Miracle-dz/UniFAR-FTUs huggingface dataset:
The Immunocytokine FAP-IL-2v Enhances Anti-Neuroblastoma Efficacy of the Anti-GD2 Antibody Dinutuximab Beta

Simple Summary Since IL-2 co-treatment did not show any therapeutic benefit in the GD2-directed treatment of high-risk neuroblastoma (NB) but strongly induced regulatory T cells (Treg), we investigated here the immunocytokine FAP-IL-2v stimulating NK and cytotoxic T cells without induction of Treg. We first detected FAP on NB- and myeloid-derived suppressor cells (MDCS) in tumor tissue and showed a tumor-cell-dependent enhancement in FAP expression by fibroblasts. Treatment of leukocytes with FAP-IL-2v increased ADCC mediated by the anti-GD2 antibody dinutuximab beta (DB) against NB cells. We next evaluated the antitumor efficacy of a combinatorial immunotherapy by applying DB and FAP-IL-2v and observed strongly reduced tumor growth and improved survival in experimental mice. Analysis of tumor tissue revealed increased NK and cytotoxic T cell numbers and reduced Treg compared to controls. Our data show that FAP-IL-2v is a potent immunocytokine that augments the efficacy of DB against NB, providing a promising alternative to IL-2. Abstract Treatment of high-risk neuroblastoma (NB) patients with the anti-GD2 antibody (Ab) dinutuximab beta (DB) improves survival by 15%. Ab-dependent cellular cytotoxicity (ADCC) is the major mechanism of action and is primarily mediated by NK cells. Since IL-2 co-treatment did not show a therapeutic benefit but strongly induced Treg, we investigated here a DB-based immunotherapy combined with the immunocytokine FAP-IL-2v, which comprises a fibroblast activation protein α (FAP)-specific Ab linked to a mutated IL-2 variant (IL-2v) with abolished binding to the high-affinity IL-2 receptor, thus stimulating NK cells without induction of Treg. Effects of FAP-IL-2v on NK cells, Treg and ADCC mediated by DB, as well as FAP expression in NB, were investigated by flow cytometry, calcein-AM-based cytotoxicity assay and RT-PCR analysis. Moreover, the impact of soluble factors released from tumor cells on FAP expression by primary fibroblasts was assessed. Finally, a combined immunotherapy with DB and FAP-IL-2v was evaluated using a resistant syngeneic murine NB model. Incubation of leukocytes with FAP-IL-2v enhanced DB-specific ADCC without induction of Treg. FAP expression on NB cells and myeloid-derived suppressor cells (MDCS) in tumor tissue was identified. A tumor-cell-dependent enhancement in FAP expression by primary fibroblasts was demonstrated. Combination with DB and FAP-IL-2v resulted in reduced tumor growth and improved survival. Analysis of tumor tissue revealed increased NK and cytotoxic T cell numbers and reduced Treg compared to controls. Our data show that FAP-IL-2v is a potent immunocytokine that augments the efficacy of DB against NB, providing a promising alternative to IL-2.
New evidence for dark matter

We present a new universal relation, satisfied by matter distributions at all observed scales, and show its amazingly good and detailed agreement with the predictions of the most up-to-date pure dark matter simulations of structure formation in the Universe. This work extends the previous analysis [0904.4054; 0909.5203] to a larger range of masses, demonstrates a different scaling law, and compares it with numerical simulations. This behaviour seems to be insensitive to the complicated feedback of baryons on dark matter. Therefore, it potentially allows to compare theoretical predictions directly with observations, thus providing a new tool to constrain the properties of dark matter. Such a universal property, observed in structures of all sizes (from dwarf spheroidal galaxies to galaxy clusters), is difficult to explain without dark matter, thus providing new evidence for its existence.
Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Combination Therapy as First-Line Treatment for Patients with Advanced EGFR-Mutated, Non-Small Cell Lung Cancer: A Systematic Review and Bayesian Network Meta-Analysis

