gebhart/patrepeval huggingface dataset:
Fab-arm exchange (2012)

Immunology and structural biology are highly complex fields of study in which mechanisms and inter-relationships are often not easily understood. It is therefore quite common to use metaphors to make knowledge gained accessible to experts and non-experts alike. Thus we, for example, all know the antibody as a Y-shaped protein with two arms and a tail and we understand the specificity of antibody-antigen binding as a key-into-lock interaction. Are these metaphors strictly correct? No, of course not. Nevertheless, they are well-recognized and serve to provide some immediate and general understanding of key features.

When faced with the challenge of designing a simple descriptor or metaphor for the process leading to the exchange of human IgG4 “half-molecules,” we discussed various options with experts in the field and came up with the term “Fab-arm exchange.”1 The phrase is simply meant to highlight the functional consequence of this mechanism, i.e., the exchange of antigen-binding parts between parental antibody molecules leading to novel binding combinations in the product.

Professor Pandey argues in his letter that Fab-arm exchange is a misnomer and should be changed to IgG4-arm exchange with the argument that allotypic differences are ignored.2 Apart from the fact that, seen from Pandey’s view, the phrase IgG4-arm exchange suffers from similar weaknesses as the original (and should be termed IgG4-arm-and-tail exchange instead), clearly we disagree. This is not only in view of the above, but also due to the observation that Fab-arm exchange occurs in many animals involving distinct non-IgG4 antibody subclasses.3-5 In addition, we are obliged to point out that Pandey uses a weak example. Neither the V309/L309 nor the K409/R409 isoallotype6 are likely to have a functional impact on the product. Thus, we have demonstrated in Labrijn et al.,3 that K409 abrogates Fab-arm exchange for human IgG4 molecules and the exchange between isoallotypes in individuals carrying both genes therefore cannot occur. The formation of V309-L309 IgG4 heterodimers, in our view, has limited relevance as there is no indication in the literature that the isoallotype at this position affects antibody function.

In fact, Pandey might have found a better argument outside of the field of IgG allotypes. Differences in Fc-associated carbohydrates, for example, may affect antibody effector function or half-life7,8 and this therefore represents an example where the exchange of (half) Fc domains between antibody molecules might affect activity of the product. Nevertheless, we also believe that such exchange will not have significant functional consequences in a polyclonal response in vivo because of the dynamic recombination of these modifications with random antigen-binding specificities.

In summary, the reassortment of antigen-binding specificities is the major functional consequence of Fab-arm exchange and that’s in the name.
Broadening the Bandwidth of Electrically Small Antennas using Multi-Mode Synthesis (2008)

Traditional broadband antenna designs with compact radiating elements often explores the multiple resonant modes existing in the designed physical structure to obtain more bandwidth, or say to decrease the quality factor. It is well-known that antenna arrays could support multiple radiation modes. Recently, the modes in a coupled antenna system have been explored for MIMO and for beam-forming applications in a compact radiation platform. The underlying physical principle is taking the advantage of the collocated and orthogonal radiation pattern modes. Those modes in a compact radiation space could be isolated with each other after the mode-decomposition network. To maximize the bandwidth of the mode-decoupled antenna array, a systematic approach is proposed to enlarge the bandwidth electrically small antennas of the broadband array. Different from traditional antenna array design whose objective is usually to combine the antenna gain, the approach proposed here is to synthesize a broader bandwidth in the desired frequency range either in a few discrete band or one continuous band. The approach can be directly applied to electrically small antennas to achieve the maximum bandwidth available out of a small form factor platform. Electrically small antennas often utilize wire structures to explore lower quality factor and hence higher bandwidth. It has also been discussed that folded-arm spherical helical antennas exhibit an omni-directional, linearly polarized radiation pattern consistent with that of an electrical dipole.
Synthesis of 2-Acetamido-2-deoxy-β-d-glucopyranoseO-Glycopeptides fromN-Dithiasuccinoyl-Protected Derivatives1-3 (1996)

