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Abstract Although perampanel (PER) has received approval as an antiseizure medication, reports quantifying its antiseizure effects using electroencephalography (EEG) remain scarce. In a previous study, we demonstrated that the interictal high gamma oscillation regularity (GOR) on scalp EEG is an excellent marker of epileptogenicity. Herein, we investigated whether the antiseizure effect of PER could be quantified through interictal GOR analysis of scalp EEG data. To investigate this, we examined the interictal GOR from 20 s of scalp EEG data before and after PER administration collected from five patients with epilepsy with focal seizures. Prior to PER administration, each patient presented with localized areas with high GOR consistent with brain lesions or seizure semiology. In all patients, the seizures improved following PER administration, and the localized high GOR, which is considered an epileptogenic focus, disappeared. These results indicate that interictal GOR analysis may be a useful tool for the quantitative assessments of the antiseizure effects of PER in focal epilepsy. Plain Language Summary This study explored whether perampanel (PER)'s antiseizure effects can be quantified using interictal high gamma oscillation regularity (GOR) analysis from scalp EEG data. Analyzing 20‐second EEG segments before and after PER administration in five patients with focal epilepsy, we found that high GOR areas, indicative of epileptogenic foci, disappeared following PER administration. The results suggest that interictal GOR analysis could effectively quantify the antiseizure effects of PER.

Abstract We aimed to establish a new method of obtaining femur anteroposterior radiographs from live rats. We used five adult male Sprague–Dawley rats and created a femoral fracture model with an 8 mm segmental fragment. After the surgery, we obtained two femoral anteroposterior radiographs, a novel overhead method, and a traditional craniocaudal view. We obtained the overhead method three times, craniocaudal view once, and anteroposterior radiograph of the isolated femoral bone after euthanasia. We compared the overhead method and craniocaudal view with an isolated femoral anteroposterior view. We used a two-sample t-test and intraclass correlation coefficient (ICC) to estimate the intra-observer reliability. The overhead method had significantly smaller differences than the craniocaudal view for nail length (1.53 ± 1.26 vs. 11.4 ± 3.45, p

Abstract The Josephson junction (JJ) is an essential element of superconducting (SC) devices for both fundamental and applied physics. The short-range coherent coupling of two adjacent JJs forms Andreev molecule states (AMSs), which provide a new ingredient to engineer exotic SC phenomena such as topological SC states and Andreev qubits. Here we provide tunneling spectroscopy measurements on a device consisting of two electrically controllable planar JJs sharing a single SC electrode. We discover that Andreev spectra in the coupled JJ are highly modulated from those in the single JJs and possess phase-dependent AMS features reproduced in our numerical calculation. Notably, the SC gap closing due to the AMS formation is experimentally observed. Our results help in understanding SC transport derived from the AMS and promoting the use of AMS physics to engineer topological SC states and quantum information devices.

The stress propagation for a three-dimensional elastic sphere under a diametric loading condition in the framework of the linear elastodynamics is revisited. By describing displacements in terms of scalar and vector potentials using the Helmholtz theorem, the Navier-Cauchy equation, the time evolution equation for displacements, is converted to the wave equation. The wave equation is Laplace transformed and further solved in spherical coordinates to develop the tabular expressions for displacement and stress in terms of modified spherical Bessel functions, and the coefficients are determined to satisfy the initial and boundary conditions. The obtained solutions are given in the form of an inverse Laplace transform. For the steady solution, the long-time limit of the obtained solutions is derived by using the final value theorem of the Laplace transform. The unsteady solutions are obtained by applying the residue theorem of complex analysis by adding a path with zero contribution in the complex plane. The obtained solution includes longitudinal and transverse waves, and also Rayleigh waves propagating on the surface. The origin of the von Schmidt wave is discussed as a reflected wave produced by the longitudinal wave travelling on the surface. It is also discussed that the wave is bent, unlike in the case of semi-infinite systems.

In this paper, I address the directionality issue posed by conversion in English through an investigation of category mismatch under VP-ellipsis, a less-studied type of ellipsis mismatch. For example, certain nouns, such as graduateN and sneezeN, allow the ellipsis of the VP headed by their morphologically related verbal counterparts, graduateV and sneezeV, but not vice versa. I argue that this kind of directional asymmetry, which would be mysterious under a purely semantic identity approach to ellipsis, based on truth-conditional equivalence and mutual entailment, is accounted for in terms of the syntactic identity condition to the effect that the structure of an ellipsis site must be properly contained within the structure of its intended antecedent expression. I will then use this syntactic account of category-mismatched VP-ellipsis as a critical probe into the internal syntax of zero-related N-V pairs and show that both N→V and V→N word-based derivations, in addition to the root-based derivation, must be admitted to account for conversion in English. To the extent that my proposed analysis is on the right track, the kind of asymmetries observed in N-V conversion furnishes an excellent testing ground for an abstract syntactic derivation for these morphologically related word pairs.

