Search

he correlation between neutral hydrogen (H i) in the intergalactic medium (IGM) and galaxies attracts great interest. We select four fields that include several coherently strong Lyα absorption systems at z ∼ 2.2 detected using background quasars from the whole SDSS/(e) Baryon Oscillation Spectroscopic Survey (BOSS) database. Deep narrowband and g-band imaging are performed using the Hyper Suprime-Cam on the Subaru Telescope. We select 2642 Lyα emitter (LAE) candidates at z = 2.177 ± 0.023 down to the Lyα luminosity of LLyα ≈ 2 × 1042 erg s−1 to construct the galaxy overdensity maps, covering an effective area of 5.39 deg2. Combining the sample with the Lyα absorption estimated from 64 (e) BOSS quasar spectra, we find a moderate to strong correlation between the LAE overdensity δLAE and the effective optical depth τLoS in lines of sight, with P value = 0.09% or

This chapter describes the academic knowledge needed in the design and operation of power plants. In both thermal and nuclear power plants, thermal energy is transferred to mechanical energy. Efficiency to convert the thermal energy to the mechanical energy is hence very important in power plants. Basic laws of energy conversion are discussed in Section 3.1: Thermodynamics. In the power plants, the heat is transferred to working fluid such as water, helium, and liquid sodium. After receiving the heat, the working fluid is conveyed to turbine to generate electricity. The fluid flow and heat transfer are hence important fundamental processes encountered in the power plants. These are discussed in Section 3.2: Fluid Dynamics and Section 3.3: Heat Transfer, respectively. The academic knowledge discussed in Sections 3.1–3.3 is commonly important in the thermal and nuclear power plants. The most essential difference between the thermal and nuclear power plants is the heat generation method. The heat is generated by fuel combustion in the thermal power plants and by nuclear reaction in the nuclear power plants. The basic principles of combustion and nuclear reaction are discussed in Section 3.4: Combustion and Section 3.5: Nuclear Physics, respectively.

We present the environmental properties around high-$z$ radio galaxies (HzRGs) at $z\sim4$, which have been poorly investigated because of their rarity. We use the largest samples of HzRGs and $g$-dropout galaxy overdense regions at $z\sim4$, which were constructed from Hyper Suprime-Cam Subaru Strategic Program, to characterize the HzRG environments statistically. We measure the $g$-dropout galaxy overdensities around 21 HzRGs whose rest-frame 1.4 GHz radio luminosities ($L_{1.4\mathrm{GHz}}$) are $10^{26-27}$ W Hz$^{-1}$. We find that the overdensities around the faint HzRGs with $L_{1.4\mathrm{GHz}}\sim10^{26.0-26.5}$ W Hz$^{-1}$ tend to be higher than that of the $g$-dropout galaxies. On the other hand, no significant difference of density environments is found between the luminous HzRGs with $ L_{1.4\mathrm{GHz}}\sim10^{26.5-27.0} $ W Hz$^{-1}$ and the $g$-dropout galaxies. The HzRGs are found to occupy more massive halos than $g$-dropout galaxies through a cross-correlation between the HzRGs and $g$-dropout galaxies. This trend is more pronounced in the faint HzRGs. These results are consistent with a scenario where HzRGs get older and more massive as the radio-luminosity decreases. The HzRGs are expected to trace the progenitors of local cluster halos from their calculated halo mass. In addition, we find that surrounding galaxies tend to distribute along the radio-jet major axis of the HzRGs at angular distances less than $\lesssim500$ physical kpc. Our findings imply the onset of the filamentary structures around the HzRGs at $z\sim4$., Comment: 22 pages, 8 figures, accepted in ApJ

Characterizing high-z quasar environments is key to understanding the co-evolution of quasars and the surrounding galaxies. To restrict their global picture, we statistically examine the g-dropout galaxy overdensity distribution around 570 faint quasar candidates at z ~ 4, based on the Hyper Suprime-Cam Subaru Strategic Program survey. We compare the overdensity significances of g-dropout galaxies around the quasars with those around g-dropout galaxies, and find no significant difference between their distributions. A total of 4 (22) out of the 570 faint quasars, 0.7_{-0.4}^{+0.4} (3.9_{-0.8}^{+0.8}) %, are found to be associated with the > 4 sigma overdense regions within an angular separation of 1.8 (3.0) arcmin, which is the typical size of protoclusters at this epoch. This is similar to the fraction of g-dropout galaxies associated with the > 4 sigma overdense regions. This result is consistent with our previous work that 1.3_{-0.9}^{+0.9} % and 2.0_{-1.1}^{+1.1} % of luminous quasars detected in the Sloan Digital Sky Survey exist in the > 4 sigma overdense regions within 1.8 and 3.0 arcmin separations, respectively. Therefore, we suggest that the galaxy number densities around quasars are independent of their luminosity, and most quasars do not preferentially appear in the richest protocluster regions at z ~ 4. The lack of an apparent positive correlation between the quasars and the protoclusters implies that: i) the gas-rich major merger rate is relatively low in the protocluster regions, ii) most high-z quasars may appear through secular processes, or iii) some dust-obscured quasars exist in the protocluster regions., 12 pages, 4 figures