2-Acetamido-2-deoxy-β-d-glucopyranose (β-d-GlcpNAc), in O-glycosidic linkage to the side chain hydroxyls of serine (Ser) and threonine (Thr) residues, is often found in nuclear and cytoplasmic proteins. The “active ester” approach for solid phase glycopeptide synthesis calls for the direct glycosylation of Nα-(9-fluorenylmethyloxycarbonyl)amino acid pentafluorophenyl esters (Nα-Fmoc-AA-OPfp's). The synthesis of the required Ser(β-d-GlcpNAc) and Thr(β-d-GlcpNAc) building blocks poses special problems arising from the 2-amino substituent in the corresponding glycosyl donors. Activation of donors with a 2-N-acyl group provides relatively unreactive oxazoline intermediates, whereas the otherwise promising phthaloyl (Phth) group requires prolonged base treatment at elevated temperatures for its removal, and incomplete deprotection is often encountered. The dithiasuccinoyl (Dts) group provides bivalent protection in the same way as the Phth group, but has the advantage of being removed rapidly under mild conditions by thiolysis or other reductive procedures. The novel donor 3,4,6-tri-O-acetyl-2-deoxy-2-(dithiasuccinoylamino)-d-glucopyranosyl bromide (8) was prepared from d-glucosamine in four steps and overall 58% yield; this compound served for the fast and efficient glycosylation of Nα-Fmoc-Ser-OPfp and Nα-Fmoc-Thr-OPfp. The resultant glycosylated building blocks Nα-Fmoc-Ser(Ac3-β-d-GlcpNDts)-OPfp (9) and Nα-Fmoc-Thr(Ac3-β-d-GlcpNDts)-OPfp (10) were applied in the solid phase synthesis of several glycopeptides. Following incorporation of the glycosylated residue, the Dts function was removed quantitatively by thiolysis, the resultant free 2-amino group was acetylated, and stepwise chain elongation by Fmoc chemistry continued. Alternatively, it was possible to achieve selective Dts removal from 9 and 10 (without affecting the Pfp ester) by reduction with zinc under acidic conditions; in situ acetylation of the exposed amine provided the alternative building blocks Nα-Fmoc-Ser(Ac3-β-d-GlcpNAc)-OPfp (11) and Nα-Fmoc-Thr(Ac3-β-d-GlcpNAc)-OPfp (12).
Supplementary Figure 4 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection (2023)

&lt;p&gt;PDF file - 3477K, Effect of surgery on cellular activation markers. Pre-surgical (time point zero) and post-surgical (at designated weeks after surgery) measurements on the same patients are connected by a line and the statistical significance is calculated by a paired Wilcoxon rank-sum test. Data points from stage 4 patients are marked with black filled diamonds and the data from the single stage 3 patient is shown in grey. Sub-panels are as follows: A) CD69 on T Cells (CD3+ CD45+ CD56-), B) Perforin in CD8+ T Cells, C) Granzyme B in CD8+ T Cells, D) Perforin in CD4+ T Cells, E) Granzyme B in CD56dim NK Cells, F) Perforin in CD56dim NK Cells.&lt;/p&gt;
Enhanced Spin Interactions in Digital Magnetic Heterostructures (1995)

A new heterostructure is developed in which fractional monolayers of magnetic ions are introduced ``digitally'' within a semiconductor quantum well. Rearranging moments within two-dimensional (2D) planes provides additional control over their interactions, yielding tunable two-level electronic systems in which spin splittings are significantly larger than inhomogeneous linewidths in modest magnetic fields. Femtosecond-resolved electronic and magnetic spectroscopies reveal spin-flip scattering dependent only on the Zeeman energy but not the local magnetic environment, and long-lived dynamic magnetizations.
Analysis of Gene Expression Data (2005)

This chapter contains sections titled: Data Capture DNA Array Platforms Image Analysis and Data Quality Control Grid Finding Quantification of Signal Intensities Signal Validity Pre-processing Global Measures Linear Model Approaches Nonlinear and Spatial Effects Other Approaches Fold-change Analysis Planning and Designing Experiments Tests for Differential Expression Multiple Testing ROC Curve Analysis Validation Methods Clustering Algorithms Hierarchical Clustering Self-organizing Maps (SOMs) K-means Validation of Gene Expression Data Cluster Validation Principal Component Analysis Functional Categorization Classification Methods Basic Concepts Support Vector Machines Other Approaches Cross-validation The Holdout Method k-fold Cross-validation Leave-one-out Cross-validation Reverse Engineering Genetic Networks Reconstructing Boolean Networks Other Approaches Network Motifs
Supplementary material from "Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair" (2017)