Simple Summary As clinical practice lacks direct data for head-to-head comparisons across targeted combination approaches, we performed a Bayesian network meta-analysis to indirectly analyze the efficacy and safety of various combination therapies. A total of 12 modes of combination TKI therapy are compared. We find that radiation combined with EGFR-Tyrosine Kinase Inhibitor (TKI), is superior to other combination treatments in progression free survival (PFS) and overall survival (OS). TKI combined with chemotherapy may improve objective response rate (ORR), PFS, and OS, but may increase grade 3 or higher hematological side events. Combining efficacy and safety, we show that macro-monoclonal antibody antiangiogenic drugs, such as bevacizumab or ramucirumab, may be the ideal combination treatment choice, while the efficacy of small molecule inhibitors, such as apatinib, needs more investigation. Our findings have significant implications for the clinical management of non-small cell lung cancer patients, providing new ideas and evidence for doctors’ decision making, as well as pointing to future research options. Abstract (1) Background: Several randomized controlled trials (RCTs) have been conducted in combination with Efficacy and Safety of Epidermal Growth Factor Receptor(EGFR)-Tyrosine Kinase Inhibitor (TKI) for the first-line treatment of patients with advanced non-small cell lung cancer; however, head-to-head comparisons of combination therapies are still lacking. Therefore, this study aims to compare the efficacy and safety of various combination treatments. (2) Methods: We conducted a systematic review and Bayesian network meta-analysis by searching MEDLINE, EMBASE, and COCHRANE for relevant RCTs. (3) Results: TKI combined with antiangiogenic therapy, chemotherapy, or radiation achieved a significant benefit compared with TKI alone for progression free survival (PFS). A combination with radiation yielded better benefits in PFS than any other treatment. In terms of overall survival (OS), only the combination with pemetrexed and carboplatin (HR = 0.63, 95% credible interval 0.43–0.86)/radiation (0.44, 0.23–0.83) was superior to TKI alone. All of the combination therapies may increase the incidence of ≥Grade 3 AEs, as the pooled RRs are over 1; different toxicity spectrums were revealed for individual treatments. (4) Conclusions: The TKI combination of radiation/pemetrexed and carboplatin could provide the best antitumor effects among the first generation TKI-based treatments. Considering safety, ramucirumab and bevacizumab may be the ideal additions to TKIs (systematic review registration: PROSPERO CRD42022350474).
An infrared study of local galaxy mergers

We combine a large, homogeneous sample of $\sim$3000 local mergers with the Imperial IRAS Faint Source Redshift Catalogue (IIFSCz), to perform a blind far-infrared (FIR) study of the local merger population. The IRAS-detected mergers are mostly ($98\%$) spiral-spiral systems, residing in low density environments, a median FIR luminosity of $10^{11} L_\odot$ (which translates to a median star formation rate of around 15$M_\odot yr^{-1}$). The FIR luminosity -- and therefore the star formation rate -- shows little correlation with group richness and scales with the total stellar mass of the system, with little or no dependence on the merger mass ratio. In particular, minor mergers (mass ratios $<1:3$) are capable of driving strong star formation (between 10 and $173 M_\odot yr^{-1}$) and producing systems that are classified as LIRGs, luminous infrared galaxies ($65\%$ of our LIRGs are minor mergers), with some minor-merging systems being close to the ultra luminous infrared galaxy (ULIRG) limit. Optical emission line ratios indicate that the AGN fraction increases with increasing FIR luminosity, with all ULIRG mergers having some form of AGN activity. Finally, we estimate that the LIRG-to-ULIRG transition along a merger sequence typically takes place over a relatively short timescale of $\sim$160 Myr.
Selective growth of epitaxial Sr2IrO4 by controlling plume dimensions in pulsed laser deposition

We report that epitaxial Sr2IrO4 thin-films can be selectively grown using pulsed laser deposition (PLD). Due to the competition between the Ruddlesden-Popper phases of strontium iridates (Srn+1IrnO3n+1), conventional PLD methods often result in mixed phases of Sr2IrO4 (n = 1), Sr3Ir2O7 (n = 2), and SrIrO3 (n = ∞). We have discovered that reduced PLD plume dimensions and slow deposition rates are the key for stabilizing pure Sr2IrO4 phase thin-films, identified by real-time in-situ monitoring of their optical spectra. The slow film deposition results in a thermodynamically stable TiO2\\SrO\IrO2\SrO\SrO configuration at an interface rather than TiO2\\SrO\SrO\IrO2\SrO between a TiO2-terminated SrTiO3 substrate and a Sr2IrO4 thin film, which is consistent with other layered oxides grown by molecular beam epitaxy. Our approach provides an effective method for using PLD to achieve pure phase thin-films of layered materials that are susceptible to several energetically competing phases.
Electroweak Effective Operators and Higgs Physics