The spatial inhomogeneity is one of the important features for understanding the reionization process; however, it has not yet been fully quantified. To map this inhomogeneous distribution, we simultaneously detect Ly$\alpha$ emitters (LAEs) and Lyman break galaxies (LBGs) at $z \sim 6.6$ from the Subaru/Hyper Suprime-Cam (HSC) large-area ($\sim1.5\,\mathrm{ deg}^2 = 34000\,\mathrm{cMpc}^2$) deep survey. We estimate the neutral fraction, $x_\mathrm{HI}$, from the observed number density ratio of LAEs to LBGs, $n(\mathrm{LAE})/n(\mathrm{LBG})$ based on numerical radiative transfer simulation, in which model galaxies are selected to satisfy the observed selection function. While the average $x_\mathrm{HI}$ within the field of view is found to be $x_\mathrm{HI} < 0.4$, which is consistent with previous studies, the variation of $n(\mathrm{LAE})/n(\mathrm{LBG})$ within the field of view for each $140\,\mathrm{pMpc}^2$ is found to be as large as a factor of three. This may suggest a spatially inhomogeneous topology of reionization, but it also leaves open the possibility that the variation is based on the inherent large-scale structure of the galaxy distribution. Based on the simulations, it may be difficult to distinguish between the two from the current survey. We also find that LAEs in the high LAE density region are more populate high $\mathrm{EW}_0$, supporting that the observed $n(\mathrm{LAE})/n(\mathrm{LBG})$ is more or less driven by the neutral fraction, though the statistical significance is not high., Comment: 20 pages, 22 figures, accepted for publication in ApJ

Introduction Extracellular signal-regulated kinase (ERK) modulates differentiation and maturation of adipocyte and the hypertrophy and differentiation of adipocytes affected the vascular diseases in obese. Changes in characters of adipocytes could develope the oxidative stress and inflammations. Moreover, changes in perivascular adipose tissue (PVAT) could modulate vascular tonus in obesity. However, the role of adipose ERK2 in endothelial function and characters of PVAT in obese in vivo had not been clarified, yet. Purpose This study aims to elucidate the role of the adipose ERK2 in endothelial-dependent relaxation (EDR) in mice model of obesity. The role of PVAT in EDR was also assessed. Methods and results We created adipose-specific ERK2 knock out mice (AE2KO) by crossing fatty acid binding protein 4 Cre and ERK2 flox mice and fed them with normal diet (ND) or high fat/ high sucrose diet (HFHSD) for 24 weeks. AE2KO fed with HFHSD gained more weight and revealed the heterogeneity in sizes of adipocyte in subcutaneous fat (SF). Furthermore, the mRNA levels of lipoprotein lipase, hormone-sensitive lipase, and peroxisome proliferator-activated receptor γ, which was the master genes of adipocyte differentiation, were markedly down-regulated in SF. PVAT in AE2KO with HFHSD was markedly enlarged and the mRNA expression of inflammatory adipocytokines, such as IL-1β and leptin were up-regulated. Next, we assessed EDR by acetylcholine (ACh) -induced relaxation in aortic rings with or without PVAT. EDR without PVAT was modestly decreased in AE2KO with HFHSD compared with wild type mice (WT) with HFHSD. Aortic rings with PVAT increased EDR in WT with ND. PVAT modestly decreased EDR in WT with HFHSD and mostly eliminated EDR in AE2KO with HFHSD. To assess the contraction factors released from PVAT, the solutions incubated with PVAT (SIP) were transferred to the normal aortic rings. SIP from WT with HFHSD mildly increased vascular tone and SIP from AE2KO with HFHSD further increased it. Tempol, which was superoxide scavenger, restored endothelial dysfunction with PVAT and suppressed the contraction with SIP from AE2KO with HFHSD. Fluorescence intensity of dihydroethidium stain of aorta and PVAT, which indicated that aortic and adipose superoxide production were elevated in AE2KO with HFHSD, which were mostly eliminated with tempol. Conclusions Adipose ERK2 selectively modulated differentiation in SF, suppressed the aortic oxidative stress and protected from endothelial dysfunction in obese. Moreover, adipose ERK2 suppressed the hypertrophy, inflammation, and oxidative stress of PVAT in obese. The oxidative stress with the inflammation in PVAT released vasoconstriction factors, which contributed to endothelial dysfunction in obese mice. Figure 1 Funding Acknowledgement Type of funding source: None

