Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative, Spatially Defined Expression of Leukocyte-associated Immunoglobulin-like Receptor in Non–small Cell Lung Cancer

Targeting the interaction of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) and its ligands has been shown to reinstate antitumor immunity. In addition, the introduction of the LAIR-1 decoy protein, LAIR-2, sensitizes previously resistant lung tumors to programmed death-1 (PD-1) blockade, indicating the potential of LAIR-1 as an alternative marker for anti-PD-1 resistance in lung cancer. Here, we assessed LAIR-1 as compared with programmed death-ligand 1 (PD-L1) expression in various tumors, with a focus on non–small cell lung cancer (NSCLC) and its histologic subtypes using multiplexed quantitative immunofluorescence (mQIF) in 287 (discovery cohort) and 144 (validation cohort) patients with NSCLC. In addition, using multispectral imaging technology on mQIF images, we evaluated the localization of LAIR-1 on various cell types. We observed that CD14+, CD68+, and CD163+ monocytes and CK+ tumor cells predominantly expressed LAIR-1 more than other cell types. Furthermore, LAIR-1 expression in the tumor compartment was significantly higher in patients with lung adenocarcinoma (LUAD) than those with lung squamous cell carcinoma subtype (**, P = 0.003). Our results indicated that high tumor LAIR-1 expression in patients with LUAD is negatively associated with OS (overall survival, HR = 2.4; *, P = 0.02) highlighting its prognostic value in LUAD but not in other subtypes. The Pearson correlation between LAIR-1 and PD-L1 is 0.31; however, mutual exclusive staining pattern (i.e., several cases were positive for LAIR-1 and negative for PD-L1) was observed. Altogether, our data suggest that the combination therapy of anti-PD-1/PD-L1 with anti-LAIR-1 or the anti-LAIR-1 monotherapy alone may be promising cancer immunotherapeutic strategies. Significance: The spatial, quantitative assessment of LAIR-1 in NSCLC shows positive association of OS with high LAIR-1+/CD68+ cell densities and negative association of OS with high LAIR-1 expression in LUAD tumor subtype.
Gradient regularity via rearrangements for $p$-Laplacian type elliptic boundary value problems

A sharp estimate for the decreasing rearrangement of the length of the gradient of solutions to a class of nonlinear Dirichlet and Neumann elliptic boundary value problems is established under weak regularity assumptions on the domain. As a consequence, the problem of gradient bounds in norms depending on global integrability properties is reduced to one-dimensional Hardy-type inequalities. Applications to gradient estimates in Lebesgue, Lorentz, Zygmund, and Orlicz spaces are presented.
A DNS of a Turbulent Flow in a Rough-Wall Channel Using Roughness Elements Model

A Direct Numerical Simulation (DNS) is conducted for a turbulent flow in a channel bounded by one rough and another smooth wall. Rough wall is modeled by roughness elements represented by zero-volume wall-normal lines extending from the wall surface to around 15-30 in wall unit, which generate Stokes drag to the local flow. Global Reynolds number based on the mean friction velocities on two walls and channel half width is 400. It is inteded here to demonstrate the validity of the roughness model, comparing the obtained flow with available experimental results. It was confirmed that the model reproduces the experimentally obtained mean flow satisfactorily and that turbulence modification by roughness in the layer above the top of roughness elements is qualitatively coincident with the experimental results.
An experimental study of the decay of temperature fluctuations in grid-generated turbulence

Previous measurements of the decay rate of the fluctuation intensity of passive scalars in grid-generated turbulence show large variation. New results presented here show that the decay rate of passive temperature fluctuations produced by heating the grid is a function of the initial temperature fluctuation intensity. Although a full reason for this is wanting, spectra of the temperature fluctuations show that, by varying the heat applied to the grid, the wavenumber of the maximum in the temperature spectrum changes, indicating that the geometry of the thermal fluctuations is being altered in some way. In these experiments the one-dimensional temperature spectrum shows an anomalous $-\frac{5}{3}$ slope. In order to eliminate the dependence of the decay rate of the temperature fluctuations on their intensity, we describe a new way of generating temperature fluctuations by means of placing a heated parallel array of fine wires (a mandoline) downstream from the unheated grid. Results of this experiment show that the decay rate of passive thermal fluctuations is uniquely determined by the wave-number of the initial temperature fluctuations. In this type of flow there appears to be no equilibrium value for the thermal fluctuation decay rate and hence for the mechanical/thermal time-scale ratio since the thermal fluctuation decay rate does not change within the tunnel length, which is the equivalent of nearly one turbulence decay time.
XMM-Newton Observations Reveal the X-Ray Counterpart of the Very High Energy Gamma-Ray Source HESS J1640–465

