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An expression of partial wave expansion of three-baryon interactions in chiral effective field theory is presented. The derivation follows the method by Hebeler et al. [Phys. Rev. C{\bf 91}, 044001 (2015)], but the final expression is more general. That is, a systematic treatment of the higher-rank spin-momentum structure of the interaction becomes possible. Using the derived formula, a $\Lambda$-deuteron folding potential is evaluated. This information is valuable for inferring the possible contribution of the $\Lambda NN$ three-baryon forces to the hypertriton as the basis of further studies by sophisticated Faddeev calculations. A microscopic understanding of $\Lambda NN$ three-baryon forces together with two-body $\Lambda N$ interactions is essential for the description of hypernuclei and neutron-star matter., Comment: 7 pages, 4 figures. The version accepted for publication in Phys. Rev. C. The results of the numerical calculation have been revised

Malignant pleural mesothelioma (MPM) is an intractable disease with an extremely poor prognosis. Our clinical protocol for MPM of subablative radiotherapy (RT) followed by radical surgery achieved better survival compared to other multimodal treatments, but local relapse and metastasis remain a problem. This subablative RT elicits an antitumoral immune response that is limited by the immunosuppressive microenvironment generated by regulatory T (Treg) cells. The antitumor effect of immunotherapy to simultaneously modulate the immune activation and the immune suppression after subablative RT has not been investigated in MPM. Herein, we demonstrated a rationale to combine interleukin-15 (IL-15) superagonist (IL-15SA) and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonist (DTA-1) with subablative RT in mesothelioma. IL-15SA boosted the systemic expansion of specific antitumoral memory CD8+ T cells that were induced by RT in mice. Their effect, however, was limited by the up-regulation and activation of Treg cells in the radiated tumor microenvironment. Hence, selective depletion of intratumoral Treg cells through DTA-1 enhanced the benefit of subablative RT in combination with IL-15SA. The addition of surgical resection of the radiated tumor in combination with IL-15SA and DTA-1 maximized the benefit of RT and was accompanied by a reproducible abscopal response in a concomitant tumor model. These data support the development of clinical trials in MPM to test such treatment options for patients with locally advanced or metastatic tumors.

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma., Chan et al find that the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma that could explain their resistance to therapy. Blocking the GITR-GITRL pathway could therefore be a new therapeutic target for non-epithelioid mesothelioma.

BackgroundSystemic sclerosis (SSc) is an autoimmune disease that is characterized by systemic vasculopathy and fibrosis. Pulmonary hypertension (PH), defined as elevated pulmonary arterial pressure (PAP), is one of the leading causes of death of SSc1. In recent years, various therapies have been developed to target each of the pathogenesis of SSc – autoimmunity, vasculopathy, and fibrosis. Accordingly, treatment strategies based on risk stratification for PH progression are aspired; however, prediction of changes in PAP in diverse patients with SSc has not been established2.ObjectivesTo visualize the patterns of PAP elevation in SSc and to identify the clinical characteristics of each trajectory, by applying latent trajectory modeling for PAP measured repeatedly by echocardiography.MethodsThis was a multicenter, retrospective cohort study conducted at four referral hospitals in Kyoto, Japan. Patients with SSc who visited the study site between April 2008 and March 2021 and had at least three echocardiographic measurements of systolic pulmonary arterial pressure (sPAP) were included in this study. Follow-up concluded in March 2021. A group-based trajectory model3 was applied to the change in sPAP over time, and individual patients were classified into distinct subgroups that followed similar trajectories. The number and shape of the trajectories were estimated based on adequacy, goodness of fit, parsimony, and interpretability of the model. Clinical plausibility was assessed by comparing PH-free survival, i.e., time to either PH or death, for each trajectory. Multinomial logistic regression analysis was performed for baseline clinical characteristics associated with trajectory assignment.ResultsA total of 236 patients with a total of 1097 sPAP measurements were included. We identified five trajectories following the quadratic function as “rapid progression (n=9, 3.8%)”, “early elevation (n=30, 12.7%)”, “mid elevation (n=54, 22.9%)”, “late elevation (n=24, 10.2%)”, and “low stable (n=119, 50.4%)”. Each trajectory, in this order, showed earlier elevation of sPAP and shorter PH-free survival (Figure 1). In the multinomial logistic regression (with the “low stable” as reference), cardiac involvement was associated with the “rapid progression” (adjusted odds ratio [OR] 28.9, 95% confidence interval [CI] 3.21–259.5), diffuse cutaneous SSc was associated with the “early elevation” (OR 4.08, 95% CI 1.27–13.1), anti-centromere antibody positive was associated with the “mid elevation” (OR 4.50, 95% CI 1.11–18.2), and older age of onset was associated with the above three trajectories.ConclusionThe pattern of changes in pulmonary artery pressure over time in SSc can be classified into five distinct trajectories. Each trajectory differed in baseline clinical characteristics and outcomes.References[1]Pokeerbux MR, et al. Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature. Arthritis Res Ther. 2019;21(1):86.[2]Denton CP, et al. Systemic sclerosis. Lancet. 2017;390(10103):1685-1699.[3]Nagin DS, et al. Group-based trajectory modeling in clinical research. Annu Rev Clin Psychol. 2010;6:109-38.Disclosure of InterestsNone declared