To assess the additional effects of intraoperative radiotherapy (IORT) with decompression surgery and adjuvant external beam radiotherapy (EBRT) for metastatic epidural spinal cord compression (MESCC). This single-arm institutional prospective observational study recruited patients between June 2017 and March 2020 and included those with symptoms of spinal cord compression owing to metastases, who were diagnosed using MRI. Patients with radiation-sensitive primary tumors and those who could not tolerate surgery were excluded. The treatment protocol comprised decompression surgery and electron beam IORT of 20 Gy in a single fraction followed by EBRT of 30 Gy in 10 fractions. The primary endpoints included the 1-year local failure rate and ambulatory functions. The study was closed in May 2019 owing to changes in treatment policies at our institution. Twenty patients were registered between June 2017 and May 2019. Although all patients completed surgery and IORT, 2 did not receive postoperative EBRT. Patients most commonly had colorectal cancer (4 patients), followed by thyroid cancer, renal cell carcinoma, lung cancer, breast cancer, sarcomas, and other cancers (3, 3, 2, 2, 2, and 4 patients, respectively). The median follow-up duration was 16 months (range 2–30 months); the 1-year local failure rate was 16%. On comparing ambulatory functions pre-treatment and at 1 year after treatment, improvement, no change, and worsening were observed in 3, 9, and 0 patients, respectively. This study’s findings suggest that decompression surgery and IORT followed by EBRT are effective in achieving local control and maintaining ambulation in patients with MESCC.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain., eLife digest Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons – compared to some 86 billion in humans – the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map – or connectome – the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Backgrounds: Right ventricular (RV) failure plays a critical role in right heart failure and left heart failure. However, there is no specific therapy developed for RV failure. To elucidate a novel therapeutic target against RV failure, we focus on RV specific genes to develop novel therapeutics for RV failure. Methods: Microarray analysis using several parts of adult murine heart was conducted and differentially expressed genes (DEGs) were applied to pathway analysis. Molecular mechanism was examined by using neonatal rat ventricular cardiomyocyte (NRVM) in vitro. To understand the function of target molecule in vivo, we induced RV failure by pulmonary artery constriction (PAC) in mice and inhibition experiments were performed using RV failure model. Results: In microarray analysis for RV, left ventricle and ventricular septum, 995 genes were extracted as DEGs in RV. Pathway analysis showed that alternative complement pathway-related genes were significantly up-regulated in RV. Moreover, complement factor D (Cfd) and C3a was a potential upstream factor attributable to unique feature of RV. Administration of C3a recombinant protein to NRVM phosphorylated several MAP kinases. In vivo, in C3KO PAC mice, RV dysfunction was significantly suppressed, and histological study showed that RV fibrosis was significantly suppressed. In wild type mice with PAC, administration of C3a receptor antagonist dramatically improved RV dysfunction and reduced RV fibrosis. Additionally, in vivo electrophysiological study revealed that the inducibility of ventricular arrhythmia was increased in wild type PAC mice, but ventricular arrhythmia was significantly attenuated in C3KO PAC mice. Furthermore, the expression of chemokine Ccl5 was enhanced in RV of wild type PAC mice, while Ccl5 was significantly attenuated in C3KO PAC mice. Conclusion: We revealed that complement C3a was highly produced in RV and chemical or genetical blockade of C3a ameliorates RV dysfunction and RV fibrosis in PAC mice. C3a was to be a potent bioactive protein for immunocompetent cells that played an important role in modulating cardiac function. Accordingly, we demonstrated that the blockade of C3a had a potential role for novel therapeutic target to RV failure.

BackgroundBecause of the lack of evidence on practice patterns of postoperative radiation therapy (PORT)in patients with metastases to the long bones, it is essential to characterize the current practice patterns and identify factors affecting dose-fractionation to aid future clinical trials. MethodsThe palliative radiation therapy subgroup of the Japanese Radiation Oncology Study Group conducted an internet-based survey to determine the prescription practices and various dose-fractionations used for PORT. Additionally, responders were asked to recommend dose-fractionations in four hypothetical cancer cases, wherein each case represented a patient with impending pathological fractures and one of the four features: limited prognosis, solitary metastasis, radio-resistant primary tumor, or long-term survival. Responders were asked to indicate their preferred irradiation fields and the reasons for choosing long-course radiotherapy over short-course radiotherapy (RT). ResultsEighty-nine radiation oncologists from 67 institutions and 151 RT plans were included. Twenty-two different dose-fractionations were used; the most commonly used and recommended dose-fractionation was 30 Gy in 10 fractions. “Local control” was most the common reason for preferring longer course RT. While fractionated higher-dose regimens were preferred in case of oligometastasis, low dose regimens were preferred in case of limited prognosis; single fraction RT was never preferred. Most respondents recommended involvement of “the entire orthopedic prosthesis.” ConclusionFor PORT of metastases to the long bones, 30 Gy in 10 fractions for the entire orthopedic prosthesis is preferred in current practice. Oligometastasis and a limited prognosis influence the selection of high- and low-dose regimens, respectively. Single fraction RT is never preferred.

Purpose The present multicenter, single-arm, phase 2 study aimed to prospectively evaluate the palliative efficacy of stereotactic body radiation therapy (SBRT) in patients with painful nonspine bone metastases. Methods and materials Patients with painful (≥2 points on a 0-to-10 scale) nonspine bone metastases from a solid tumor were enrolled. The prescribed dose was 35 Gy in 5 fractions. The primary endpoint was overall pain response rate (complete response [CR] and partial response [PR]) as measured per the International Consensus on Palliative Radiotherapy Endpoints guideline 6 months after SBRT. Results Forty-one osseous lesions in 38 patients were registered between June 2018 and June 2019. All lesions satisfied the inclusion criteria, and the patients completed the protocol treatment. Patients most commonly had lung cancer (22%), followed by prostate cancer, uterus cancer, and renal cell carcinoma (15%, 15%, and 12%, respectively). Bone metastases were most commonly located in coxal bones (56%). The median duration of follow-up after registration was 8 months (range, 1-19 months). Among evaluable lesions at 3 and 6 months after SBRT, the 3- and 6-month pain response rates were 78% and 75%, respectively. The local control rate at 6 months was 92%. Seven patients (17%) experienced bone fracture after irradiation, and 3 patients (7%) experienced grade 2 limb edema. One patient had regrowth of coxal bone metastases, and the tumor penetrated the sigmoid colon. Soft tissue abscess around the tumor and osteonecrosis of coxal bones were confirmed. The patient died of infection 4 months after SBRT and was determined to be a possible treatment-related death. Conclusions This prospective clinical trial showed that SBRT for nonspine bone metastases was effective in terms of pain palliation. These findings warrant a larger randomized controlled trial to compare SBRT with conventional radiation therapy. Additionally, operation history should be considered as a risk factor for edema.