Mechanical stress is one of the major aetiological factors underlying soft-tissue remodelling, especially for the mitral valve (MV). It has been hypothesized that altered MV tissue stress states lead to deviations from cellular homeostasis, resulting in subsequent cellular activation and extracellular matrix (ECM) remodelling. However, a quantitative link between alterations in the organ-level <i>in vivo</i> state and <i>in vitro</i>-based mechano-biology studies has yet to be made. We thus developed an integrated experimental–computational approach to elucidate MV tissue and interstitial cell responses to varying tissue strain levels. Comprehensive results at different length scales revealed that normal responses are observed only within a defined range of tissue deformations, whereas deformations outside of this range lead to hypo- and hyper-synthetic responses, evidenced by changes in α-smooth muscle actin, type I collagen, and other ECM and cell adhesion molecule regulation. We identified MV interstitial cell deformation as a key player in leaflet tissue homeostatic regulation and, as such, used it as the metric that makes the critical link between <i>in vitro</i> responses to simulated equivalent <i>in vivo</i> behaviour. Results indicated that cell responses have a delimited range of <i>in vivo</i> deformations that maintain a homeostatic response, suggesting that deviations from this range may lead to deleterious tissue remodelling and failure.
Effective incorporation of biospecimen collection for translational studies into a phase III trial: The NeoALTTO experience (BIG 01-06). (2013)

3012 Background: Translational research studies in the context of clinical trials using targeted therapies are essential for the identification of biomarkers of response or resistance. However, many challenges (e.g. logistic, technical) can impede proper biological sample collection. The NEOALTTO study provided an excellent opportunity to address these issues. Methods: In this large neoadjuvant phase III multicenter, multinational clinical trial, serial samples (plasma, serum, frozen and FFPE specimens) from patients with breast cancer were collected in 86 sites (23 countries) at several time points (baseline, week 2 and surgery). Standardized operating procedures were made available to sites together with pre-assembled kits for sample collection, processing, storage, and shipment to reduce the variability and increase compliance with the study protocol. All biospecimens were centralized for long term storage. Baseline fresh/frozen samples were processed for downstream analyses according to a pre-defined workflow. Evaluable sample population (ESP) was determined based on the following criteria: tumor cellularity, RNA integrity (RIN), and yield. Results: A total of 12,193 serial samples from 449 of 455 randomized patients was collected. The overall sample missing rate was 9.5% (includes samples not collected by site, withdrawn patients and pCR). Missing rates were 9%, 8%, 13%, and 9% for plasma, serum, frozen and FFPE specimens, respectively. At least 1 frozen tumor tissue was available for 423 (94%), 431 (96%), and 334 (74%) patients at baseline, week 2, and surgery, respectively. After 2 extraction cycles, 629 and 516 baseline frozen samples were processed for RNA and DNA extraction, respectively. The ESP was 71% (58% when RIN considered) and 80% for downstream RNA- and DNA-based analyses, respectively. Incorrect material, inappropriate sample processing and low or absent tumor cellularity were some of the factors affecting the ESP. Conclusions: These results show that careful upfront logistic and technical planning in NEOALTTO had a significant impact on the compliance and the quality of collected material, which may ultimately result in valuable research data. Clinical trial information: NCT00553358.
Effect of murine recombinant interleukin‐5 on the cell population in guinea‐pig airways (1992)

