Response Mode Research Articles

Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with driver-gene negative advanced non-small cell lung cancer

BackgroundNo definite conclusion has yet to be reached for immunotherapy beyond progression(IBP) of first-line immunotherapy as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles best response and progressive mode of first-line immunotherapy could affect the results.Patients and methodsThe clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles best response and progressive mode of first-line immunotherapy were also evaluated.ResultsBetween January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups in whole population. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p=0.047) 16.1m (16.1 vs 10.8 p=0.039), 16.3m (16.3 vs 10.9 p=0.029) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and oligo progression of first-line immunotherapy.ConclusionsThe clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and oligo progression in first-line was benefit.

Real-time and high-sensitive colorimetric sensor based on photonic crystal for amniotic fluid identification

In this study, we proposed a pH-responsive photonic crystal hydrogel sensor (PCHs) to conveniently and accurately recognize the amniotic fluid from urine of parturient women, which was constituted by three-dimensional polymethyl acrylamide (PMMA) array and optimized hydrogel. PMMA array was self-assembled by 180 nm monodispersed nanoparticles with vertical sedimentation method. The functional hydrogel containing N-acryloyl phenylalanine (APA), acrylamide (AM) and N, N'-methylene bis(acrylamide) (BIS) as co-monomer and crosslinking agent respectively, was photo-polymerized by the precursor under 365 nm UV light. This hydrogel significantly shrank or swelled corresponding to the acidity and alkalinity of the aqueous solution, which resulted in both the reflection peak position (λmax) of the prepared sensor and its structural color changing with the pH value. The λmax of PCHs redshifted from 514 nm to 606 nm in 60 s while the pH value of testing solution increased from 4.5 to 8.0, which exactly covered the pH value of amniotic fluid and urine. Correspondingly, its structure color gradually changed from pale-green to red ensuring their naked-eye determination. Furthermore, an extremely high sensitivity as 26.3 nm/pH of Δλmax was obtained which was linearly related to pH value. The prepared sensor possessed steady accuracy and extraordinary sensitivity compared with the pH test strip which was generally used in amniorrhexis diagnosis nowadays besides the advantages of the low cost, simple operation, rapid response and visual detection mode. The reliability of this PCHs was further confirmed by the real sample detection which relative standard deviation was below 5.0 %, suggesting its potential clinical applications.

Love wave propagation in a trigonal piezoelectric material layer of 32 crystal class

This paper analytically investigates the propagation characteristics of Love waves in a 32 trigonal piezoelectric layer resting on an elastic substrate. The governing electromechanical equations are derived and dispersion equations are obtained for two electrically open and short conditions. For a numerical study, a structure consisting of an α-quartz layer bonded onto a diamond substrate is considered. The influence of electrical boundary conditions on the mechanical and electrical responses is presented and discussed. The numerical results of dispersion curves indicate that phase velocities of all modes initiate at the shear wave velocity of the substrate and the phase velocity of the first mode approaches the velocity of the Bleustein–Gulyaev (BG) wave at high wavenumbers. Despite hexagonal piezoelectric material, the real and imaginary parts of the response mode shapes do not have identical distribution in a structure containing a piezoelectric material of crystal class 32. In addition, the present study provides a theoretical foundation for the design and application of surface acoustic wave (SAW) devices.

Caregiver reactions to babbling organize turn-taking interactions: Facilitative effects of vocal versus non-vocal responses.