Background Cavotricuspid isthmus (CTI) ablation for atrial flutter (AFL) shows a high success rate and effective for patients. However, operators experience difficulties in CTI ablation in some cases and need additional ablation for repeated recurrence. We investigated whether the SOUNDSTAR® (Biosense. Webster, Diamond Barr, CA, USA) catheter would be effective to select a CTI line of high therapeutic effect. Methods We have investigated the anatomy of around CTI by SOUNDSTAR® catheter and decided the CTI line using the anatomical information in AFL ablation (Figure1). We assumed two CTI lines of medial and lateral line. Medial CTI (M-CTI) line was more common and shorter line. Lateral CTI (L-CTI) line was uncommon and slightly longer line. We use 3.5mm tip catheter with NxT steerable introducer. The target Ablation Index (AI) was 400, and the target VisTtag™ interval was 6 mm or less. Results A total 30 of AFL ablated cases were investigated retrospectively. We surveyed 15 cases in M-CTI group and 15 cases in L-CTI group. Comparing the length of CTI in all cases, the length of M-CTI line was shorter than L-CTI line (M-CTI 32.1 ± 6.6mm vs. L-CTI 38.4 ± 8.3mm, n = 30, p Conclusions CTI ablation at the shorter distance M-CTI, which is commonly selected, resulted in more recurrences due to the unevenness including Eustachian ridge and the myocardium thickness. However, ablation at slightly longer L-CTI line showed lower recurrence and effective for CTI ablation. Abstract Figure 1

Background Sarcoplasmic reticulum Ca2+-ATPase2 (SERCA2) plays an important role in intracellular Ca2+ handling. Under pathological conditions, oxidative stress leads to irreversible oxidation of Cys674 on SERCA2 which causes intracellular Ca2+ overload. Intracellular Ca2+ overload is known as the cause of ventricular arrhythmia, but the relation between SERCA2 function and ventricular arrhythmia remains unclear. Purpose To investigate the role of Cys674 on SERCA2 in the intracellular Ca2+ handling and the induction of ventricular arrhythmia. Methods We employed SERCA2 Cys674Ser heterozygote knock-in mice (SKI) which mimics oxidative modification of Cys674 on SERCA2. Continuous infusion of angiotensin (ANG) (3mg/kg/day) or distilled water were performed both in wild type mice (WT) and SKI for a week. After 1 week, electrophysiological study and intracellular Ca2+ transient measurement were performed. Results ANG elevated blood pressure and represented cardiac hypertrophy with fibrosis similarly both in WT and SKI. The mRNA expression of calcium/calmodulin-dependent protein kinase-II (CaMKII), ryanodine receptor (RyR) and sodium-calcium exchanger (NCX) was increased in SKI heart compared with WT. QTc interval was prolonged in SKI compared with WT, which was markedly prolonged with ANG infusion. Under programmed electrical stimulation, only SKI with ANG showed high incidence of pacing induced ventricular arrhythmia (0/11 in WT/SKI control, 0/14 in WT with ANG vs. 8/14 in SKI with ANG, P Conclusions The loss of thiol on Cys674 under pathological condition resulted in impaired Ca2+ handling and high incidence of ventricular arrhythmia which were ameliorated by inhibition of Ca2+ leakage through RyR. Oxidative modification of Cys674 on SERCA2 might contribute to Ca2+ mishandling and arrhythmogenesis. Abstract Figure.

A 15-mm whitish, depressed lesion was observed in the stomach of a 39-year-old using screening esophagogastroduodenoscopy. The lesion had grown to a size of 40mm and had a cobblestone-like appearance at an 11-year endoscopic follow-up. Using endoscopic submucosal dissection (ESD) as a diagnostic therapy, gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 without Helicobacter pylori infection was detected. Although the patient did not undergo additional treatments, he remained alive without for recurrence 5 years after ESD.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.

Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms.

Summary Different types of Drosophila dopaminergic neurons (DANs) reinforce memories of unique valence and provide state-dependent motivational control [1]. Prior studies suggest that the compartment architecture of the mushroom body (MB) is the relevant resolution for distinct DAN functions [2, 3]. Here we used a recent electron microscope volume of the fly brain [4] to reconstruct the fine anatomy of individual DANs within three MB compartments. We find the 20 DANs of the γ5 compartment, at least some of which provide reward teaching signals, can be clustered into 5 anatomical subtypes that innervate different regions within γ5. Reconstructing 821 upstream neurons reveals input selectivity, supporting the functional relevance of DAN sub-classification. Only one PAM-γ5 DAN subtype γ5(fb) receives direct recurrent feedback from γ5β′2a mushroom body output neurons (MBONs) and behavioral experiments distinguish a role for these DANs in memory revaluation from those reinforcing sugar memory. Other DAN subtypes receive major, and potentially reinforcing, inputs from putative gustatory interneurons or lateral horn neurons, which can also relay indirect feedback from MBONs. We similarly reconstructed the single aversively reinforcing PPL1-γ1pedc DAN. The γ1pedc DAN inputs mostly differ from those of γ5 DANs and they cluster onto distinct dendritic branches, presumably separating its established roles in aversive reinforcement and appetitive motivation [5, 6]. Tracing also identified neurons that provide broad input to γ5, β′2a, and γ1pedc DANs, suggesting that distributed DAN populations can be coordinately regulated. These connectomic and behavioral analyses therefore reveal further complexity of dopaminergic reinforcement circuits between and within MB compartments., Highlights • Nanoscale anatomy reveals additional subtypes of rewarding dopaminergic neurons • Connectomics reveals input specificity to subtypes of dopaminergic neurons • Axon morphology implies dopaminergic neurons provide subcompartment-level function • Unique dopaminergic subtypes serve aversive memory extinction and sugar learning, Otto et al. use electron microscope resolution connectomics to describe the structure and organization of neurons providing synaptic input to functionally discrete subtypes of dopaminergic neurons. The nanoscale anatomy reveals further anatomical and functional specialization of dopaminergic neurons, which is confirmed with behavioral experiments.