We present X-ray observations of the as of yet unidentified very high energy (VHE) γ-ray source HESS J1640-465 with the aim of establishing a counterpart of this source in the keV energy range, and identifying the mechanism responsible for the VHE emission. The 21.8 ks XMM-Newton observation of HESS J1640-465 in 2005 September represents a significant improvement in sensitivity and angular resolution over previous ASCA studies in this region. These new data show a hard-spectrum X-ray-emitting object at the centroid of the H.E. S.S. source, within the shell of the radio supernova remnant (SNR) G338.3-0.0. This object is consistent with the position and flux previously measured by both ASCA and Swift XRT, but is now shown to be significantly extended. We argue that this object is very likely the counterpart to HESS J1640-465, and that both objects may represent the pulsar wind nebula of an as of yet undiscovered pulsar associated with G338.3-0.0.
On improved predictive density estimation with parametric constraints

We consider the problem of predictive density estimation for normal models under Kullback-Leibler loss (KL loss) when the parameter space is constrained to a convex set. More particularly, we assume that X ∼ Np(µ,vxI) is observed and that we wish to estimate the density of Y ∼ Np(µ,vyI) under KL loss when µ is restricted to the convex set C ⊂ R p . We show that the best unrestricted invariant predictive density estimator ˆ pU is dominated by the Bayes estimator ˆ pπC associ
A Comprehensive Evaluation of GRACE‐Like Terrestrial Water Storage (TWS) Reconstruction Products at an Interannual Scale During 1981–2019

Given the success of the Gravity Recovery and Climate Experiment (GRACE) mission in mapping terrestrial water storage (TWS) since 2002, recent reconstructions of long‐term TWS rely on the use of statistical machine learning to apply GRACE‐derived information to past decades. Evaluating the interannual accuracy during nonobservational periods is a key challenge. This study develops a comprehensive framework to discuss the interannual accuracy of three different TWS reconstructions during 1981–2019, including (a) global‐scale accuracy assessment using GRACE and satellite laser ranging data; (b) regional‐scale accuracy testing across various underlying surfaces (i.e., rivers, lakes, and glaciers); and (c) investigation of relevant evidence from other Earth subsystems (i.e., historic climate events, sea level budget, and polar motion). Among the three reconstructions, the one that additionally corrects glacial TWS changes (REC2) detects a breaking point in the 1990s and further closes the interannual sea level budget with an absolute difference reduction to 5.13 mm; the reconstruction that is forced by local meteorological conditions (REC1), accounting for 54% of the GRACE‐derived signal energy, underestimates glacial TWS variability but outperforms the other reconstructions in reproducing lake levels, basin‐scale water balances, and climate events at the interannual scale, while the others consider 95%–99% of the GRACE‐derived signal energy. The relatively high accuracy of REC1 (and REC2) in reflecting interannual changes in nonglacial (and glacial) regions is further confirmed by explaining the χ2‐ (and χ1‐) component polar motion. Ten to 20% of the interannual polar motion remains unexplained, indicating room for improvement in interannual TWS reconstruction.
Surface fluxes in the North Atlantic current during CATCH/FASTEX