1. An intratracheal injection of murine recombinant interleukin 5 (mrIL-5, 2-15 microgram/0.25 ml/animal) induced a dose-dependent increase in the number of macrophages, eosinophils, neutrophils and epithelial cells in the bronchoalveolar lavage fluid (BALF) of guinea-pigs 24 h after administration. Bovine serum albumin (15 micrograms/0.25 ml/animal), used as a reference material, did not cause any change of this type. 2. The intratracheal administration of mrIL-5 at a dose of 15 microgram showed a tendency to increase the number of these pulmonary inflammatory cells and epithelial cells in the BALF at 12 h with a significant increase observed at 24 h. 3. Prednisolone (20 mg kg-1, i.p.) inhibited the mrIL-5-induced increase in macrophages, eosinophils, neutrophils and epithelial cells. Ketotifen (2 mg kg-1, i.p.) reduced the mrIL-5-induced increase in the eosinophil, neutrophil and epithelial cell populations. The simultaneous injection of 2% disodium cromoglycate (DSCG) into the trachea prevented the mrIL-5-induced increase in the number of airway epithelial cells, without affecting changes in the other inflammatory leukocytes. 4. These results suggest that mrIL-5 is a potent inducer of lung inflammation, in terms of increased inflammatory leukocytes and epithelial cells in guinea-pig BALF. Prednisolone, DSCG and ketotifen are effective against mrIL-5-induced pulmonary inflammation, especially the desquamation of bronchial epithelial cells.
Identification of a male‐specific histocompatibility protein on preimplantation porcine embryos (1987)

An indirect immunofluorescence assay was used to detect the presence of male-specific protein(s) on various stages of preimplantation porcine embryos. Embryos were collected at slaughter from the reproductive tracts of day-2.5, -4, -5, -6, and -8 (day 0 = first day of estrus) sows and gilts. Embryos were placed in medium containing an anti-male primary antibody, washed, and transferred to culture drops containing a fluorescein isothiocyanate (FITC)-labeled secondary antibody. Embryos were classified as either fluorescent (H-Y positive) or nonfluorescent (H-Y negative), transferred to coded drops, and karyotyped to examine sex chromosomes. A total of 91 eight-cell to blastocyst stage embryos were evaluated; of these, 46% were classified as fluorescent and 54% as nonfluorescent. Of readable metaphase spreads (65%) from these embryos, 81% (48 of 59, P less than 0.005) were correctly sexed by immunological detection of the male-specific antigen. Although 13% (2/15) of four-cell embryos evaluated were classified as fluorescent, the accuracy with which embryos at this stage were sexed by detection of H-Y antigen was not different from 50%. Fifty percent of eight-cell embryos were classified as H-Y positive with 78% of embryos correctly sexed. It was concluded that the eight-cell embryo is the earliest stage of development for which there is evidence for expression of H-Y antigen. Detection of the male-specific protein was difficult at the expanded blastocyst stage.
Synthesis and Molecular Modeling Studies on Novel C2 Alkylated Benzoazonine Scaffold and Corresponding 2-Pyrazoline Derivatives as Acetylcholinestrase Enzyme Inhibitors (2019)

A rapid and efficient methodology was performed for the synthesis of α,β-unsaturated ketones 2a–k containing benzoazonine core through Claisen-Schmidt reaction of the benzoazonine-2,7-dione 1 and various aldehydes in acidic medium. The obtained exocyclic α,β-unsaturated ketones were subjected to an irradiating microwave gave unexpected asymmetric spiro pyran compound 3 via a self-Diels–Alder reaction. The initially formed exocyclic α,β-unsaturated ketones underwent cyclocondesation with phenylhydrazine to afford 2-pyrazoline derivatives 4. The structure of the synthesized scaffolds was characterized using 1H-NMR, APT and 2DNMR spectra. A molecular modeling study using Molecular Operating Environment was performed to investigate their binding modes to the Acetylcholinestrase enzyme active site. Docking results demonstrated that the newly synthesized compounds recognized the active sites of Acetylcholinestrase and form different types of bonding interactions with key active site amino acid residues.
Effects of Surface Waviness on Fan Blade Boundary Layer Transition and Profile Loss—Part I: Methodology and Computational Results (2021)