We derive bounds from oblique parameters on the dimension-6 operators of an effective field theory of electroweak gauge bosons and the Higgs doublet. The loop-induced contributions to the ΔS, ΔT, and ΔU oblique parameters are sensitive to these contributions, and we pay particular attention to the role of renormalization when computing loop corrections in the effective theory. Limits on the coefficients of the effective theory from loop contributions to oblique parameters yield complementary information to direct Higgs production measurements. © 2014 American Physical Society.
Quasinormal modes of the BTZ black hole are generated by surface waves supported by its boundary at infinity

We develop the complex angular momentum method in the context of the BTZ black hole physics. This is achieved by extending a formalism introduced a long time ago by Arnold Sommerfeld, which allows us to define and use the concept of the Regge pole in a framework where the notion of an S matrix does not exist. The Regge poles of the BTZ black hole are exactly obtained, and from the associated Regge trajectories we determine its quasinormal mode complex frequencies. Furthermore, our approach permits us to physically interpret them: they appear as Breit-Wigner-type resonances generated by surface waves supported by the black hole boundary at infinity which acts as a photon sphere.
IMPLEMENTING TURBULENCE TRANSPORT IN THE CRONOS FRAMEWORK AND APPLICATION TO THE PROPAGATION OF CMEs

We present the implementation of turbulence transport equations in addition to the Reynolds-averaged magnetohydrodynamic equations within the Cronos framework. The model is validated by comparisons with earlier findings before it is extended to be applicable to regions in the solar wind that are not highly super-Alfvénic. We find that the respective additional terms result in absolute normalized cross-helicity to decline more slowly, while a proper implementation of the mixing terms can even lead to increased cross-helicities in the inner heliosphere. The model extension allows us to place the inner boundary of the simulations closer to the Sun, where we choose its location at 0.1 AU for future application to the Wang–Sheeley–Arge model. Here, we concentrate on effects on the turbulence evolution for transient events by injecting a coronal mass ejection (CME). We find that the steep gradients and shocks associated with these structures result in enhanced turbulence levels and reduced cross-helicity. Our results can now be used straightforwardly for studying the transport of charged energetic particles, where the elements of the diffusion tensor can now benefit from the self-consistently computed solar wind turbulence. Furthermore, we find that there is no strong back-reaction of the turbulence on the large-scale flow so that CME studies concentrating on the latter need not be extended to include turbulence transport effects.
Detection of interactions via generalized factorial cumulants in systems in and out of equilibrium

We introduce time-dependent, generalized factorial cumulants $C_s^m(t)$ of the full counting statistics of electron transfer as a tool to detect interactions in nanostructures. The violation of the sign criterion $(-1)^{m-1} C^m_s(t)\ge0$ for \emph{any} time $t$, order $m$, and parameter $s$ proves the presence of interactions. For given system parameters, there is a minimal time span $t_\text{min}$ and a minimal order $m$ to observe the violation of the sign criterion. We demonstrate that generalized factorial cumulants are more sensitive to interactions than ordinary ones and can detect interactions even in regimes where ordinary factorial cumulants fail. We illustrate our findings with the example of a quantum dot tunnel coupled to electronic reservoirs either in or out of equilibrium.
Assessing Colour-dependent Occupation Statistics Inferred from Galaxy Group Catalogues

