Structural Origins of Chiral Second-Order Optical Nonlinearity in Collagen: Amide I Band

AbstractThe molecular basis of nonlinear optical (NLO) chiral effects in the amide I region of type I collagen was investigated using sum-frequency generation vibrational spectroscopy; chiral and achiral tensor elements were separated using different input/output beam polarization conditions. Spectra were obtained from native rat tail tendon (RTT) collagen and from cholesteric liquid crystal-like (LC) type I collagen films. Although RTT and LC collagen both possess long-range order, LC collagen lacks the complex hierarchical organization of RTT collagen. Their spectra were compared to assess the role of such organization in NLO chirality. No significant differences were observed between RTT and LC with respect to chiral or achiral spectra. These findings suggest that amide I NLO chiral effects in type I collagen assemblies arise predominantly from the chiral organization of amide chromophores within individual collagen molecules, rather than from supramolecular structures. The study suggests that sum-frequency generation vibrational spectroscopy may be uniquely valuable in exploring fundamental aspects of chiral nonlinearity in complex macromolecular structures

GRAMMATICAL STRUCTURE OF PROVERBS AND SAYINGS AS A FORM OF REPRESENTATION OF LINGUISTIC AND CULTURAL INFORMATION

статье представлен результат работы по анализу морфологического состава устойчивых единиц, составляющих «Словарь русских пословиц и поговорок» В.П. Жукова. Пословицы и поговорки с компонентами – именами существительными сгруппированы в соответствии с грамматической формой падежа и выраженным конкретным значением с целью представления лингвострановедческого материала на грамматическом фоне.=The article presents the result of work on the analysis of the morphological composition of stable units that make up the «Dictionary of Russian Proverbs and Sayings» by V.P. Zhukov. Proverbs and sayings with components-nouns are grouped in accordance with the grammatical form of the case and expressed specific meaning in order to present linguistic and cultural material on the grammatical background

GRAMMATICAL STRUCTURE OF PROVERBS AND SAYINGS AS A FORM OF REPRESENTATION OF LINGUISTIC AND CULTURAL INFORMATION

статье представлен результат работы по анализу морфологического состава устойчивых единиц, составляющих «Словарь русских пословиц и поговорок» В.П. Жукова. Пословицы и поговорки с компонентами – именами существительными сгруппированы в соответствии с грамматической формой падежа и выраженным конкретным значением с целью представления лингвострановедческого материала на грамматическом фоне.=The article presents the result of work on the analysis of the morphological composition of stable units that make up the «Dictionary of Russian Proverbs and Sayings» by V.P. Zhukov. Proverbs and sayings with components-nouns are grouped in accordance with the grammatical form of the case and expressed specific meaning in order to present linguistic and cultural material on the grammatical background

Neurology

Contains reports on eight research projects.U.S. Navy (Office of Naval Research (Nonr-1841(70))U. S. Public Health Service (MH-06175-02)U. S. Air Force (AF49(638)-1313)U. S. Public Health Service (B-3055-4)U. S. Public Health Service (B-3090-4

Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies

Abstract Background Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133– and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens

Oncolytic DNX-2401 Virotherapy Plus Pembrolizumab in Recurrent Glioblastoma: A Phase 1/2 Trial

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients

Euclid: The importance of galaxy clustering and weak lensing cross-correlations within the photometric Euclid survey