We report the rare case of a 69-year-old man who underwent resection of a mixed adenoneuroendocrine carcinoma (MANEC) of the distal bile duct and a carcinoma in situ in the perihilar bile duct. The patient was admitted to our hospital for obstructive jaundice. Imaging studies revealed a mass in the distal bile duct, and an abnormal epithelium was detected in the perihilar bile duct using peroral cholangioscopy. Bile cytology and transpapillary biopsy of the tumor revealed adenocarcinoma. We diagnosed this patient with distal cholangiocarcinoma with extensive intraepithelial progression toward the perihilar bile duct and performed a subtotal stomach-preserving pancreaticoduodenectomy and left hepatectomy. According to the histological examination of the resected specimens, we found a MANEC in the distal bile duct and a carcinoma in situ in the perihilar bile duct. Together, they were diagnosed as synchronous double primary cancers due to the lack of pathological transition between them.

In Table 1 and in Result and discussion section, C2875F should read C2876F.

Background: Oxidative posttranslational modifications (OPTM) impair the function of Sarcoplasmic/endoplasmic reticulum (SR) calcium (Ca2+) ATPase (SERCA) 2 and trigger cytosolic Ca2+ dysregulation. We investigated the extent of OPTM of SERCA2 in patients with non-ischemic cardiomyopathy (NICM). Methods and results: Endomyocardial biopsy (EMB) was obtained in 40 consecutive patients with NICM. Total expression and OPTM of SERCA2, including sulfonylation at cysteine-674 (S-SERCA2) and nitration at tyrosine-294/295 (N-SERCA2), were examined by immunohistochemical analysis. S-SERCA2 increased in the presence of late gadolinium enhancement on cardiac magnetic resonance imaging. S-SERCA2/SERCA2 and N-SERCA2/SERCA2 correlated with cardiac fibrosis evaluated by Masson’s trichrome staining of EMB. SERCA2 expression modestly increased in parallel with an upward trend in OPTM of SERCA2 with aging. This tendency became prominent only in patients aged >65 years. OPTM of SERCA2 positively correlated with brain natriuretic peptide (BNP) values only in patients aged ≤65 years. Composite major adverse cardiac events (MACE) increased more in the high OPTM group of younger patients; however, MACE-free survival was similar irrespective of the extent of OPTM in older patients. Conclusions: OPTM of SERCA2 correlate with myocardial fibrosis in NICM. In younger patients, OPTM of SERCA2 correlate with elevated BNP and increased composite MACE. Keywords: SERCA2, Oxidative posttranslational modification, Myocardial fibrosis, Non-ischemic cardiomyopathy

The journal of comparative neurology 529(4), 905 - 925 (2021). doi:10.1002/cne.24987, Sensory systems provide input to motor networks on the state of the body and environment. One such sensory system in insects is the campaniform sensilla (CS), which detect deformations of the exoskeleton arising from resisted movements or external perturbations. When physical strain is applied to the cuticle, CS external structures are compressed, leading to transduction in an internal sensory neuron. In Drosophila melanogaster, the distribution of CS on the exoskeleton has not been comprehensively described. To investigate CS number, location, spatial arrangement, and potential differences between individuals, we compared the front, middle, and hind legs of multiple flies using scanning electron microscopy. Additionally, we imaged the entire body surface to confirm known CS locations. On the legs, the number and relative arrangement of CS varied between individuals, and single CS of corresponding segments showed characteristic differences between legs. This knowledge is fundamental for studying the relevance of cuticular strain information within the complex neuromuscular networks controlling posture and movement. This comprehensive account of all D. melanogaster CS helps set the stage for experimental investigations into their responsivity, sensitivity, and roles in sensory acquisition and motor control in a light-weight model organism., Published by Wiley-Liss, New York, NY [u.a.]

GN-z11 was photometrically selected as a luminous star-forming galaxy candidate at redshift z > 10 based on Hubble Space Telescope (HST) imaging data. Follow-up HST near-infrared grism observations detected a continuum break that was explained as the Ly-alpha break corresponding to z = 11.09 (+0.08-0.12). However, its accurate redshift remained unclear. Here we report a probable detection of three ultraviolet (UV) emission lines from GN-z11, which can be interpreted as the [C III] 1907, C III] 1909 doublet and O III] 1666 at z = 10.957+/-0.001 (when the Universe was only ~420 Myr old, or ~3% of its current age). This is consistent with the redshift of the previous grism observations, supporting GN-z11 as the most distant galaxy known to date. Its UV lines likely originate from dense ionized gas that is rarely seen at low redshifts, and its strong [C III] and C III] emission is partly due to an active galactic nucleus (AGN) or enhanced carbon abundance. GN-z11 is luminous and young, yet moderately massive, implying a rapid build-up of stellar mass in the past. Future facilities will be able to find the progenitors of such galaxies at higher redshift and probe the cosmic epoch in the beginning of re-ionization., Published in Nature Astronomy on Dec 14, 2020; 21 pages; authors' version

We report the rest-frame ultraviolet luminosity function of $g$-dropout galaxies in 177 protocluster candidates (PC UVLF) at $z\sim4$ selected in the Hyper Suprime-Cam Subaru Strategic Program. Comparing with the UVLF of field galaxies at the same redshift, we find that the PC UVLF shows a significant excess towards the bright-end. This excess can not be explained by the contribution of only active galactic nuclei, and we also find that this is more significant in higher dense regions. Assuming that all protocluster members are located on the star formation main sequence, the PC UVLF can be converted into a stellar mass function. Consequently, our protocluster members are inferred to have a 2.8 times more massive characteristic stellar mass than that of the field Lyman break galaxies at the same redshift. This study, for the first time, clearly shows that the enhancement in star formation or stellar mass in overdense regions can generally be seen as early as at $z\sim4$. We also estimate the star formation rate density (SFRD) in protocluster regions as $\simeq 6-20\%$ of the cosmic SFRD, based on the measured PC UVLF after correcting for the selection incompleteness in our protocluster sample. This high value suggests that protoclusters make a non-negligible contribution to the cosmic SFRD at $z\sim4$, as previously suggested by simulations. Our results suggest that protoclusters are essential components for the galaxy evolution at $z\sim4$., Comment: 22 pages, 16 figures, Accepted for publication in ApJ

