PD-1 blockade is highly effective in classical Hodgkin lymphomas (cHLs), which exhibit frequent copy-number gains of CD274 (PD-L1) and PDC1LG2 (PD-L2) on chromosome 9p24.1. However, in this largely ...MHC-class-I-negative tumor, the mechanism of action of anti-PD-1 therapy remains undefined. We utilized the complementary approaches of T cell receptor (TCR) sequencing and cytometry by time-of-flight analysis to obtain a peripheral immune signature of responsiveness to PD-1 blockade in 56 patients treated in the CheckMate 205 phase II clinical trial (NCT02181738). Anti-PD-1 therapy was most effective in patients with a diverse baseline TCR repertoire and an associated expansion of singleton clones during treatment. CD4
, but not CD8
, TCR diversity significantly increased during therapy, most strikingly in patients who had achieved complete responses. Additionally, patients who responded to therapy had an increased abundance of activated natural killer cells and a newly identified CD3
CD68
CD4
GrB
subset. These studies highlight the roles of recently expanded, clonally diverse CD4
T cells and innate effectors in the efficacy of PD-1 blockade in cHL.
Zr50-x/2Co50-x/2Alx (x = 0, 4, 7) alloys fabricated by water-cooled copper mold casting yields excellent mechanical properties like high strength and large plasticity. Al can reduce the stacking ...fault energy and simultaneously improve strength and yield strength of the alloys. With increasing Al content, the effect of grain refinement strengthening, solid solution strengthening and second phase precipitation strengthening are enhanced to a certain extent. The good plasticity of these alloys primarily originates from the dislocation entanglement at the end of dislocation pileup and the transformation-induced plasticity associated with B2-to-B33 deformation-induced martensitic transformation. Zr46.5Co46.5Al7 alloy shows the highest ultimate compressive strength of 1787 MPa, and the largest ultimate failure strain of more than 25%.
•Al element can effectively increase the strength of Zr50-x/2Co50-x/2Alx (x = 0, 4, 7) alloy.•The good plasticity mainly originates from dislocation entanglement and TRIP.•Comprehensive mechanical properties originate from the synergy of various strengthening mechanisms.
We present optical continuum lags for two Seyfert 1 galaxies, MCG+08-11-011 and NGC 2617, using monitoring data from a reverberation mapping campaign carried out in 2014. Our light curves span the ...ugriz filters over four months, with median cadences of 1.0 and 0.6 days for MCG+08-11-011 and NGC 2617, respectively, combined with roughly daily X-ray and near-UV data from Swift for NGC 2617. We find lags consistent with geometrically thin accretion-disk models that predict a lag-wavelength relation of τ ∝ λ4/3. However, the observed lags are larger than predictions based on standard thin-disk theory by factors of 3.3 for MCG+08-11-011 and 2.3 for NGC 2617. These differences can be explained if the mass accretion rates are larger than inferred from the optical luminosity by a factor of 4.3 in MCG+08-11-011 and a factor of 1.3 in NGC 2617, although uncertainty in the SMBH masses determines the significance of this result. While the X-ray variability in NGC 2617 precedes the UV/optical variability, the long (2.6 day) lag is problematic for coronal reprocessing models.
An investigation of the properties of HgCdTe films grown by MBE and devices made from such films are reported. Through the precise control of growth conditions and the screening of the Zn component ...of CZT(211)B substrates, high-quality HgCdTe films were successfully deposited onto the CZT(211)B substrates and characterized by x-ray diffraction rocking curve analysis and etch pit density analysis. X-ray rocking curve (422) reflection full-width at half-maximum (FWHM) of less than 15 arcsec was obtained for Hg
0.7
Cd
0.3
Te epitaxial films, and etch pit density (EPD) of about 2 × 10
4
cm
−2
was observed. At the same time, the relationship between the FWHM of the x-ray double-crystal rocking curve and EPD was confirmed. By optimizing the pretreatment process of the CZT(211)B substrate, a further significant reduction in HgCdTe macrodefect densities to 54 cm
−2
to 1000 cm
−2
was observed on CdZnTe, including occasional occurrences of very few or no large "void clusters" that are often observed. Planar p-on-n HgCdTe mid-wave infrared (MWIR) focal plane arrays (FPAs) were fabricated based on MBE in situ indium doping and arsenic ion implantation technology. The temperature-dependent performance of planar p-on-n MWIR FPAs shows that the device has the ability to operate at high temperature of about 140 K with high performance.