Abstract This two-part paper describes a new approach to determine the effect of surface waviness, arising from manufacture of composite fan blades, on transition onset location movement and hence fan profile losses. The approach includes analysis and computations of unsteady disturbances in boundary layers over a wavy surface, assessed and supported by wind tunnel measurements of these disturbances and the transition location. An integrated framework is developed for analysis of surface waviness effects on natural transition. The framework, referred to as the extended eN method, traces the evolution of disturbance energy transfer in flow over a wavy surface, from external acoustic noise through exponential growth of Tollmien–Schlichting (TS) waves, to the start and end of the transition process. The computational results show that surface waviness affects the transition onset location due to the interaction between the surface waviness and the TS boundary layer instability and that the interaction is strongest when the geometric and TS wavelengths match. The condition at which this occurs, and the initial amplitude of the boundary layer disturbances that grow to create the transition onset is maximized, is called receptivity amplification. The results provide first-of-a-kind descriptions of the mechanism for the changes in transition onset location as well as quantitative calculations for the effects of surface waviness on fan performance due to changes in surface wavelength, surface wave amplitude, and the location at which the waviness is initiated on the fan blade.
New telechelic polymers and sequential copolymers by polyfunctional initiator‐transfer agents (inifers). XXX. Synthesis and quantitative terminal functionalization of α,ω‐diarylpolyisobutylenes (1983)

Abstract Novel aromatic‐telechelic polyisobutylenes were prepared and characterized: α,ω‐diphenylpolyisobutylene, α‐phenyl‐ω‐tolylpolyisobutylene, and α,ωditolylpolyisobutylene. The syntheses involved the preparation of asymmetric telechelic prepolymers (α‐phenyl‐ω‐tert‐chloropolyisobutylene and α‐tolyl‐ω‐tert‐chloropolyisobutylene) by the minifer method and quantitative alkylation of benzene and toluene by the prepolymer. The terminal aromatic rings of these telechelic polyisobutylenes were quantitatively nitrated, acetylated, and chlorosulfonated and a series of further novel telechelic products was obtained. Characterization of these derivatives provided additional proof for the telechelic structure of the starting prepolymers. The quantitative reduction of nitroaryl‐telechelic polyisobutylene by SnCl 2 /HCl led to aminoaryl‐telechelic polyisobutylene which was used to cure bisphenol‐A diglycidyl ether. These new flexible epoxy networks exhibited outstanding heat and hydrolytic stability combined with satisfactory mechanical properties.
Effets physiques et biologiques des faisceaux de protons balayés : mesures et modélisation pour des balayages séquentiels à haut débit (2016)

The main objective of this thesis is to develop and optimize algorithms for intensity modulated proton therapy, taking into account the physical and biological pencil beam properties. A model based on the summation and fluence weighted division of the pencil beams has been used. A new parameterization of the lateral dose distribution has been developed using a combination of three Gaussian functions. The algorithms have been implemented into a treatment planning system, then experimentally validated and compared with Monte Carlo simulations. Some approximations have been made and validated in order to achieve reasonable calculation times for clinical purposes. In a second phase, a collaboration with Institut Curie radiobiological teams has been started in order to implement radiobiological parameters and results into the optimization loop of the treatment planning process. Indeed, scanned pencil beams are pulsed and delivered at high dose rates (from 10 to 100 Gy/s), and the relative biological efficiency of protons is still relatively unknown given the wide diversity of use of these beams: the different models available and their dependence with linear energy transfers have been studied. A good agreement between dose calculations and measurements (deviations lower than 3 % and 2 mm) has been obtained. An experimental protocol has been set in order to qualify pulsed high dose rate effects and preliminary results obtained on one cell line suggested variations of the biological efficiency up to 10 %, though with large uncertainties.
Imaging through turbulence using compressive coherence sensing (2010)

Previous studies have shown that the isoplanatic distortion due to turbulence and the image of a remote object may be jointly estimated from the 4D mutual intensity across an aperture. This Letter shows that decompressive inference on a 2D slice of the 4D mutual intensity, as measured by a rotational shear interferometer, is sufficient for estimation of sparse objects imaged through turbulence. The 2D slice is processed using an iterative algorithm that alternates between estimating the sparse objects and estimating the turbulence-induced phase screen. This approach may enable new systems that infer object properties through turbulence without exhaustive sampling of coherence functions.