M16, the Eagle Nebula, is an outstanding \HII \ region which exhibits extensive high-mass star formation and hosts remarkable "pillars". We herein obtained new $^{12}$CO $J=$1-0 data for the region observed with NANTEN2, which were combined with the $^{12}$CO $J=$1-0 data obtained using FUGIN survey. These observations revealed that a giant molecular cloud (GMC) of $\sim 1.3 \times 10^5$ \Msun \ is associated with M16, which is elongated by over 30 pc and is perpendicular to the galactic plane, at a distance of 1.8 kpc. This GMC can be divided into the northern (N) cloud, the eastern (E) filament, the southeast (SE) cloud, the southeast (SE) filament, and the southern (S) cloud. We also found two velocity components (blue and red shifted component) in the N cloud. The blue-shifted component shows a ring-like structure, as well as the red-shifted component coincides with the intensity depression of the ring-like structure. The position-velocity diagram of the components showed a V-shaped velocity feature. The spatial and velocity structures of the cloud indicated that two different velocity components collided with each other at a relative velocity of 11.6 \kms. The timescale of the collision was estimated to be $\sim 4 \times 10^5$ yr. The collision event reasonably explains the formation of the O9V star ALS15348, as well as the shape of the Spitzer bubble N19. A similar velocity structure was found in the SE cloud, which is associated with the O7.5V star HD168504. In addition, the complementary distributions of the two velocity components found in the entire GMC suggested that the collision event occurred globally. On the basis of the above results, we herein propose a hypothesis that the collision between the two components occurred sequentially over the last several $10^{6}$ yr and triggered the formation of O-type stars in the NGC6611 cluster., Comment: Accepted for publication on PASJ

Cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) can contribute to the benefit of hypofractionated radiation, but programmed cell death pathways (programmed cell death 1 and programmed cell death ligand 1 [PD-1/PD-L1]) may provide a mechanism of tumor immune escape. We therefore reviewed the influence of PD-1/PD-L1 and CD8+ TILs on survival after accelerated hypofractionated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma (MPM).Sixty-nine consecutive patients undergoing the protocol of Surgery for Mesothelioma after Radiation Therapy (SMART) between November 2008 and February 2016 were analyzed for the presence of PD-L1 on tumor cells, PD-1 on inflammatory cells, and CD8+ TILs. Comparison was made with a cohort of patients undergoing extrapleural pneumonectomy after induction chemotherapy (n = 14) and no induction (n = 2) between March 2005 and October 2008. PD-L1 expression on tumor cells ≥1% was considered positive. CD8+ TILs and PD-1 expression were scored as a percentage of positive cells.PD-L1 was negative in 75% of MPM after completion of SMART. CD8+ TILs ranged between 0.24% and 8.47% (median 2%). CD8+ TILs ≥2% was associated with significantly better survival in epithelioid MPM (median survival 3.7 years vs 2.3 years in CD8+ TILs2%; P = .02). PD-L1 positivity was associated with worse survival in biphasic MPM (median survival, 0.4 years vs 1.5 years in biphasic PD-L1 negative tumors; P = .07) after SMART. Multivariate analysis demonstrated that epithelioid MPM, nodal disease, and CD8+ TILs were independent predictors of survival after SMART.The influence of tumor microenvironment on survival differs between epithelioid and nonepithelioid MPM. CD8+ TILs is an independent factor associated with better survival in epithelioid MPM treated with SMART.