Aims/Introduction Flash and continuous glucose monitoring systems are becoming prevalent in clinical practice. We directly compared a flash glucose monitoring system (FreeStyle Libre Pro [FSL‐Pro]) with a continuous glucose monitoring system (iPro2) in patients with diabetes mellitus. Materials and Methods Glucose concentrations were simultaneously measured using the FSL‐Pro, iPro2 and self‐monitoring blood glucose in 10 patients with diabetes mellitus, and agreement among them was assessed. Results Parkes error grid analysis showed that the 92.9 and 7.1% of glucose values measured using the FSL‐Pro fell into areas A and B, respectively, and that 96.3, 2.8 and 0.9% of those determined using iPro2 fell into areas A, B and C, respectively. The median absolute relative differences compared with self‐monitoring blood glucose were 8.1% (3.9–12.7%) and 5.0% (2.6–9.1%) for the FSL‐Pro and iPro2, respectively. Analysis of 5,555 paired values showed a close correlation between FSL‐Pro and iPro2 glucose values (ρ = 0.96, P

Background and study aims A newly developed peroral cholangioscopy (POCS) system, SpyGlassDS has high maneuverability. This study aimed to evaluate acceptability of the accuracy of SpyGlassDS accompanied by simultaneous POCS-guided biopsy compared with that of a traditional POCS scope, CHF-B260, to diagnose the lateral extent of extrahepatic cholangiocarcinoma (LEC). Patients and methods Patients who underwent surgical resection after preoperative examinations to diagnose LEC were evaluated. POCS by CHF-B260 was performed if there was discrepancy between preceding fluoroscopy-guided biopsy findings and other examinations between January 2004 and September 2015 (group A, n = 56); and POCS plus POCS-guided mapping biopsy by SpyGlassDS was performed in all surgical candidates between October 2015 and December 2017 (group B, n = 20). The main outcome measure was the accuracy of overall preoperative diagnosis (OPD) of LEC defined based on all examinations, including POCS. Results Accuracy of OPD for the liver side and the ampullary side was 93 % and 100 %, respectively, in group A, and 84 % and 100 %, respectively, in group B (P = 0.37 for the liver side; P, not available for the ampullary side). Diagnostic accuracy of simple optical evaluation by POCS for the liver side and the ampullary side was 83 % and 100 %, respectively, in group A, and 58 % and 88 %, respectively, in group B (P = 0.29 for the liver side; P = 0.40 for the ampullary side). Conclusions POCS by SpyGlassDS was found to be acceptable and could be a standard approach for diagnosis of LEC.

Stereotactic body radiotherapy (SBRT) is expected to achieve safe and effective re-irradiation for painful bone metastases. This study aimed to clarify the efficacy of re-irradiation using SBRT for painful bone metastases.Prospective database at our institution for the period between September 2013 and December 2017 were retrospectively reviewed for patients with: (1) painful bone metastases; (2) history of radiotherapy to the metastasis; and (3) SBRT performed as re-irradiation. Pain response, pain failure-free duration, analgesics medications, and adverse events were evaluated. Pain was evaluated using the Numerical Rating Pain Score, and pain response was evaluated based on International Consensus Pain Response Endpoints. Best response during follow-up was noted. Patients with complete or partial response were defined as showing pain response, and patients with pain progression were defined as showing pain failure. Adverse events were evaluated based on the RTOG/EORTC Late Radiation Morbidity Scoring Schema.Sixty-six patients selected from our database showed: median age, 65 years (range, 33-82 years); ECOG performance status, 0-1/2/3/4, 51/10/3/2; lesion histopathology, rectal/lung/renal/thyroid/other cancer, 13/11/9/5/28; median previous irradiated dose, 30 Gy (range, 8-70.4 Gy); median interval from latest irradiation, 21 months (range, 4-192 months); prescribed dose for SBRT, 24 Gy in 2 fractions/30 Gy in 5 fractions/35 Gy in 5 fractions, 51/13/2. Median follow-up after SBRT was 10 months (range, 1-37 months). Fifty-seven patients achieved pain response (86%). The 1-year pain failure-free rate was 55%. Median pain failure-free duration was 13 months (range, 1-24 months). Grade 4 adverse events were observed in six patients (vertebral compression fracture, n = 5; radiation myelopathy, n = 1). No other toxicities of Grade 3 or greater were encountered.Re-irradiation SBRT has potential to achieve good response and long-term pain control for painful bone metastases. Prospective analysis is necessary to confirm the safety and efficacy of SBRT as re-irradiation.