Turn-taking interactions are foundational to the development of social, communicative, and cognitive skills. In infants, vocal turn-taking experience is predictive of infants' socioemotional and language development. However, different forms of turn-taking interactions may have different effects on infant vocalizing. It is presently unknown how caregiver vocal, non-vocal and multimodal responses to infant vocalizations compare in extending caregiver-infant vocal turn-taking bouts. In bouts that begin with an infant vocalization, responses that maintain versus change the communicative modality may differentially affect the likelihood of further infant vocalizing. No studies have examined how caregiver response modalities that either matched or differed from the infant acoustic (vocal) modality might affect the temporal structure of vocal turn-taking beyond the initial serve-and-return exchanges. We video-recorded free-play sessions of 51 caregivers with their 9-month-old infants. Caregivers responded to babbling most often with vocalizations. In turn, caregiver vocal responses were significantly more likely to elicit subsequent infant babbling. Bouts following an initial caregiver vocal response contained significantly more turns than those following a non-vocal or multimodal response. Thus prelinguistic turn-taking is sensitive to the modality of caregivers' responses. Future research should investigate if such sensitivity is grounded in attentional constraints, which may influence the structure of turn-taking interactions.

Are minimally verbal autistic children's modality and form of communication associated with parent responsivity?

Prior work examined how minimally verbal (MV) children with autism used their gestural communication during social interactions. However, interactions are exchanges between social partners. Examining parent-child social interactions is critically important given the influence of parent responsivity on children's communicative development. Specifically, parent responses that are semantically contingent to the child's communication plays an important role in further shaping children's language learning. This study examines whether MV autistic children's (N = 47; 48-95 months; 10 females) modality and form of communication are associated with parent responsivity during an in-home parent-child interaction (PCI). The PCI was collected using natural language sampling methods and coded for child modality and form of communication and parent responses. Findings from Kruskal-Wallis H tests revealed that there was no significant difference in parent semantically contingent responses based on child communication modality (spoken language, gesture, gesture-speech combinations, and AAC) and form of communication (precise vs. imprecise). Findings highlight the importance of examining multiple modalities and forms of communication in MV children with autism to obtain a more comprehensive understanding of their communication abilities; and underscore the inclusion of interactionist models of communication to examine children's input on parent responses in further shaping language learning experiences.

Effect of impact spacing on the dynamic response of UHMWPE fiber composites under two-point high velocity impacts

The impact from multiple bullets leads to more severe damage to fiber composite laminates, and the dynamic response becomes more complex. However, current research has focused on studying the ballistic limit and single impact response of materials. In this study, an experimental method to investigate the dynamic response and damage modes of fiber composite materials under multi-point asynchronous impacts is proposed. The aim is to reveal the mechanisms behind the differences in ballistic limits and energy absorption of UHMWPE (Ultra-High Molecular Weight Polyethylene) fiber composite panels at different impact distances. Through CT scanning and DIC (Digital Image Correlation) techniques, the delamination area and dynamic response of the laminates were quantitatively analyzed. The results show that the ballistic limit of the second impact is increased by 3.05 % when the impact distance is 2.5 times the diameter of the bullet. The maximum difference of energy absorption compared to the first impact was only 3.7 % at an impact spacing of 5 times the diameter of the bullet, despite the interference in the damage region. From the perspective of energy absorption, the two impacts are independent. Multiple impact tests are critical for protective materials, and the results of this study provide important insights into UHMWPE fiber laminates in terms of multi-point impact.

IL-12 induces a B cell-intrinsic IL-12/IFNg feed-forward loop promoting extrafollicular B cell responses

Abstract While some infections elicit germinal centers (GC), others produce only extrafollicular (EF) responses. The mechanisms controlling these dichotomous fates are poorly understood. We identify IL-12 as a cytokine switch, acting directly on B cells to promote EF and suppress GC responses. IL-12 initiates a B cell intrinsic feed-forward loop between IL-12 and IFNg, amplifying IFNg production, which promotes proliferation and plasmablast (PB) differentiation, in synergy with IL-12. IL-12 sustains the expression of a portion of IFNg-inducible genes. Together, they also induce unique gene changes, reflecting both IFNg-amplification and cooperative effects between both cytokines. In vivo, cells lacking both IL-12 and IFNg receptors are more impaired in PB production than those lacking either receptor alone. Further, B cell-derived IL-12 enhances both PB responses and TH1 commitment. Thus, B cell-derived IL-12, acting on T and B cells, determines the immune response mode, with implications for vaccines, pathogen protection and autoimmunity.