The expression of cytokines mRNA, including Interleukin (IL)-2, IL-4 and Interferon (IFN)-γ and lymphocyte proliferation stimulated in vitro with either Escherichia coli (E. coli) or Staphylococcus aureus (S.A.) by Peripheral Blood Mononuclear Cells (PBMC) obtained from Holstein dairy cows were examined after the onset of ketosis or milk fever of field cases during the lactation period. The cows were used 50 to 150 days after calving in this study and divided into three groups; seventeen cows with milk fever (MF Group, 94.9±8.6 days after calving), ten cows with ketosis (Ketosis Group, 96.3±10.2 days after calving) and twenty-seven cows with no clinical diseases (Control Group, 89.4±5.4 days after calving). PBMC were stimulated in vitro by soluble antigen of E. coli or S.A. together with recombinant IL-2. The numbers of the peripheral blood T cells and monocyte were lower in the Ketosis Group in comparison with those in the Control Group and a significant difference was found in the number of CD3 + TcR1-N12 + T cells. There was a significantly lower lymphocyte proliferation stimulated with E. coli and S.A. in the Ketosis Group compared to that in the Control Group. Expression of IL-2, IL-4 and IFN-γ mRNA in PBMC stimulated with S.A. in the Ketosis Group was significantly lower than that in the Control Group, but these cytokine expression showed no group differences when PBMC were stimulated with E. coli. The present study demonstrated the onset of ketosis during the lactation period decreases reactivity of PBMC at least when they were stimulated with S.A in vitro.

In the collapsing phase of a molecular cloud, the molecular gas temperature is a key to understand the evolutionary process from a dense molecular cloud to stars. In order to know this, mapping observations in NH3 lines are required. Therefore, we made them based on the FUGIN (FOREST Unbiased Galactic plane Imaging survey with Nobeyama 45m telescope). The 6 maps were observed in NH3 (J,K) = (1,1), (2,2), (3,3) and H2O maser lines and obtained temperature maps; some show temperature gradient in a cloud. Additionally 72 cores were observed. These candidates were called as KAGONMA or KAG objects as abbreviation of KAgoshima Galactic Object survey with Nobeyama 45-M telescope in Ammonia lines. We show the results of two regions in W33 and discuss their astrophysical properties.

A new high flux density non-oriented electrical steel sheet (JNP Core) has been developed. The magnetic flux density of JNP Core is enhanced more than 0.02T compared to an existing high flux density material (JNE Core) with nearly identical iron losses. There are two kinds of Si amount materials (JNP5 and JNP7) with thicknesses of 0.35 and 0.50 mm as in conventional non-oriented electrical steel sheet. The new steel is characterized by an improvement in its recrystallization texture. JNP Core is thought to be suitable for lamination material of PM motors or induction motors due to its high flux density and low iron loss. An in-wheel IPM motor for EV was made and the motor performance was tested. The motor efficiency and torque was improved by applying JNP5 material instead of conventional electrical steel sheet. Furthermore, the efficiency of induction motors using JNP Core as stator lamination material improved by more than 1% in the case that the operating flux density is over 1.6T.

A theoretical study has been performed on a hematoporphyrin and its dimers which are components of Photofrin, a photosensitizer. Full geometry optimizations have been carried out using the PBEPBE functional and 6-31G(d) basis set. This combination gives better agreement with X-ray crystal data of porphyrin. Among the dimers studied, the C-C linked structure is found to have the highest stability. The predicted change of free energy (AG = -13.9kcal/mol) suggests that the interconversation of ester to ether would be thermodynamically favorable. The time-dependent density functional theory (TDDFT) studies show that Q-band absorption maxima undergo a less intense transition and low oscillator strength, indicating that dimers have activity when treated under higher dosage.