Context. The data from the Euclid mission will enable the measurement of the angular positions and weak lensing shapes of over a billion galaxies, with their photometric redshifts obtained together with ground-based observations. This large dataset, with well-controlled systematic effects, will allow for cosmological analyses using the angular clustering of galaxies (GCph) and cosmic shear (WL). For Euclid, these two cosmological probes will not be independent because they will probe the same volume of the Universe. The cross-correlation (XC) between these probes can tighten constraints and is therefore important to quantify their impact for Euclid. Aims. In this study, we therefore extend the recently published Euclid forecasts by carefully quantifying the impact of XC not only on the final parameter constraints for different cosmological models, but also on the nuisance parameters. In particular, we aim to decipher the amount of additional information that XC can provide for parameters encoding systematic effects, such as galaxy bias, intrinsic alignments (IAs), and knowledge of the redshift distributions. Methods. We follow the Fisher matrix formalism and make use of previously validated codes. We also investigate a different galaxy bias model, which was obtained from the Flagship simulation, and additional photometric-redshift uncertainties; we also elucidate the impact of including the XC terms on constraining these latter. Results. Starting with a baseline model, we show that the XC terms reduce the uncertainties on galaxy bias by ∼17% and the uncertainties on IA by a factor of about four. The XC terms also help in constraining the γ parameter for minimal modified gravity models. Concerning galaxy bias, we observe that the role of the XC terms on the final parameter constraints is qualitatively the same irrespective of the specific galaxy-bias model used. For IA, we show that the XC terms can help in distinguishing between different models, and that if IA terms are neglected then this can lead to significant biases on the cosmological parameters. Finally, we show that the XC terms can lead to a better determination of the mean of the photometric galaxy distributions. Conclusions. We find that the XC between GCph and WL within the Euclid survey is necessary to extract the full information content from the data in future analyses. These terms help in better constraining the cosmological model, and also lead to a better understanding of the systematic effects that contaminate these probes. Furthermore, we find that XC significantly helps in constraining the mean of the photometric-redshift distributions, but, at the same time, it requires more precise knowledge of this mean with respect to single probes in order not to degrade the final “figure of merit”

Euclid: Forecasts for k-cut 3×2 Point Statistics

Modelling uncertainties at small scales, i.e. high k in the power spectrum P(k), due to baryonic feedback, nonlinear structure growth and the fact that galaxies are biased tracers poses a significant obstacle to fully leverage the constraining power of the Euclid wide-field survey. k-cut cosmic shear has recently been proposed as a method to optimally remove sensitivity to these scales while preserving usable information. In this paper we generalise the k-cut cosmic shear formalism to 3×2 point statistics and estimate the loss of information for different k-cuts in a 3×2 point analysis of the Euclid data. Extending the Fisher matrix analysis of Euclid Collaboration: Blanchard et al. (2019), we assess the degradation in constraining power for different k-cuts. We find that taking a k-cut at 2.6 h Mpc⁻¹ yields a dark energy Figure of Merit (FOM) of 1018. This is comparable to taking a weak lensing cut at ℓ=5000 and a galaxy clustering and galaxy-galaxy lensing cut at ℓ=3000 in a traditional 3×2 point analysis. We also find that the fraction of the observed galaxies used in the photometric clustering part of the analysis is one of the main drivers of the FOM. Removing 50% (90%) of the clustering galaxies decreases the FOM by 19% (62%). Given that the FOM depends so heavily on the fraction of galaxies used in the clustering analysis, extensive efforts should be made to handle the real-world systematics present when extending the analysis beyond the luminous red galaxy (LRG) sample

Euclid: Forecasts from the void-lensing cross-correlation

The Euclid space telescope will survey a large dataset of cosmic voids traced by dense samples of galaxies. In this work we estimate its expected performance when exploiting angular photometric void clustering, galaxy weak lensing, and their cross-correlation. To this aim, we implemented a Fisher matrix approach tailored for voids from the Euclid photometric dataset and we present the first forecasts on cosmological parameters that include the void-lensing correlation. We examined two different probe settings, pessimistic and optimistic, both for void clustering and galaxy lensing. We carried out forecast analyses in four model cosmologies, accounting for a varying total neutrino mass, Mν, and a dynamical dark energy (DE) equation of state, w(z), described by the popular Chevallier-Polarski-Linder parametrization. We find that void clustering constraints on h and Ωb are competitive with galaxy lensing alone, while errors on ns decrease thanks to the orthogonality of the two probes in the 2D-projected parameter space. We also note that, as a whole, with respect to assuming the two probes as independent, the inclusion of the void-lensing cross-correlation signal improves parameter constraints by 10 − 15%, and enhances the joint void clustering and galaxy lensing figure of merit (FoM) by 10% and 25%, in the pessimistic and optimistic scenarios, respectively. Finally, when further combining with the spectroscopic galaxy clustering, assumed as an independent probe, we find that, in the most competitive case, the FoM increases by a factor of 4 with respect to the combination of weak lensing and spectroscopic galaxy clustering taken as independent probes. The forecasts presented in this work show that photometric void clustering and its cross-correlation with galaxy lensing deserve to be exploited in the data analysis of the Euclid galaxy survey and promise to improve its constraining power, especially on h, Ωb, the neutrino mass, and the DE evolution