Should We Offer Web, Paper, or Both? A Comparison of Single- and Mixed-Response Mode Treatments in a Mail Survey

Abstract This article leverages a five-treatment response mode experiment (paper-only, web-only, sequential web-mail, choice, and choice-plus [choice with a promised incentive for responding online]) that was conducted within a nationally representative survey. Because this survey’s sample was drawn from respondents to another nationally representative survey, we have rich frame data that includes multiple indicators of comfort using the internet for our sample members and we can compare their response behavior across two surveys. We find that the paper-only treatment yielded a lower response rate than most of the other treatments, but there were not significant differences between the response rates for the other treatments. Among our mixed-mode treatments, the sequential web-mail treatment had the highest percentage of response by web and the lowest cost per response. When focusing on the subgroups that we expected to be the least—and the most—comfortable with the internet, we found that the paper-only treatment generally performed worse than the others, even among subgroups expected not to be comfortable with the internet. We generally did not find significant differences in the effect of response mode treatment on the response rate or percentage of response by web between the subgroups who were the most and least comfortable with the internet. In terms of the consistency of response mode choice over time, our results suggest that some people respond consistently—but also that response mode preferences are weak enough that they can be influenced by the way in which the modes are offered. We ultimately recommend using a sequential web-mail design to minimize costs while still providing people who cannot or will not respond by web with another response mode option. We also find evidence that there may be a growing lack of interest in responding by paper; more research is needed in this area.

Progressive failure analysis of z-pin reinforced composite pi joints

A finite element model of a z-pin reinforced composite pi joint has been developed and correlated against experimental results. A smeared cohesive zone modeling approach was implemented to represent the effect of z-pinning in an efficient and scalable manner. In the smeared approach, cohesive properties governing the traction–separation response of the z-pin reinforced areas were defined to account for the effective fracture toughness caused by z-pinning in an averaged sense. The crack band method was used to account for diffuse damage and failure in the weave of the pi preform. The damage in the preform developed due to delamination suppression caused by the z-pinning. The numerical model was calibrated using experimental data from pristine and defective z-pinned pi joints subjected to pull-off and side-bend loading. Comparisons of experimental and numerical results show good agreement in terms of structural response, critical loads, and failure modes.

Gender stereotypes, patriarchal beliefs, and normative generics: A survey-based measure of what Polish parents communicate in norm-breaching scenarios involving children

Normative generics, which are statements that can be seen as reflecting the social world, can be powerful tools by which parents convey norms to children. In this article, we explored how two interrelated issues, the perceived salience of gender stereotypes and the socially constructed system of patriarchy, could affect what parents communicate in the context of parent–child interactions that concern the breaching of a salient gender norm. By analyzing data from two perception studies, we found that some norms pertaining to hair length or table manners triggered a more frequent use of normative generics than other norms and that the individuals who espoused traditional gender values tended to prefer one mode of norm responsiveness (i.e., norm-following) and used more normative generics than those espousing nontraditional gender norms. In this way, the study contributed to our understanding of how rules of behavior shared by members of a given group, as well as beliefs in a system of hierarchical power, might favor the use of normative generics.

Synthetic protein circuits for programmable control of mammalian cell death

Natural cell death pathways such as apoptosis and pyroptosis play dual roles: they eliminate harmful cells and modulate the immune system by dampening or stimulating inflammation. Synthetic protein circuits capable of triggering specific death programs in target cells could similarly remove harmful cells while appropriately modulating immune responses. However, cells actively influence their death modes in response to natural signals, making it challenging to control death modes. Here, we introduce naturally inspired "synpoptosis" circuits that proteolytically regulate engineered executioner proteins and mammalian cell death. These circuits direct cell death modes, respond to combinations of protease inputs, and selectively eliminate target cells. Furthermore, synpoptosis circuits can be transmitted intercellularly, offering a foundation for engineering synthetic killer cells that induce desired death programs in target cells without self-destruction. Together, these results lay the groundwork for programmable control of mammalian cell death.