乳牛の潜在性ケトーシスは分娩後の負のエネンルギーバランス(NEB)、臨床型ケトーシスや第四胃変位の発生と関連があるが、潜在性ケトーシスの発生状況や発生要因、ケトン体以外の血中成分については不明な点が多い。乳牛の潜在性ケトーシスの病態を明らかにする目的で、潜在性ケトーシス牛(52頭)、臨床型ケトーシス牛(23頭)および対照牛(75頭)の血中成分を比較検討した。潜在性ケトーシス牛では対照牛に比べて血糖(GLU)が低値、βヒドロキシ酪酸(BHB)、遊離脂肪酸(NEFA)、トリグリセライド(TG)、βリポタンパク、総タンパク、アスパラギン酸アミノトランスフェラーゼ(AST)およびγグルタミルトランスペプチダーゼが高値を、また、臨床型ケトーシス牛に比べてGLU、HDLコレステロール、総コレステロールおよびリン脂質が高値、BHB、NEFA、TGおよびASTが低値を示した。さらに、潜在性ケトーシス牛ではBHBとNEFA、BHBやNEFAとASTとの間に正の相関、BHBとGLU、GLUとASTとの間に負の相関が認められた。これらのことから、潜在性ケトーシスはNEBと密接な関連があり、潜在性ケトーシス牛は対照牛に比べてNEBに起因した体脂肪動員や肝機能低下の程度が重度で、臨床型ケトーシス牛に比べてNEBの程度や持続時間および肝機能低下が軽度であることが示唆された。

We have been developing a two-stage plasma armature railgun as the first step to produce a multistage railgun system, which is considered as a promising tool to achieve hypervelocities. For successful operation of the two-stage railgun, three technical problems are addressed: the insulation between the two segmented rails, the formation of, and correct timing of, the ignition of the plasma armature in the second-stage railgun. Of these problems, the correct timing of the ignition of the plasma armature of the second-stage railgun will most significantly affect the performance of the two-stage railgun. A large increase in the projectile velocity has been obtained in the second-stage railgun by solving these technical problems, from 1.7 to 5.8 km/s.

summary Recently, various authors have proposed the interesting idea that occlusal force may be a principal factor in cervical lesions of the tooth. It is speculated that the lateral force in non-ideal mastication causes the tooth to bend and that the resulting tensile stress damages the enamel surface. In this study, we carried out stress analysis on the upper central incisor and the lower first molar using the plastic–elastic deformation theory with two-dimensional finite element method (FEM). The essential feature that the tensile yield strength is much smaller than the compressive one was taken into account. Our results suggested that oblique loading on the tooth stretches the enamel surface near the cemento-enamel junction and causes plastic deformation which eventually leads to the cervical lesion.

Fibrous lesions are common in the oral cavity, however, in infants they are rarely reported. We present three cases of palatal polyps in infants aged 2 days, 3 months and 7 months. In two cases, the treatment was surgical removal and in one case the polyp decreased in size and surgical removal was not required. In two infants, the diagnosis was confirmed histologically as fibroepithelial hyperplasia.

Exact expression of the Pauli exclusion operator Q in the nuclear matter calculation is presented. Numerical calculations of the G matrix with the exact Q operator are carried out by employing the Bonn B and a C NN potentials. It is observed that the exact treatment of the operator Q brings about non-negligible and attractive contributions to the binding energy.

The surface tension of molten silicon was measured using the electromagnetic levitation method under microgravity. The atmosphere was Ar-3 pct H2 purified by Pt asbestos and magnesium perchlorate. The partial oxygen pressure is estimated to be less than 1.1 × 10−14 Pa. The spherical droplet shape was controlled by changing the current ratio between a quadrupole coil and a dipole coil. The surface tension of molten silicon can be expressed by the equation $$\gamma = 735 - 0.074 (T - 1687)$$ where γ is the surface tension (in mN/m) and T is the temperature (in K). The value was measured over a wide range of temperatures, from 230 K below the melting point (1687 K) to 1890 K. The scatter of the measured surface-tension values is much less than that measured by conventional methods.

A tracer study was performed to assign a radical produced with UV irradiation on photocatalytically active BaTi 4 O 9 for water decomposition. BaTi 4 O 9 was reduced in H 2 and oxidized in 16 O 2 , 17 O 2 or 18 O 2 at different temperatures. The behavior of oxygen exchange was investigated by thermal gravimetric analysis and Raman spectroscopy. Electron magnetic resonance spectra showed that new signals with g ⊥ =2.038 and g ⊥ =2.026 due to hyperfine splitting of 17 O − with A ⊥ =19.1 G appeared when oxidized in 17 O 2 , in addition to normal signals with g ⊥ =2.018 and g ‖ =2.004. The radical is assigned to O − produced from surface lattice oxygen of BaTi 4 O 9 .