We investigate the ability of current implementations of galaxy group finders to recover colour-dependent halo occupation statistics. To test the fidelity of group catalogue inferred statistics, we run three different group finders used in the literature over a mock that includes galaxy colours in a realistic manner. Overall, the resulting mock group catalogues are remarkably similar, and most colour-dependent statistics are recovered with reasonable accuracy. However, it is also clear that certain systematic errors arise as a consequence of correlated errors in group membership determination, central/satellite designation, and halo mass assignment. We introduce a new statistic, the halo transition probability (HTP), which captures the combined impact of all these errors. As a rule of thumb, errors tend to equalize the properties of distinct galaxy populations (i.e. red versus blue galaxies or centrals versus satellites), and to result in inferred occupation statistics that are more accurate for red galaxies than for blue galaxies. A statistic that is particularly poorly recovered from the group catalogues is the red fraction of central galaxies as a function of halo mass. Group finders do a good job in recovering galactic conformity, but also have a tendency to introduce weak conformity when none is present. We conclude that proper inference of colour-dependent statistics from group catalogues is best achieved using forward modelling (i.e. running group finders over mock data) or by implementing a correction scheme based on the HTP, as long as the latter is not too strongly model dependent.
SCATTER-FREE PICKUP IONS BEYOND THE HELIOPAUSE AS A MODEL FOR THE INTERSTELLAR BOUNDARY EXPLORER RIBBON

We present a new kinetic-gasdynamic model of the solar wind interaction with the local interstellar medium. The model incorporates several processes suggested earlier for the origin of the ribbon—the most prominent feature seen in the all-sky maps of heliospheric energetic neutral atoms (ENAs) discovered by the Interstellar Boundary Explorer (IBEX). The ribbon is a region of enhanced fluxes of ENAs crossing almost the entire sky. Soon after the ribbon's discovery, it was realized that the enhancement of the fluxes could be in the directions where the radial component of the interstellar magnetic field around the heliopause is close to zero. Our model includes secondary charge exchange of the interstellar H atoms with the interstellar pickup protons outside the heliopause. Previously, in the frame of a kinetic-gasdynamic model where pickup protons are treated as a separate kinetic component, it was shown that the interstellar pickup protons outside the heliopause may be a significant source of ENAs at energies above 1 keV. The key difference between the current work and the previous models is in the assumption of no pitch-angle scattering for newly created pickup protons outside the heliopause. We demonstrate that in the limit of no pitch-angle scattering ribbon of enhanced ENA fluxes appears in the model, and this may qualitatively explain the ribbon discovered by IBEX.
THE MOLECULAR GAS CONTENT OF z = 3 LYMAN BREAK GALAXIES: EVIDENCE OF A NON-EVOLVING GAS FRACTION IN MAIN-SEQUENCE GALAXIES AT z > 2

We present observations of the CO[J = 3 → 2] emission toward two massive and infrared luminous Lyman break galaxies (LBGs) at z = 3.21 and z = 2.92, using the IRAM Plateau de Bure Interferometer, placing first constraints on the molecular gas masses (Mgas) of non-lensed LBGs. Their overall properties are consistent with those of typical (main-sequence) galaxies at their redshifts, with specific star formation rates ∼1.6 and ∼2.2 Gyr−1, despite their large infrared luminosities (LIR ≈ (2–3) × 1012 L☉) derived from Herschel. With one plausible CO detection (spurious detection probability of 10−3) and one upper limit, we investigate the evolution of the molecular gas-to-stellar mass ratio (Mgas/M*) with redshift. Our data suggest that the steep evolution of Mgas/M* of normal galaxies up to z ∼ 2 is followed by a flattening at higher redshifts, providing supporting evidence for the existence of a plateau in the evolution of the specific star formation rate at z > 2.5.
Demographic consequences of changes in environmental periodicity.

The fate of natural populations is mediated by complex interactions among vital rates, which can vary within and among years. While the effects of random, among-year variation in vital rates have been studied extensively, relatively little is known about how periodic, non-random variation in vital rates affects populations. This knowledge gap is potentially alarming as global environmental change is projected to alter common periodic variations, such as seasonality. We investigated the effects of changes in vital-rate periodicity on populations of three species representing different forms of adaptation to periodic environments: the yellow-bellied marmot (Marmota flaviventer), adapted to strong seasonality in snowfall; the meerkat (Suricata suricatta), adapted to inter-annual stochasticity as well as seasonal patterns in rainfall; and the dewy pine (Drosophyllum lusitanicum), adapted to fire regimes and periodic post-fire habitat succession. To assess how changes in periodicity affect population growth, we parameterized periodic matrix population models and projected population dynamics under different scenarios of perturbations in the strength of vital-rate periodicity. We assessed the effects of such perturbations on various metrics describing population dynamics, including the stochastic growth rate, log λS . Overall, perturbing the strength of periodicity had strong effects on population dynamics in all three study species. For the marmots, log λS decreased with increased seasonal differences in adult survival. For the meerkats, density dependence buffered the effects of perturbations of periodicity on log λS . Finally, dewy pines were negatively affected by changes in natural post-fire succession under stochastic or periodic fire regimes with fires occurring every 30 years, but were buffered by density dependence from such changes under presumed more frequent fires or large-scale disturbances. We show that changes in the strength of vital-rate periodicity can have diverse but strong effects on population dynamics across different life histories. Populations buffered from inter-annual vital-rate variation can be affected substantially by changes in environmentally-driven vital-rate periodic patterns; however, the effects of such changes can be masked in analyses focusing on inter-annual variation. As most ecosystems are affected by periodic variations in the environment such as seasonality, assessing their contributions to population viability for future global-change research is crucial.
Iterative Learning Control: Robustness and Monotonic Convergence for Interval Systems