Ultrasensitive and On‐Site Detection of Nitroaromatic Explosives Through a Dual‐Mode Hydrogel Sensor Utilizing Portable Devices

AbstractThe development of straightforward and dependable explosive sensors for on‐site identification is essential to preserving public safety concerns and lowering the safety risks related to explosions. However, one of the main barriers to the advancement of on‐site explosives detection in the future is the complexity of detection process. Here, a flexible hydrogel‐based sensing platform based on 3,4‐bis (4‐(1,2,2‐triphenylvinyl) phenyl) thiophene (TPE‐Z) and a methyl red design concept is shown that simultaneously achieves all targeted properties, including being quick, portable, reliable, and resistant to external interference. This composite fluorescent probe demonstrates outstanding detection capabilities, including low detection limits (0.48 mg L−1) and rapid response times (<5 s), which can be combined with smartphones for on‐site 2,4,6‐trinitrophenol (picric acid, PA) detection. Two independent fluorescence and colorimetric channels on the sensor showed selective response to PA under fluorescence and visible light irradiation, respectively. Meanwhile, the hydrogel sensor's distinct “turn on” and “turn off” response modes to PA can be utilized to construct “YES” and “NO” logic gates, which subsequently proves that they can be employed to differentiate PA on‐site. This sensing platform based on hydrogel is envisaged to offer in‐depth insights in advancing the on‐site detection of nitroaromatic explosives.

Dispersive nonreciprocity between a qubit and a cavity.

The dispersive interaction between a qubit and a cavity is ubiquitous in circuit and cavity quantum electrodynamics. It describes the frequency shift of one quantum mode in response to excitations in the other and, in closed systems, is necessarily bidirectional, i.e., reciprocal. Here, we present an experimental study of a nonreciprocal dispersive-type interaction between a transmon qubit and a superconducting cavity, arising from a common coupling to dissipative intermediary modes with broken time reversal symmetry. We characterize the qubit-cavity dynamics, including asymmetric frequency pulls and photon shot noise dephasing, under varying degrees of nonreciprocity by tuning the magnetic field bias of a ferrite component in situ. We introduce a general master equation model for nonreciprocal interactions in the dispersive regime, providing a compact description of the observed qubit-cavity dynamics agnostic to the intermediary system. Our result provides an example of quantum nonreciprocal phenomena beyond the typical paradigms of non-Hermitian Hamiltonians and cascaded systems.

Crashworthiness of AAG joints with a foam aluminum layer gusset plate

The gusset joint is the most widely used joint system in an aluminum alloy single-layer reticulated shell structure; it plays a vital role in the spatial grid structure. In this paper, the effects of different thicknesses of aluminum alloy gusset plates on the dynamic response and failure modes of aluminum alloy gusset (AAG) joints were studied by impact tests of three specimens. The test results show that the failure modes of AAG joints are a slight depression of the gusset plate, the local buckling of members, the local distortional buckling of members, and tearing of the lower flange and a web of members. The AAG joint inclines along the direction of the failed member and collapses. The finite element model of the AAG joint was established using ANSYS software. The stress, displacement, and deformation modes in the test and numerical simulation results were compared and analyzed, and the rationality of the numerical simulation results was verified. Based on the failure mode of the specimens, a design method for improving the impact resistance of AAG joints with aluminum foam layer gusset plate (AFLGP) is proposed. The numerical simulation results show that an AAG joint with an AFLGP effectively reduces the maximum peak value of impact loads through the deformation of the aluminum foam. In the elastic and elastic-plastic stages, AAG joint with AFLGP had better impact resistance, and the energy absorbed by its rods was 25.44% ∼ 30.36% lower than that of AAG joints alone. Finally, the influence of the thickness of the AFLGP on the impact force and energy absorption of the AAG joint was studied. The aluminum foam gusset layer plate is approximately twice as thick as the aluminum alloy gusset plate had the best protection effect on the AAG joint.