CATCH (Couplage avec l'Atmosphère en Conditions Hivernales) was the oceanic component of FASTEX (Fronts and Atlantic Storm‐Track Experiment). It took place in January and February 1997, in the Newfoundland Basin near 47°N, 40°W, a region characterized by the presence of the warm North Atlantic Current and cold surrounding waters. CATCH was devoted to the study of the parametrization of surface turbulent fluxes in strong winds and changing directions, the surface‐flux variability related to the passage of atmospheric fronts and the influence on fluxes of the strong sea surface temperature gradients associated with the North Atlantic Current. This paper presents first results of ship data analysis. A large range of wind and stratification conditions were experienced: 5% of measured winds were higher than 20 m s‐1; 30% of unstable stratification (air‐sea temperature differences lower than −5 °C) and 30% of very dry conditions (air‐sea moisture differences lower than −2.5 g kg−1) were sampled. Surface turbulent heat and momentum fluxes were obtained using the inertial‐dissipative method from which a bulk algorithm was derived. A significant increase of latent‐heat and momentum‐transfer coefficients with increasing wind is obtained. This parametrization is compared to others published using the CATCH dataset. For high winds and unstable stratifications, differences between schemes reach 200 W m−2 for latent‐heat flux values of 600 W m−2. Radiative and turbulent ship‐measured fluxes are compared with modelled fluxes from the European Centre for Medium‐Range Forecasts (ECMWF) along the ship's trajectory: each component of the net heat budget is higher in the ECMWF model, consequently the heat loss of the ocean is 35% higher in the model. Finally, the effect of sea surface temperature fronts on surface turbulent fluxes is analysed by evaluating the contribution of the various terms in the flux variations, showing a significant impact of the surface temperature change in all unperturbed cases.
The Distribution of Zeros of an Irreducible Curve over a Finite Field

Abstract Let f ( x , y ) be a polynomial defined over Z in two variables of total degree d ⩾2, and let Vp ={( x , y )∈ C p : f ( x , y )≡0 (mod p )} for each prime p , where C p ={( x , y )∈ Z 2 : 0⩽ x p and 0⩽ y p }. In this paper, we show that if f ( x , y ) is absolutely irreducible modulo p for all sufficiently large p , then we have the following distribution formula for the zeros of f ( x , y ) modulo p ,[formula]where δ is any given real number with 0⩽ δ ⩽1, and[formula]Here ‖ θ ‖ denotes the nearest distance from θ to integer, and β is a real number with 0⩽ β ⩽ 1 2 .
When a Queue Looks the Same to an Arriving Customer as to an Observer

In a queue with a Poisson arrival distribution, the probability distribution state of the queue at any time is independent of whether or not an arrival occurs at that time. In particular, in a stationary queue with Poisson arrivals, the stationary distribution of the number of waiting customers in the queue at an arbitrary time is equal to the stationary distribution of the number of customers waiting in the queue when a new customer arrives.
A complete solution to the existence problem for 1‐rotational k‐cycle systems of Kv

The necessary and sufficient conditions for the existence of a 1‐rotational k‐cycle system of the complete graph Kv are established. The proof provides an algorithm able to determine, directly and explicitly, an odd k‐cycle system of Kv whenever such a system exists. © 2009 Wiley Periodicals, Inc. J Combin Designs 17: 283–293, 2009
Smoking Habits and Attitudes toward Smoking in Patients with Severe Mental Illness in Residential Facilities in Insular Greece

Smoking may contribute to increased cardiovascular morbidity and mortality in patients with schizophrenia spectrum disorders. The objective of the present study is to explore the attitudes toward smoking in patients with severe mental illness in residential rehabilitation facilities in insular Greece. The patients (n = 103) were studied with the use of a questionnaire based on a semi-structured interview. Most of the participants (68.3%) were current regular smokers, had been smoking for 29 years and started smoking at an early age. The majority (64.8%) reported having tried to quit smoking in the past, and only half had been advised by a physician to quit. The patients agreed on the rules for smoking and believed that the staff should avoid smoking in the facility. The years of smoking were statistically significantly correlated to the educational level and the treatment with antidepressant medication. A statistical analysis showed that longer stay period in the facilities correlates with current smoking, an effort to quit and increased belief that smoking causes harm to health. Further research on the attitudes of patients in residential facilities toward smoking is needed, which could guide interventions for smoking cessation and should be assumed by all health professionals who are involved in the care of those patients.
A hybrid boundary node method