OBJECTIVEThis study aimed to clarify the outcomes of postoperative re-irradiation using stereotactic body radiotherapy (SBRT) for metastatic epidural spinal cord compression (MESCC) in the authors’ institution and to identify factors correlated with local control.METHODSCases in which patients with previously irradiated MESCC underwent decompression surgery followed by spine SBRT as re-irradiation between April 2013 and May 2017 were retrospectively reviewed. The surgical procedures were mainly performed by the posterior approach and included decompression and fixation. The prescribed dose for spine SBRT was 24 Gy in 2 fractions. The primary outcome was local control, which was defined as elimination, shrinkage, or no change of the tumor on CT or MRI obtained approximately every 3 months after SBRT. In addition, various patient-, treatment-, and tumor-specific factors were evaluated to determine their predictive value for local control.RESULTSTwenty-eight cases were identified in the authors’ institutional databases as meeting the inclusion criteria. The histology of the primary disease was thyroid cancer in 7 cases, lung cancer in 6, renal cancer in 3, colorectal cancer in 3, and other cancers in 9. The most common previous radiation dose was 30 Gy in 10 fractions (15 cases). The mean interval since the most recent irradiation was 16 months (range 5–132 months). The median duration of follow-up after SBRT was 13 months (range 4–38 months). The 1-year local control rate was 70%. In the analysis of factors related to local control, Bilsky grade, number of vertebral levels in the treatment target, the interval between the latest radiotherapy and SBRT, recursive partitioning analysis (RPA), the prognostic index for spinal metastases (PRISM), and the revised Tokuhashi score were not significantly correlated with local control. The favorable group classified by the Rades prognostic score achieved a significantly higher 1-year local control rate than the unfavorable group (1-year local control rate: 100% vs 33%; p < 0.01). Radiation-induced myelopathy and vertebral compression fracture were observed in 1 and 3 patients, respectively. No other grade 3 or greater toxicities were encountered.CONCLUSIONSThe results indicate that spine SBRT as postoperative re-irradiation was effective, and it was especially useful for patients classified as having a good survival prognosis according to the Rades score.

We perform a stacking analysis of {\it Planck}, {\it AKARI}, Infrared Astronomical Satellite ($IRAS$), Wide-field Infrared Survey Eplorer ($WISE$), and {\it Herschel} images of the largest number of (candidate) protoclusters at $z\sim3.8$ selected from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP). Stacking the images of the $179$ candidate protoclusters, the combined infrared (IR) emission of the protocluster galaxies in the observed $12-850~\mu$m wavelength range is successfully detected with $>5\sigma$ significance (at $Planck$). This is the first time that the average IR spectral energy distribution (SED) of a protocluster has been constrained at $z\sim4$. The observed IR SEDs of the protoclusters exhibit significant excess emission in the mid-IR compared to that expected from typical star-forming galaxies (SFGs). They are reproduced well using SED models of intense starburst galaxies with warm/hot dust heated by young stars, or by a population of active galactic nuclei (AGN)/SFG composites. For the pure star-forming model, a total IR (from 8 to 1000 $\mu$m) luminosity of $19.3_{-4.2}^{+0.6}\times10^{13}~L_{\odot}$ and a star formation rate (SFR) of $16.3_{-7.8}^{+1.0}\times10^3~M_{\odot}$ yr$^{-1}$ are found whereas for the AGN/SFG composite model, $5.1_{-2.5}^{+2.5}\times10^{13}~L_{\odot}$ and $2.1^{+6.3}_{-1.7}\times10^3~M_{\odot}$ yr$^{-1}$ are found. Uncertainty remaining in the total SFRs; however, the IR luminosities of the most massive protoclusters are likely to continue increasing up to $z\sim4$. Meanwhile, no significant IR flux excess is observed around optically selected QSOs at similar redshifts, which confirms previous results. Our results suggest that the $z\sim4$ protoclusters trace dense, intensely star-forming environments that may also host obscured AGNs missed by the selection in the optical., Comment: 26 pages, 12 figures, Accepted for publication in ApJ

The insect central complex and vertebrate basal ganglia are forebrain centres involved in selection and maintenance of behavioural actions. However, little is known about the formation of the underlying circuits, or how they integrate sensory information for motor actions. Here, we show that paired embryonic neuroblasts generate central complex ring neurons that mediate sensory-motor transformation and action selection in Drosophila. Lineage analysis resolves four ring neuron subtypes, R1-R4, that form GABAergic inhibition circuitry among inhibitory sister cells. Genetic manipulations, together with functional imaging, demonstrate subtype-specific R neurons mediate the selection and maintenance of behavioural activity. A computational model substantiates genetic and behavioural observations suggesting that R neuron circuitry functions as salience detector using competitive inhibition to amplify, maintain or switch between activity states. The resultant gating mechanism translates facilitation, inhibition and disinhibition of behavioural activity as R neuron functions into selection of motor actions and their organisation into action sequences.

Objective Endoscopic papillary large-balloon dilation (EPLBD) for common bile duct (CBD) stone removal has been confirmed to be safe and effective in the short term. The long-term outcomes of EPLBD, which have not been sufficiently evaluated, were therefore investigated in this study. Methods For patients who had undergone endoscopic CBD stone removal with EPLBD between October 2011 and December 2015, follow-up surveys were conducted using a postal survey, telephone interview, or medical record review in August 2017. The main outcome measurement was the recurrence rate of CBD stones after complete stone removal with EPLBD in patients who received follow-up for more than one year. Risk factors for such recurrence were secondarily analyzed. Results Of the 98 patients treated using EPLBD, 93 (95%) were followed up after complete stone removal and analyzed for the long-term outcomes. During the mean follow-up period of 33.7±16.6 months, CBD stones recurred in 16 patients (17%) with a mean interval of 12.7±12.7 months. Univariate analyses showed that a large stone size, multiple stones, a large distal CBD diameter, and a history of cholecystectomy were significant risk factors for stone recurrence (p=0.022, 0.013, 0.001 and 0.035, respectively). The large distal CBD diameter was the only significant risk factor for stone recurrence in a multivariate analysis (hazard ratio, 1.227; p=0.031). Conclusion The long-term outcomes of EPLBD for CBD stones, including the rate of stone recurrence, were found to be acceptable. A large distal CBD diameter was an independent risk factor for stone recurrence.