Parametric study for structural performance of spliced hybrid deck beams with UHPC cast in place joints

Splice beams are considered a solution for some difficults in bridge construction and a method for repairing damaged beams. One of the most challenging aspects of this technique is avoiding bond failure between the spliced members. In this study, ultra-high performance concrete (UHPC) was used to splice three beam segments due to its superior performance. This paper investigate the effects of some parameters on the spliced beams by Finite Element Method using computer program ABAQUS. The study have two approaches, first one, a validation study to generate model agree with experimental test results of seven specimens were tested under three bending point load. The main variables being the depth of the joint, the presence of a shear key in the joint, the hybridization of reinforcement, and the addition of dowels in the joint. The model was simulated and achieved good convergence when compared with experimental results, considering the load-deflection response and failure mode. The second approach that investigated various parametric studies, such as reverse cyclic load, repeated cyclic load, thickness of the deck, type of interface joint, reinforcement ratio, strengthening by UHPC layer, and the loading pattern.

Generalized modality responses in primary sensory neurons of awake mice during the development of neuropathic pain.

Peripheral sensory neurons serve as the initial responders to the external environment. How these neurons react to different sensory stimuli, such as mechanical or thermal forces applied to the skin, remains unclear. Using in vivo two-photon Ca2+ imaging in the lumbar 4 dorsal root ganglion (DRG) of awake Thy1.2-GCaMP6s mice, we assessed neuronal responses to various mechanical (punctate or dynamic) and thermal forces (heat or cold) sequentially applied to the paw plantar surface. Our data indicate that in normal awake male mice, approximately 14 and 38% of DRG neurons respond to either single or multiple modalities of stimulation. Anesthesia substantially reduces the number of responsive neurons but does not alter the ratio of cells exhibiting single-modal responses versus multi-modal responses. Following peripheral nerve injury, DRG cells exhibit a more than 5.1-fold increase in spontaneous neuronal activity and a 1.5-fold increase in sensory stimulus-evoked activity. As neuropathic pain resulting from nerve injury progresses, the polymodal nature of sensory neurons intensifies. The polymodal population increases from 39.1 to 56.9%, while the modality-specific population decreases from 14.7 to 5.0% within a period of 5 days. Our study underscores polymodality as a significant characteristic of primary sensory neurons, which becomes more pronounced during the development of neuropathic pain.

Effects of Land-Use Type and Salinity on Soil Carbon Mineralization in Coastal Areas of Northern Jiangsu Province

Sea level rise due to glacier melting caused by climate warming is a major global challenge, but the mechanism of the effect of salinity on soil carbon (C) mineralization in different land types is not clear. The pathways by which salinity indirectly affects soil carbon mineralization rates need to be investigated. Whether or not the response mode is consistent among different land-use types, as well as the intrinsic links and interactions between soil microbial resource limitation, environmental stress, microbial extracellular enzyme activity, and soil carbon mineralization, remain to be demonstrated. In this paper, three typical land-use types (wetland, forest, and agroforestry) were selected, and different salinity levels (0‰, 3‰, 6‰, and 32‰) were designed to conduct a 125-day laboratory incubation experiment to determine the soil CO2 release rate, soil physicochemical properties, and soil enzyme activities, and to correlate C mineralization with biotic and abiotic factors. A correlation analysis of soil physical and chemical properties, extracellular enzyme activities, and carbon mineralization rates was conducted to investigate their intrinsic linkages, and a multiple linear regression of C mineralization at different sites was performed to explore the variability of mineralization among different site types. Structural equation models were established in the pre- and post-incubation stages to study the pathways of soil C mineralization at different incubation times, and the mechanism of mineralization was further verified by enzyme stoichiometry. The results showed that, at the end of 125 days of incubation, the 32‰ salinity addition reduced the cumulative mineralization of forest and agroforestry types by 28.41% and 34.35%, respectively, compared to the 0‰ salinity addition. Soil C mineralization in the three different land-use types was highly correlated with the active C fractions of readily oxidizable C (ROC), dissolved organic C, and microbial biomass C (MBC) in the soil, with the standardized coefficients of multivariate linear regression reaching 0.67 for MBC in the wetland and −0.843 for ROC in the forest. Under long-term salinity additions, increased salinity would reduce the microbial respiratory quotient value by inhibiting β-glucosidase activity, thus indirectly affecting the rate of CO2 release. With added salinity, the mineralization of non-saline soil was more susceptible to the inhibitory effect of salinity, whereas the mineralization of salinized soil was more controlled by soil C pools.