蹄病の乳牛におけるルーメンコンデイションと栄養代謝状態を明らかにする目的で、正常牛(37例)、蹄底潰瘍牛(51例)、蹄球びらん牛(10例)および趾間フレグモーネ牛(13例)において血中アンモニア(NH3)と乳酸(LA)濃度のほか、いくつかの血液生化学的検査を実施した。その結果、血中NH3濃度は蹄球びらん牛で、血中LA濃度は蹄底潰瘍牛と蹄球びらん牛で、いずれも正常牛に比べわずかに高値を示したが有意な差異はみられなかった。また、蹄底潰瘍牛では泌乳後期に血中NH3およびLA濃度が正常牛に比べ高値を示す傾向が認められた。各蹄病牛では正常牛に比べ血清総タンパク濃度が高値を、また、蹄底潰瘍牛や蹄球びらん牛では正常牛に比べ血清総コレステロール、アルブミンおよびカルシウム濃度が低値を示す傾向が認められた。これらのことから、蹄病牛のルーメンコンデイションは正常牛に比べ差異がみられなかったが、蹄底潰瘍牛や蹄球びらん牛では、正常牛に比べ飼料からのエネルギーやタンパク摂取量が不足しており、また、カルシウム代謝にも問題のあることが示唆された。

Adult T-cell leukemia (ATL) is characterized by infiltration of various tissues by circulating ATL cells, a finding often associated with a poor prognosis. Leukocyte migration from the circulation into tissues depends on integrin-mediated adhesion to the endothelium, and integrins are tightly regulated by several factors, such as chemokines. In this study, we focused on the interaction between chemokines and chemokine receptors on ATL cells to understand factors involved in ATL cell infiltration of lymphoid organs. We compared freshly isolated ATL cells from patients with and without lymphoid organ involvement for the expression of the chemokine receptor CCR7/EBI1, the functional receptor for secondary lymphoid-tissue chemokine (SLC), which is expressed at high levels by high endothelial venules of lymph nodes and Peyer's patches. Reverse transcriptase-polymerase chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal antibody (CCR7.6B3), revealed that ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4+CD45RO+ T cells and ATL cells from patients without lymphoid organ involvement. Consequently, significantly more ATL cells from patients with lymphoid organ involvement than control CD4+CD45RO+ T cells and ATL cells from patients without lymphoid organ involvement adhered to surfaces coated with ICAM-1 and SLC or EBI1-ligand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow conditions and migrated toward SLC or ELC at a low concentration (30 ng/ml). These findings suggest that increased CCR7/EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. (Blood. 2000; 30-38)

The pulsed MOS capacitor generation lifetime technique is used to determine the iron density in boron-doped silicon wafers. Effective generation lifetimes (/spl tau//sub g,eff/) are extracted from the Zerbst plots obtained from the measured capacitance-time (C-t) data. Upon thermal heating at 200/spl deg/C for 5 minutes and quenching to 23/spl deg/C, iron-boron (Fe-B) pairs dissociate into interstitial iron (Fe/sub i/) and substitutional boron (B). The post-heated /spl tau//sub g,eff/ decreases immediately after heating. As time elapses (pairing time t/sub p/ increases) after Fe-B dissociation, T/sub g,eff/ increases because Fe/sub i/ reforms into Fe-B pairs. It takes about four times the time constant (i.e., t/sub p//spl ap/4/spl tau/) of Fe-B pairing reaction before the post-heated /spl tau//sub g,eff/ recovers to the pre-heated /spl tau//sub g,eff/. An expression is developed to determine the iron density. The iron density obtained from this expression shows good agreement with that measured by deep-level transient spectroscopy.

The electrical conduction property of c-GaN films grown on GaAs(001) by RF-MBE has been studied in relation with the amount of the hexagonal phase inclusion, or cubic phase purity. In a high-phase-purity (93%) film, the electron concentration and mobility at 300 K are typically 8×1017 cm–3 and 110 cm2/V-s, respectively. It is known that a parallel conduction is occurring in which the high mobility region somewhat away from the hetero-interface dominates the conduction at higher currents. In a lower-phase-purity (75%) film, it is indicated that the low mobility region extends over the larger region of the film. Above the cubic phase purity of about 90%, the electron concentration rapidly decreases and the mobility rapidly increases by one or two orders of magnitudes, suggesting that the stacking faults are the major source of the carrier electrons and causing the scattering centers responsible for the low mobility region. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)