fruit coloration at three developmental stages: young [2–5 days past anthesis (dpa)], intermediate (15–18 dpa), and mature (40–44 dpa). The results indicate that Table Queen possesses genotype D/D L-1/L-1 L/2/L-2. All of the accessions crossed with Table Queen carry two recessive genes, herein designated mature orange-1 (mo-1) and mature orange-2 (mo-2). The combination of these two recessive genes results in complete loss of green fruit color prior to maturity, except in L-1/-L-2/—plants. Table Queen fruits retain their green color through maturity because this cultivar carries the dominant alleles Mo-1 and Mo-2, either of which acting alone results in green color retention. Genes D and mo-2 are linked, approximately 15 map units apart.
Beam Dynamics for a High Current 3 MeV, 325 MHz Ladder-RFQ (2017)

After the successful measurements with a 0.8 m prototype (see Fig. 1), a 3.3 m Ladder-RFQ is under construction at IAP, Goethe University Frankfurt. It is designed to accelerate protons from 95 keV to 3 MeV according to the design parameters of the Proton Linac at FAIR. The development of an adequate beam dynamics design was done in close collaboration with the IAP resonator design team. A constant vane curvature radius and at the same time a flat voltage distribution along the RFQ was reached by implantation of the modulated vane geometry into CST Microwave Studio RF field simulations. Points of reference for the beam dynamics layout are the beam dynamics designs of C. Zhang* and A. Lombardi**. The Code RFQGen*** was used for the beam dynamics simulations. In order to increase the transmission and to reduce the longitudinal and transversal exit emittances, the evolution of the modulation parameter m within the first 90 cells was investigated in detail. This paper presents the simulation results of this study.
Traffic diffusion analysis for adaptive multi-path routing algorithm in sensor networks (2005)

Multipath routing algorithms in sensor networks provide extensive scope for adaptively routing and dispersing traffic over the network. An essential requirement for adaptive routing in sensor networks is to account for the high cost associated with the use of battery power and network bandwidth. In this paper, we propose an adaptive multi-path routing algorithm (AMRA) that diffuses the traffic such that energy consumption in minimized. We define a Hamiltonian as a function of the cost incurred and the benefit obtained by a node for forwarding packets. The Hamiltonian is then subjected to Pontryagin's cost minimization for efficiently diffusing the packets among the next-hop nodes. This traffic diffusion is computed by solving the steady state queue length equation which we represent in the frequency domain, ns-2 based simulation experiments are conducted and the performance of the proposed algorithm is compared against the AODV routing protocol.
Characterization and tuning of ultrahigh gradient permanent magnet quadrupoles (2009)

The application of quadrupole devices with high field gradients and small apertures requires precise control over higher order multipole field components. We present a new scheme for performance control and tuning, which allows the illumination of most of the quadrupole device aperture because of the reduction of higher order field components. Consequently, the size of the aperture can be minimized to match the beam size achieving field gradients of up to $500\text{ }\text{ }\mathrm{T}\text{ }{\mathrm{m}}^{\ensuremath{-}1}$ at good imaging quality. The characterization method based on a Hall probe measurement and a Fourier analysis was confirmed using the high quality electron beam at the Mainz Microtron MAMI.
Evolution of zoom lens optical design technology and manufacture (2021)

Zoom lenses have greatly improved to the extent that today many major performance characteristics are now equal to or come close to matching those of fixed focal length lenses. Some of these characteristics including size, weight, cost, producibility and general image performance are dependent on widely differing technologies. For example, optical design, coatings, refractive materials, surface types and the use of computers with suitable optical design software are just some of the technologies that when combined have driven the continuous development of zoom lenses and their optical designs.