The effect of response modality on witness statements when using the self-administered interview

The Self-Administered Interview (SAI©) elicits comprehensive initial statements from witnesses and can enhance subsequent statements. However, the SAI© requires a written response that may have disadvantages compared to a spoken account. This study tested the effect of SAI©’s response modality and its subsequent impact on a delayed retrieval attempt. After watching a mock crime, participants completed a Spoken-SAI©, Typed-SAI© or no-SAI©. Four days later, participants read a news report with misleading post-event information (PEI) and, after another 3 days, completed a free recall and a recognition test. The Spoken-SAI© required less time to be completed than the Typed-SAI© but elicited accounts with a comparable amount of correct information and accuracy. Providing an initial account using the SAI© (vs. no-SAI©) produced more detailed accounts 1 week later regardless of response modality but did not reduce the susceptibility to misleading PEI. This provides valuable insight for improving the SAI© and its applicability.

The contribution of higher order modes in the dynamic response of slender vertical structures with application to wind turbine towers

Understanding the contribution of the vibration modes to the response of a tower-like structure subjected to base excitations is crucial for a safe and optimized design. The modal contributions to the structural response are generally assessed through modal participation factors and effective masses; however, relatively recent studies pointed out the variability of the modal contributions depending on the response effect (e.g., top displacement, base shear force, base bending moment). The formulation proposed here derives the shear force and the bending moment at the base of a tower-like structure by combining the influence function technique with the quasi-static equivalent forces technique. The resulting formulation of the tower response relies on the concept of modal contribution factors, which provides a straightforward indication of the modal contributions associated with a given response effect. The proposed methodology is applied to the case of wind turbine towers erected on temporary foundations at the port quayside without rotor nacelle assembly to assess the forces on the foundations due to the seismic loading on the towers. This technique may be of great relevance for assessing the tower integrity during installation and for the design of the temporary foundations at the quayside of harbors in seismic area, also considering the quick expansion of the offshore wind energy in countries prone to earthquakes.

How urbanization shapes the ecosystem carbon sink of vegetation in China: A spatiotemporal analysis of direct and indirect effects

Rapid urbanization has led to extensive effects on the spatio-temporal patterns of the carbon sources and sinks in ecosystems. However, due to the lack of long-term continuous land use/cover change (LUCC) data, there has been limited discussion on the spatio-temporal impacts of urbanization on carbon sources/sinks and the non-linear characteristics of urban changes over time. This study focused on the impact of urbanization on vegetation net ecosystem productivity (NEP) in 31 provincial capital cities in China from 1990 to 2019, using land use change data and NEP indicators, to analyze the change patterns and response modes of urbanization intensity and NEP. The study found that: (1) During the period of 1990–1995, almost all cities in China experienced a turning point of urbanization rate from decreasing to increasing, while after 2000, the urbanization rate declined significantly; (2) Climate background affects the negative impact of urbanization on NEP, especially in warm and humid climate background, while the direct impact of urbanization on vegetation is more significant; (3) Overall, urbanization in China aggravated the negative impact of urbanization on NEP from 1990 to 2019, especially in cold and arid climate background, which would further exacerbate the negative impact of urbanization. This study helps us better understand the impact of Chinese urbanization on ecosystem carbon sinks and mitigating the carbon emissions pressure of urban environments.