Abstract Although the identification of late adolescents with subthreshold depression (StD) may provide a basis for developing effective interventions that could lead to a reduction in the prevalence of StD and prevent the development of major depressive disorder, knowledge about the neural basis of StD remains limited. The purpose of this study was to develop a generalizable classifier for StD and to shed light on the underlying neural mechanisms of StD in late adolescents. Resting-state functional magnetic resonance imaging data of 91 individuals (30 StD subjects, 61 healthy controls) were included to build an StD classifier, and eight functional connections were selected by using the combination of two machine learning algorithms. We applied this biomarker to an independent cohort (n = 43) and confirmed that it showed generalization performance (area under the curve = 0.84/0.75 for the training/test datasets). Moreover, the most important functional connection was between the left and right pallidum, which may be related to clinically important dysfunctions in subjects with StD such as anhedonia and hyposensitivity to rewards. Investigation of whether modulation of the identified functional connections can be an effective treatment for StD may be an important topic of future research.

Josephson junctions have applications in quantum circuits but producing and controlling the coupling between junctions is challenging. The authors characterize the electronic transport properties of two adjacent Josephson junctions, demonstrating short-range coherent coupling indicative of a nonlocal Josephson effect.

Abstract Background Immune checkpoint blockade (ICB) therapies have changed the paradigm of cancer therapies. However, anti-tumor response of the ICB is insufficient for many patients and limited to specific tumor types. Despite many preclinical and clinical studies to understand the mechanism of anti-tumor efficacy of ICB, the mechanism is not completely understood. Harnessing preclinical tumor models is one way to understand the mechanism of treatment response. Methods In order to delineate the mechanisms of anti-tumor activity of ICB in preclinical syngeneic tumor models, we selected two syngeneic murine colorectal cancer models based on in vivo screening for sensitivity with anti-PD-1 therapy. We performed tumor-immune profiling of the two models to identify the potential mechanism for anti-PD-1 response. Results We performed in vivo screening for anti-PD-1 therapy across 23 syngeneic tumor models and found that CT-26 and Colon 26, which are murine colorectal carcinoma derived from BALB/c mice, showed different sensitivity to anti-PD-1. CT-26 tumor mice were more sensitive to the anti-PD-1 antibody than Colon 26, while both models show similarly sensitivity to anti-CTLA4 antibody. Immune-profiling showed that CT-26 tumor tissue was infiltrated with more immune cells than Colon 26. Genomic/transcriptomic analyses highlighted thatWnt pathway was one of the potential differences between CT-26 and Colon 26, showing Wnt activity was higher in Colon 26 than CT-26. . Conclusions CT-26 and Colon 26 syngeneic tumor models showed different sensitivity to anti-PD-1 therapy, although both tumor cells are murine colorectal carcinoma cell lines from BALB/c strain. By characterizing the mouse cells lines and tumor-immune context in the tumor tissues with comprehensive analysis approaches, we found that CT-26 showed “hot tumor” profile with more infiltrated immune cells than Colon 26. Further pathway analyses enable us to propose a hypothesis that Wnt pathway could be one of the major factors to differentiate CT-26 from Colon 26 model and link to anti-PD-1 response. Our approach to focus on preclinical tumor models with similar genetic background but different sensitivity to anti-PD-1 therapy would contribute to illustrating the potential mechanism of anti-PD-1 response and to generating a novel concept to synergize current anti-PD-1 therapies for cancer patients.

An outbreak of trichinellosis occurred in Japan in December 2016. All case-patients had eaten undercooked bear meat, from which Trichinella larvae were subsequently isolated. DNA sequencing analysis of the mitochondrial genes cytochrome c-oxidase subunit 1 and internal transcribed spacer 2 confirmed that Trichinella T9 had caused the outbreak.

Multiphase arterial spin labeling (ASL), which obtains the imaged slices with various postlabeling delays, allows for the noninvasive assessment of cerebral hemodynamics that cannot be adequately acquired by single-photon emission computed tomography (SPECT) imaging. We describe the clinical usefulness of multiphase ASL in a patient with symptomatic carotid stenosis by comparison with SPECT at rest using iodoamphetamine. A 75-year-old man was referred to our hospital with severe stenosis of the left internal carotid artery (ICA). While SPECT showed no significant laterality of cerebral blood flow (CBF), multiphase ASL demonstrated relatively delayed perfusion in the left ICA territory. The patient underwent stent placement for the left ICA stenosis. Postoperatively, while SPECT demonstrated no significant laterality of CBF, multiphase ASL revealed improved perfusion in the left ICA territory. This case showed that multiphase ASL could accurately evaluate the cerebral hemodynamic status which could not be detected using pre- and postoperative SPECT.