We have carried out follow-up spectroscopy on three overdense regions of $g$- and $r$-dropout galaxies in the Canada-France-Hawaii Telescope Legacy Survey Deep Fields, finding two new protoclusters at $z=4.898$, 3.721 and a possible protocluster at $z=3.834$. The $z=3.721$ protocluster overlaps with a previously identified protocluster at $z=3.675$. The redshift separation between these two protoclusters is $\Delta z=0.05$, which is slightly larger than the size of typical protoclusters. Therefore, if they are not the progenitors of a $>10^{15}\,\mathrm{M_\odot}$ halo, they would grow into closely-located independent halos like a supercluster. The other protocluster at $z=4.898$ is also surrounded by smaller galaxy groups. These systems including protoclusters and neighboring groups are regarded as the early phase of superclusters. We quantify the spatial distribution of member galaxies of the protoclusters at $z=3.675$ and 3.721 by fitting triaxial ellipsoids, finding a tentative difference: one has a pancake-like shape while the other is filamentary. This could indicate that these two protoclusters are in different stages of formation. We investigate the relation between redshift and the velocity dispersion of protoclusters, including other protoclusters from the literature, in order to compare their dynamical states. Although there is no significant systematic trend in the velocity dispersions of protoclusters with redshift, the distribution is skewed to higher velocity dispersion over the redshift range of $z=2\mathrm{-}6$. This could be interpreted as two phases of cluster formation, one dominated by the steady accretion of galaxies, and the other by the merging between group-size halos, perhaps depending on the surrounding large-scale environments., Comment: Accepted for publication in ApJ, 24 pages, 12 figures, 5 tables

Two-phase flow through porous media must be well understood to develop a severe accident analysis code not only for light water reactor but also sodium-cooled fast reactor. When a core disruptive accident occurs in sodium-cooled fast reactor, the fuel inside the core become melted and interacts with the coolant. As a result, gas-liquid two-phase flow will be formed in the debris bed, which may have porous nature depending on the cooling process. In such condition, the local porosity and its distribution are very important to characterize two-phase flow field in the porous media. In this study, X-ray radiography was applied to measure the local porosity in the packed bed of spheres. The radial profiles were estimated from the chordal profiles measured by the X-ray method and compared with the previous porosity model. In addition, the void fraction radial profiles were also obtained in air-water two-phase flow.

Purulent pericarditis is a rare disease in the antibiotic era. The common pathogens of purulent pericarditis are gram-positive species such as Staphylococcus aureus. Streptococcus pneumoniae, Salmonella, Haemophilus, fungal pathogens/tuberculosis can also result in purulent pericarditis. We report an old male case of purulent pericarditis by Escherichia coli. He came to our hospital suffering from leg edema for 3 months. Echocardiography revealed the large amount of pericardial effusion, and he was admitted to test the cause of pericardial effusion without high fever, tachycardia, and shock vital signs. On the third day, he suddenly presented vital shock. We performed emergency cardiopulmonary resuscitation and pericardiocentesis. Appearance of pericardial effusion was hemorrhagic and purulent. The gram stain revealed remarkable E. coli invasion to pericardial space. Antibiotic therapy was immediately started; however, he died on sixth day with septic shock. The cytological examination of pericardial effusion suggested the invasion of malignant lymphoma to pericardium. This case showed subacute or chronic process of pericarditis without severe clinical and laboratory sings before admission. Nevertheless, bacterial purulent pericarditis usually shows acute clinical manifestation; the first process of this case was very silent. Immunosuppression of malignant lymphoma might make E. coli translocation from gastrointestinal tract to pericardial space, and bacterial pericarditis was progressed to purulent pericarditis. In the latter process, this case showed unexpected rush progression to death by sepsis from purulent pericarditis. Immediate pericardiocentesis should be performed for a prompt diagnosis of purulent pericarditis, and it might have improved the outcome of this case.

Background/aims Although both radial- and convex-arrayed endoscopic ultrasonography (EUS) scopes are widely used for observational EUS examinations, there have been few comparative studies on their power of visualization. The aim of this study was to evaluate the capability of these EUS scopes for observation of the pancreatobiliary junction. Methods The rate of successful visualization of the pancreatobiliary junction was retrospectively compared between a radial-arrayed and a convex-arrayed echoendoscope, from a prospectively maintained database. Study periods were defined as January 2010 to December 2012 for the radial group, and February 2015 to October 2016 for the convex group because the respective scope was mainly used during those periods. Results During the study period, 1,660 cases with radial EUS and 1,984 cases with convex EUS were recruited. The success rates of observation of the pancreatobiliary junction were 80.0% and 89.5%, respectively (pl0.0001). Conclusions The capability of visualization of the pancreatobiliary junction in observational EUS was found to be better with a convex-arrayed than with a radial-arrayed echoendoscope.

The liver is one of the most common sites of metastasis [1], and liver metastases (LM) often cause symptoms such as pain, discomfort and nausea [2,3]. Some prospective clinical trials have demonstr...

We herein report the case of a 74-year-old man who underwent surgery 9 years after his initial visit and who was pathologically diagnosed with signet-ring cell carcinoma (SRCC) derived from a main-duct-type intraductal papillary mucinous neoplasm (MD-IPMN). At the first imaging examination, only a small pancreatic cyst with mild dilation of the main pancreatic duct (MPD) was detected in the pancreatic head. Eventually, MD-IPMN with mural nodules and MPD dilation (30 mm) developed in the pancreatic body, while the pancreatic head cyst remained unchanged. Total pancreatectomy was performed and the MD-IPMN was pathologically diagnosed as SRCC derived from an intestinal-type MD-IPMN.