A new variational formulation for boundary node method (BNM) using a hybrid displacement functional is presented here. The formulation is expressed in terms of domain and boundary variables, and the domain variables are interpolated by classical fundamental solution; while the boundary variables are interpolated by moving least squares (MLS). The main idea is to retain the dimensionality advantages of the BNM, and get a truly meshless method, which does not require a ‘boundary element mesh’, either for the purpose of interpolation of the solution variables, or for the integration of the ‘energy’. All integrals can be easily evaluated over regular shaped domains (in general, semi‐sphere in the 3‐D problem) and their boundaries.
Sustainable Development Goal interactions through a climate lens: a global analysis

Interactions between key Sustainable Development Goal (SDG) targets are synergetic at the global level when pursuing efforts to limit the temperature increase to 1.5°C, according to the authors' analysis. Their findings indicate two objectives are most beneficial for making progress on all other targets: making progress on mobilizing climate finance and Official Development Assistance (ODA) and mainstreaming climate change into national policy.
Algebraic Conditions for a Centre or a Focus in Some Simple Systems of Arbitrary Degree

Necessary and sufficient conditions are investigated, in the form of explicit algebraic formulas, for the origin to be a centre, an unstable focus, or a stable focus of a homogeneous polynomial planar vector field whose degree is arbitrary. This provides a unified treatment of the problem. The role of these conditions is exemplified in detail in the linear, cubic, and quintic cases. Similar considerations are provided for systems which possess homogeneous non-linearities and for which the origin is a uniformly isochronous centre.
ERROR ESTIMATES OF RT1 MIXED METHODS FOR DISTRIBUTED OPTIMAL CONTROL PROBLEMS

In this paper, we investigate the error estimates of a qua- dratic elliptic control problem with pointwise control constraints. The state and the co-state variables are approximated by the order k = 1 Raviart-Thomas mixed finite element and the control variable is dis- cretized by piecewise linear but discontinuous functions. Approximations of order h 3 2 in the L 2 -norm and order h in the L ∞ -norm for the control variable are proved.
Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development—a narrative review

Background and Objective Non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) driver alterations harbors a poor prognosis with standard therapies, including chemotherapy and/or immunotherapy with anti-programmed cell death protein 1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) antibodies. Selective KRAS G12C inhibitors have been shown to provide significant clinical benefit in pretreated NSCLC patients with KRAS G12C mutation. Methods In this review, we describe KRAS and the biology of KRAS-mutant tumors and review data from preclinical studies and clinical trials on KRAS-targeted therapies in NSCLC patients with KRAS G12C mutation. Key Content and Findings KRAS is the most frequently mutated oncogene in human cancer. The G12C is the most common KRAS mutation found in NSCLC. Sotorasib is the first, selective KRAS G12C inhibitor to receive approval based on demonstration of significant clinical benefit and tolerable safety profile in previously treated, KRAS G12C-mutated NSCLC. Adagrasib, a highly selective covalent inhibitor of KRAS G12C, has also shown efficacy in pretreated patients and other novel KRAS inhibitors are being under evaluation in early-phase studies. Similarly to other oncogene-directed therapies, mechanisms of intrinsic and acquired resistance limiting the activity of these agents have been described. Conclusions The discovery of selective KRAS G12C inhibitors has changed the therapeutic scenario of KRAS G12C-mutant NSCLC. Various studies testing KRAS inhibitors in different settings of disease, as single-agent or in combination with targeted agents for synthetic lethality and immunotherapy, are currently ongoing in this molecularly-defined subgroup of patients to further improve clinical outcomes.
An experimental study on grammatical sensitivity and production competence in Chinese and Spanish EFL learners and its implications on EFL teaching methods