We report on half-integer Shapiro steps observed in a gate-tunable short ballistic InAs nanowire Josephson junction. We observed the Shapiro steps of the short ballistic InAs nanowire Josephson junction and found the half-integer steps in addition to the conventional integer steps. In this Josephson junction device the junction transmission can be varied with gate voltage. From measurements of the gate voltage and temperature dependences of the Shapiro steps, the origin of half-integer steps is assigned to the skewness of the current phase relation in the short ballistic Josephson junctions. These results will contribute to establish and control the superconductivity physics in the short ballistic semiconductor nanowires.

Bobaljik & Wurmband (2015) have recently developed a hypothesis that no language truly mixes wh-movement and wh-in-situ structures in its syntax, with seemingly optional wh-in-situ in a wh-movement language being analyzed as a question with declarative syntax. In this paper, we will present novel data from Colloquial Singapore English (CSE) which question this hypothesis. Instead of assuming that the Q-feature of the interrogative CWH head in a language must be specified in a binary manner (valued or unvalued), we will propose that this feature is underspecified in languages such as CSE. The proposed amendment is not only sufficiently restrictive to cover the type of languages predicted by B&W’s original hypothesis, but also flexible enough to accommodate languages with a mixed wh-system. We will further argue that contact-based explanations, though plausible, do not have to be taken as a reason for CSE to develop this specific trait, which could have developed under independent, non-contact situations. This position is supported by Malay and Ancash Quechua, two non-contact languages which nonetheless exhibit optional wh-in-situ like CSE.

Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) is a well-known anti-fibrosis agent in preclinical and clinical studies which exerts its effect via inhibition of TGF-β/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds to the proline binding site of the catalytic domain of PRS. Here, we characterized a new class of PRS inhibitor (T-3833261) that is carefully designed in a way that binds to the ATP site of the catalytic domain and does not disrupt binding of proline. The anti-fibrotic activity and the mechanism of action for T-3833261 on TGF-β-induced fibrotic assay were compared with those of HF in primary human skin fibroblast. We evaluated in vivo effect of topical application of T-3833261 and HF on TGF-β-induced fibrotic genes expression in mice. We found that T-3833261 suppressed TGF-β-induced α-smooth muscle actin (α-SMA) and type I collagen α1 (COL1A1) expression through the Smad3 axis in a similar fashion to HF. In vivo topical application of T-3833261 reduced the increase of fibrotic genes expression such as α-Sma, Col1a1 and Col1a2 by TGF-β intradermal injection to the ear of a mouse. We revealed that T-3833261 is more effective than HF under the conditions of high proline concentration, as reported in fibrotic tissues. These results suggest the potential of ATP competitive PRS inhibitors for the treatment of fibrotic diseases such as scleroderma.

We investigate the distribution of argument ellipsis in Persian in the context of the recent debate concerning the derivation of null arguments. Using sloppy/quantificational interpretations of elided arguments, we show that Persian exhibits subject-object elliptical asymmetries. We develop various arguments against the Verb-Stranding VP-ellipsis analysis of the subject-object asymmetry. We argue instead that the asymmetry in question is captured by the anti-agreement theory (Saito 2007). Our analysis predicts that the logical subject in Persian should be able to permit argument ellipsis when it is not in the position associated with φ-feature agreement. We show that this prediction is indeed borne out in several syntactic constructions whose inanimate plural subjects do not enter into an agreement relation with any functional head such as T. We also briefly explore one significant consequence of our analysis for the proper treatment of the so-called differential object marker –râ and conclude that this marker is the default morphological case in the technical sense of Marantz (1991).

Rats fed a semipurified diet supplemented with 3% (w/w) safflower oil [Saf, n-3 fatty acid deficient, high linoleic acid (18:2n-6)] through two generations exhibit decreased correct response ratios in a brightness-discrimination learning test compared with rats fed 3% perilla oil [Per, high α-linolenic acid (18:3n-3)]. This is associated with a decreased DHA (22:6n-3)-to-arachidonic acid (20:4n-6) ratio in brain lipids. In the first set of experiments, dietary oil was shifted from Saf to a mixture of 2.4% safflower oil plus 0.6% DHA after weaning (Saf-DHA), but all parameters measured in the learning test were essentially unchanged. Brain 22:6n-3 content of the Saf-DHA group reached that of the Per group but the levels of 20:4n-6 and docosatetraenoic acid (22:4n-6) did not decrease to those of the Per group at the start of the test. In the second set of experiments, dietary oil was shifted to a mixture of 0.6% safflower oil plus 1.2% oleic acid (OA) plus 1.2% DHA (Saf-OA-DHA group) with 18:2n-6 content comparable to that of the Per group. The Saf-OA-DHA group exhibited a learning performance similar to that of the Per group; brain 22:6n-3, 20:4n-6, and 22:4n-6 contents were also comparable to those of the Per group.These results indicate that the altered learning behavior associated with a long-term n-3 fatty acid deficiency is reversed by supplementing 22:6n-3 after weaning, when the levels of competing n-6 fatty acids in the diet and brain lipids are limited.