Necrotizing pneumonia caused by Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has high mortality rates and is currently a serious ...clinical issue. PVL is a two-component toxin (LukS-PV and LukF-PV). It can cause necrosis in target cells by forming pores consisting of an octamer comprised of LukS-PV and LukF-PV. However, considering the specificity of PVL towards several target cells and species, the specific effect of PVL remains controversial. Therefore, we focused on necrotizing pneumonia caused by PVL-positive S. aureus and clarified the effect of PVL on alveolar macrophages, which play a central role in innate immunity in the alveolar space. We constructed recombinant PVL (rPVL) components and stimulated alveolar macrophages isolated from rabbits to evaluate cytotoxicity and pro-inflammatory cytokine release. Recombinant LukS-PV (rLukS-PV), but not recombinant LukF-PV (rLukF-PV), induced pro-inflammatory cytokine release. Specifically, tumor necrosis factor (TNF)-α release was mediated by the C5a receptor (C5aR) expressed on rabbit alveolar macrophages, and the toxicity of rPVL, consisting of rLukS-PV and rLukF-PV, towards rabbit alveolar macrophages was mediated by the same receptor. Overall, our findings shed light on the C5aR-mediated cytotoxic effect of PVL on alveolar macrophages, which may be useful for understanding the mechanism of necrotizing pneumonia caused by PVL.
Slant contrast refers to a stereoscopic phenomenon in which the perceived slant of a test object is affected by the disparity of a surrounding inducer object. Slant contrast has been proposed to ...involve cue conflict, but it is unclear whether this idea is useful in explaining slant contrast at short stimulus presentations (<1 s). We measured both slant contrast and perceived inducer slant while varying the presentation duration (100–800 ms) of stereograms with several spatial configurations. In three psychophysical experiments, we found that (a) both slant contrast and perceived inducer slant increased as a function of stimulus duration, and (b) slant contrast was relatively stable across different test and inducer shapes at each short stimulus duration, whereas perceived inducer slant increased when cue conflict was reduced. These results suggest that at brief, not long stimulus presentations, the cue conflict between disparity and perspective plays a smaller role in slant contrast than other depth cues.
To explore the possibility of conducting online experiments on audiovisual crossmodal interaction, we investigated the temporal accuracy and precision of stimulus presentation in Lab.js. We measured ...the presentation time as well as the onset and offset timings of audiovisual stimuli in two experiments; we used three operating systems (Windows10, macOS, and iOS), three browsers (Chrome, Firefox, and OS native), and three network environments (external network, internal network, and local host). Results showed that most software environments—with the exception of iOS—provide reasonable precision, irrespective of the network environment. In contrast, the accuracy almost systematically varied depending on the combination of the operating system and the browser. These results suggest that Lab.js is suitable for audiovisual experiments to some extent if audiovisual synchronization lag is corrected based on the information provided by the Lab.js default plug-in, which can detect the user’s OS and browser. However, considering that typical user hardware/software environments are far more complex and diverse than that of this study, effective ways to control users’ experimental environments should be investigated in future studies to obtain reliable data in online experiments.
If voluntary action is followed by an effect with a short time delay, the time interval between action and effect is often perceived to be shorter than it actually is. This perceptual time ...compression is termed intentional binding or temporal binding. We investigated age-related changes in adulthood considering temporal binding and its dependence on action body parts (i.e., hand vs. foot). This experiment included 17 young adults (mean age: 21.71 ± 3.14 years) and 27 older adults (mean age: 74.41 ± 3.38 years). Participants performed a button press task using their index fingers (hand condition) or toes (foot condition). The results showed that older participants exhibited a strong time compression comparable to young participants in the voluntary condition. Older participants also showed a strong time compression in involuntary action, which was induced by a mechanical device, differently from young participants. In line with previous research, the present age-related differences in time compression considering involuntary action suggest that causal belief significantly influences event perception rather than the associated intention of action or sensory afferents. The present results also suggest that the nature of action body parts has no significant influence on temporal binding, independent of age group.