Implicit knowledge acquired by L2 learners determines their language competence; however, it remains an issue to what extent advanced EFL learners can acquire implicit language knowledge. This study aims at finding out whether advanced EFL learners from two different L1s could acquire a level of implicit knowledge of English questions by using the modified Elicited Oral Imitation Task. A quantitative, experimental study with the Elicited Oral Imitation Task experimental tool was designed. A total number of 91 participants were recruited via the online experimental platform from October to November, 2021, distributed into a native speaker group, a Chinese EFL learner group, and a Spanish EFL group. The study evaluated participants’ implicit language knowledge by assessing two indicators: the grammatical sensitivity index and the production index. Independent-sample t-test and one-way analysis of variance (ANOVA) were applied to examine the differences in the two indices among different groups. Results revealed that both EFL groups displayed a significant difference with the native speaker group in their degree of implicit knowledge of English questions in general. A further comparison of the two indicators showed that while both EFL groups displayed a relatively high grammatical sensitivity to morpho-syntactic errors in English questions, their corrective production rate of ungrammatical sentences was notably lower. These results indicate that advanced EFL learners had difficulty in acquiring implicit knowledge of English questions at native speaker’ level. These findings also imply a gap between EFL learners’ language knowledge level and corresponding language production competence. Targeting this gap within the Interaction-based production-oriented approach pedagogical implications based on were suggested for enhancing EFL learners’ language production competence in EFL contexts.
Velocity Space of Galactic O-B Stars

Based on the Hipparcos proper motions and available radial velocity data of O-B stars, we have re-examined the local kinematical structure of the young disk population of ~1500 O-B stars not including the Gould-belt stars. A systematic warping motion of the stars about the direction to the Galactic center has been reconfirmed. A negative K-term implying a systematic contraction of stars in the solar vicinity has been detected. Two different distance scales are used in order to find out their impact on the kinematical parameters, and we conclude that the adopted distance scale plays an important role in characterizing the kinematical parameters at the present level of the measurement uncertainty.
A 3D-Printed Large Holding Capacity Device for Minimum Volume Cooling Vitrification of Embryos in Prolific Livestock Species

Simple Summary Commercially available devices with simultaneous vitrification of many embryos are scarce. In this study, we developed a new three-dimensional (3D)-printed device that combines minimum volume cooling vitrification with simultaneous vitrification of a larger number of embryos. The 3D technology was stereolithography, and the Cryoeyelet® device was printed in photosensitive resin. With the open Cryoeyelet®, 25 late rabbit morulae/early blastocysts were vitrified per device and compared with the Cryotop® and the French mini-straw devices. Our results demonstrate that the CryoEyelet® device can be used for the vitrification of a high number of late morulae or early blastocyst rabbit embryos per device, yielding similar outcomes to the most used commercial devices based on minimum essential volume. Abstract Although many devices have been developed to reduce sample volume, with an explosion of methods appearing in the literature over the last decade, commercially available devices with simultaneous vitrification of a larger number of embryos are scarce, with the apparent gap for their use in prolific livestock species. In this study, we investigated the effectiveness of a new three-dimensional (3D)-printed device that combines minimum volume cooling vitrification with simultaneous vitrification of a larger number of rabbit embryos. Late morulae/early blastocysts were vitrified with the open Cryoeyelet® device (n = 175; 25 embryos per device), the open Cryotop® device (n = 175; 10 embryos per device), and the traditional closed French mini-straw device (n = 125; 25 embryos per straw) and compared in terms of in vitro development and reproductive performance after transfer to adoptive mothers. Fresh embryos constituted the control group (n = 125). In experiment 1, there was no difference in the development rate to the blastocyst hatching stage between the CryoEyelet® and the other devices. In experiment 2, the CryoEyelet® device showed a higher implantation rate compared with the Cryotop® (6.3% unit of SD, p = 0.87) and French mini-straw® (16.8% unit of SD, p = 1.00) devices. In terms of offspring rate, the CryoEyelet® device was similar to the Cryotop® device but superior to the French straw device. Regarding embryonic and fetal losses, the CryoEyelet® showed lower embryonic losses compared to other vitrification devices. The analysis of bodyweight showed that all devices showed a similar outcomes—a higher birthweight but a lower body weight at puberty than those in the fresh transfer embryos group. In summary, the CryoEyelet® device can be used for the vitrification of many late morulae or early blastocyst stage rabbit embryos per device. Further studies should be performed to evaluate the CryoEyelet® device in other polytocous species for the simultaneous vitrification of a large number of embryos.