This monograph studies the design of robust, monotonically-convergent iterative learning controllers for discrete-time systems. Two key problems with the fundamentals of iterative learning control (ILC) design as treated by existing work are: first, many ILC design strategies assume nominal knowledge of the system to be controlled and; second, it is well-known that many ILC algorithms do not produce monotonic convergence, though in applications monotonic convergence is often essential. Iterative Learning Control takes account of the recently-developed comprehensive approach to robust ILC analysis and design established to handle the situation where the plant model is uncertain. Considering ILC in the iteration domain, it presents a unified analysis and design framework that enables designers to consider both robustness and monotonic convergence for typical uncertainty models, including parametric interval uncertainties, iteration-domain frequency uncertainty, and iteration-domain stochastic uncertainty. Topics include: Use of a lifting technique to convert the two-dimensional ILC system, which has dynamics in both the time and iteration domains, into the supervector framework, which yields a one-dimensional system, with dynamics only in the iteration domain. Development of iteration-domain uncertainty models in the supervector framework. ILC design for monotonic convergence when the plant is subject to parametric interval uncertainty in its Markov matrix. An algebraic H-infinity design methodology for ILC design when the plant is subject to iteration-domain frequency uncertainty. Development of Kalman-filter-based ILC algorithms when the plant is subject to iteration-domain stochastic uncertainties. Analytical determination of the base-line error of ILC algorithms. Solutions to three fundamental robust interval computational problems (used as basic tools for designing robust ILC controllers): finding the maximum singular value of an interval matrix, determining the robust stability of interval polynomial matrix, and obtaining the power of an interval matrix. Iterative Learning Control will be of great interest to academic researchers in control theory and to industrial control engineers working in robotics-oriented manufacturing and batch-processing-based industries. Graduate students of intelligent control will also find this volume instructive.
EFFECT OF HUMIC ACID AND ALGAE EXTRACT ON PRODUCTIVITY OF RUTA GRAVEOLENS L. PLANT UNDER SINAI CONDITIONS

his study was conducted during the two successive seasons of 2019-2020 and 2020-2021 at Ras Sudr Station farm in South Sinai Governorate, Egypt, to study the importance of using humic acid and spraying with algae extract to reduce water loss from the soil and reduce the effect of irrigation with saline water on the growth of Ruta graveolens plants under North Sinai conditions. Results showed a significant increase in the studied parameters when treated with different rates of humic acid alone and different concentrations of algae extract alone. Also, the interaction treatment between humic acid and algae extract at 4 kg/feddan and 4 cm/liter, respectively, gave the highest values in all characteristics such as vegetative growth, oil production, active ingredients, and chemical composition. On the other hand, the analysis of the components of the volatile oil of Ruta graveolens gave the presence of three main compounds of the oil components; 2-undecan is the main compound, followed by 2-nonan, then 2-methyl-undecanal. and spraying with boron on growth, the yield of fruits, and volatile oil per plant and per feddan. Results indicated significant differences that led to an increase in growth characteristics and yield productivity with the treatment of humic acid and biofertilizer, which recorded the best values in the two studied seasons, as well as the highest percentages of essential oil components such as linalool, geraniol and limonene. The study aims to investigate the effect of using humic acid and spraying with algae extract to reduce water loss from the soil and reduce the harmful effects of irrigation water salinity on the growth of R. graveolens plants under North Sinai conditions.