Depth contrast is a stereoscopic visual phenomenon in which the slant of an element is affected by that of adjacent elements. Normalization has been proposed to be a possible cause of depth contrast, ...but it is still unclear how depth contrast involves normalization. To address this issue, we devised stereograms consisting of a vertical test line accompanied by several inducer lines, like a three-dimensional variation of the well-known Müller–Lyer configuration. The inducer lines had horizontal binocular disparities that defined a stereoscopic slant about a horizontal axis with respect to the endpoints of the test line. The observer’s task was to adjust the slant of the test line about a horizontal axis until it appeared subjectively vertical. The results of two psychophysical experiments found that slant settings were affected by the slant of local inducers, but not by the overall slant of the whole stimulus. These results suggest that, at least for line patterns, the stereo system normalizes depth locally.
Oligometastasis is a state in which cancer patients have a limited number of metastatic tumors; patients with oligometastases survive longer than those with polymetastases. Extensive disease ...(ED)-small cell lung cancer (SCLC) is considered a systemic disease and a poor survival. This study investigated whether the concept of oligometastases is prognostic factor also applicable to patients with ED-SCLC.
We performed a retrospective study of 141 consecutive patients with ED-SCLC between 2008 and 2016. The patients were divided into four subgroups: group 1; patients with solitary metastatic site in one organ (n = 31), group 2; patients with 2-5 metastatic sites in one organ (n = 18), group 3; patients with over 6 metastases in one organ (n = 15), and group 4; patients with 2 or more metastatic organs (n = 77).
It was identified that 49 patients with ED-SCLC had oligometastases (groups 1 + 2) and 92 had polymetastases (groups 3 + 4). The prognoses of patients with ED-SCLC and oligometastases, defined as ≤5 metastases in a single organ, were significantly superior to those of patients with polymetastases 16.0 (95% CI, 11.0-21.0) months vs. 6.9 (95% CI, 6.0-7.8) months; p<0.001. 43 of 49 patients with ED-SCLC and oligometastases were relapsed after initial chemotherapy, and 38 (88%) experienced local recurrence.
Patients with ED-SCLC and oligometastases may have improved survival than those with polymetastases. As oligometastatic ED-SCLC tends to recur locally, local therapy combined with systemic chemotherapy may be a treatment option.
Weil-type zeta functions defined by the numbers of absolutely irreducible
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\mathrm {SL}_2
-representations of the figure
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knot group over finite fields are computed explicitly. They are ...expressed in terms of the congruence zeta functions of reductions of a certain elliptic curve defined over the rational number field. Then the Hasse-Weil type zeta function of the figure
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knot group is also studied. Its central value is written in terms of the Mahler measures of the Alexander polynomial of the figure
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knot and a certain family of elliptic curves.
We herein report the case of a 52-year-old man with stage IV lung adenocarcinoma. The patient was negative for epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated ...protein-like 4 (EML4) /anaplastic lymphoma kinase (ALK) rearrangement. He was treated with nivolumab as a third-line chemotherapy. After four cycles of nivolumab treatment, a partial response was observed in the brain and at the primary tumor site. Nivolumab treatment has been continued for 11 months without progression. Immunohistochemistry revealed that the programmed death-ligand 1 (PD-L1) expression was 0% (according to the tumor proportion score). Our case indicates that the efficacy of programmed cell death 1 inhibitors is not solely predicted by the PD-L1 status, and that immune checkpoint inhibitors might be effective for the treatment of central nervous system metastasis.
We have been investigating applications of a topology optimisation method with the level set method. In this study, to further enhance the applicability of the method, we investigate a topology ...optimisation method for three-dimensional scalar wave scattering problems which can be defined in an unbounded domain. To this end, the fast multipole boundary element method (FMBEM), which can deal with the unbounded domain accurately and efficiently, is implemented in the proposed optimisation method. A detail of the algorithm of the topology optimisation with the level set method and the FMBEM is presented. Also, a rigorous derivation of the topological derivative, which characterises the sensitivity of the objective function when an infinitely small spherical object appears, using spherical functions is presented. After validating the topological derivatives with approximated ones, we show the efficiency of the proposed optimisation method with a numerical benchmark. Through these numerical experiments, we conclude that the proposed topological optimisation with the level set method and the FMBEM can be applied to scattering problems in acoustics.
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