China is the world's biggest livestock producer, and has a rapidly expanding intensive livestock production in response to growing demand. The large size of the country and geographical dispersion of ...the livestock production systems means that animals are often transported long distances to slaughter. This study investigated perceptions of animal welfare issues by stakeholders in the Chinese transport and slaughter industry using utility scores and adaptive conjoint analysis. An initial workshop for experts in this field identified key concerns; these were then included in a questionnaire, which was distributed electronically to stakeholders. Stakeholders, particularly those with higher levels of education, were most concerned about the absence of pre-slaughter stunning and failure to maintain unconsciousness throughout the slaughter process. For all livestock species electrical stunning was considered the best method of stunning and blunt trauma the worst; for cattle and sheep stunning using a penetrating captive bolt was considered preferable to the use a percussive captive bolt. Other concerns considered very important were journey quality and livestock workers' experience and attitudes. Heat stress and closed-sided vehicles were of greater concern than cold stress. Loading facilities and journey length were considered of intermediate importance, while lairage and methods for catching chickens were of least concern. The importance of some welfare concerns, e.g. livestock having to remain standing during a journey, was more commonly recognised by stakeholders who reported a high level of knowledge and experience. Therefore, these welfare issues could be a focus for future training activities. Compared to respondents directly involved in livestock transport, respondents involved in teaching and researching within livestock production rated the presented animal welfare issues as more important. These results can be used to guide development of training programmes, animal welfare research, and certification and regulatory control to target challenges to animal welfare in livestock transport and slaughter in China.
This letter introduces a new technique of inkjet printing antennas on textiles. A screen-printed interface layer was used to reduce the surface roughness of the polyester/cotton material that ...facilitated the printing of a continuous conducting surface. Conducting ink was used to create three inkjet-printed microstrip patch antennas. An efficiency of 53% was achieved for a fully flexible antenna with two layers of ink. Measurements of the antennas bent around a polystyrene cylinder indicated that a second layer of ink improved the robustness to bending.
We report on the observations of an electron vortex magnetic hole corresponding to a new type of coherent structure in the turbulent magnetosheath plasma using the Magnetospheric Multiscale mission ...data. The magnetic hole is characterized by a magnetic depression, a density peak, a total electron temperature increase (with a parallel temperature decrease but a perpendicular temperature increase), and strong currents carried by the electrons. The current has a dip in the core region and a peak in the outer region of the magnetic hole. The estimated size of the magnetic hole is about 0.23 i (∼30 e) in the quasi-circular cross-section perpendicular to its axis, where i and e are respectively the proton and electron gyroradius. There are no clear enhancements seen in high-energy electron fluxes. However, there is an enhancement in the perpendicular electron fluxes at 90° pitch angle inside the magnetic hole, implying that the electrons are trapped within it. The variations of the electron velocity components Vem and Ven suggest that an electron vortex is formed by trapping electrons inside the magnetic hole in the cross-section in the M-N plane. These observations demonstrate the existence of a new type of coherent structures behaving as an electron vortex magnetic hole in turbulent space plasmas as predicted by recent kinetic simulations.
Gut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut ...homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption. Mice were gavaged with ~ 2.9 g/kg ethanol and four hours later given a ~ 12.5% TBSA full thickness scald injury. One day later, IECs were harvested and total RNA extracted for RNA-seq and miRNA-seq. RNA sequencing showed 712 differentially expressed genes (DEGs) (padj < 0.05) in IECs following alcohol and burn injury. Furthermore, miRNA sequencing revealed 17 differentially expressed miRNAs (DEMs) (padj < 0.1). Utilizing the miRNet, miRDB and TargetScan databases, we identified both validated and predicted miRNA gene targets. Integration of small RNA sequencing data with mRNA sequencing results identified correlated changes in miRNA and target expression. Upregulated miRNAs were associated with decreased proliferation (miR-98-3p and miR-381-3p) and cellular adhesion (miR-29a-3p, miR-429-3p and miR3535), while downregulated miRNAs were connected to upregulation of apoptosis (Let-7d-5p and miR-130b-5p) and metabolism (miR-674-3p and miR-185-5p). Overall, these findings suggest that alcohol and burn injury significantly alters the mRNA and miRNA expression profile of IECs and reveals numerous miRNA-mRNA interactions that regulate critical pathways for gut barrier function after alcohol and burn injury.
Nonlinear dynamical systems often have multiple stable states and thus can harbor coexisting and hidden attractors that may pose an inconvenience or even hazard in practical applications. Amplitude ...control provides one method to detect these coexisting attractors, and it explains the unpredictable and irreproducible behavior that sometimes occurs in carefully engineered systems. In this paper, two regimes of amplitude control are described to illustrate the method for detecting multistability and possible coexisting or hidden attractors.
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