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Bioplastics have garnered substantial interest as alternatives to conventional petroleum-based plastics. However, their management and conversion to biogas continues to be significantly challenging. In this study, we evaluated the suitability of various plastics for hydrolysis at 160 °C for 12 h using different solvents. The biogas yield (BGY) of the monomers constituting these plastics and the obtained plastic hydrolyzates was comprehensively evaluated. When water was used as a solvent, 100 % hydrolysis of polylactic acid (PLA) and polybutylene succinate (PBS) was observed. When polybutylene adipate co-terephthalate (PBAT) and polyhydroxybutyrate (PHB) were hydrolyzed with water, the degradation ratio was approximately 30 %; however, using an aqueous lactic acid solution as a solvent improved the degradation ratio to 78 % and 100 %, respectively. In the BGY test of the plastic hydrolyzates, the biogas volumes derived from the hydrolyzates were 563, 461, 337, and 573 mL/g COD-added for PLA, PBS, PBAT, and PHB, respectively. With 1,160 gCOD/L waste PLA hydrolyzate, continuous co-digestion of sewage sludge and the hydrolyzate was conducted. Organic loading rates of sewage sludge and the hydrolyzate were 2.3 and 2.4 gCOD/L/d, respectively. The operation was stable and the methane production volume from the PLA hydrolyzate was 414 L/kgCOD-added. Using highly concentrated PLA hydrolyzate, the hydraulic retention time was 19.3 days, which was only 0.7 days shorter than that of anaerobic digestion of sewage sludge only (20 days). Therefore, highly concentrated PLA hydrolyzate maintains the retention time of normal sewage sludge digestion. Conclusively, the present study has crucial practical implications for plastic waste management.

Abstract Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

Protected Areas (PAs) in Bangladesh have been pivotal for conserving wildlife. The country plans to increase the number of PAs by implementing new forest-governing policies with the involvement of local communities. Their efficacy in wildlife conservation and forest preservation is being questioned due to significant land cover changes within PA boundaries. It is essential to understand the current role of existing PAs in forest cover transformation and their impact on wildlife conservation before expanding the PAs and implementing new policies. This study aims to explore the land cover transformation within Teknaf Wildlife Sanctuary (TWS) and describe the role of the local community and its impact on wildlife. Utilizing Landsat satellite images from 1989 to 2015, this study discovered a 46 % deforestation rate within TWS, surpassing its surrounding areas. Since 1989, 75 % of primary forests have been eradicated, leaving a mere 650 hectares intact. This transformation is shifting forested areas towards the PA boundaries, potentially threatening conservation efforts by making wildlife more vulnerable. Socioeconomic surveys of 5769 households revealed that bigger landowners within the local communities played a significant role in this deforestation. Such community-driven forest alterations increased wildlife vulnerability by intensifying their interaction with forest surrounding communities. This study presents an interesting case of the process of forest transformation within PAs with the intersection of human-wildlife conflict and deforestation. For effective wildlife conservation, strategies need to address and rectify these forest cover transformations and focus on the wildlife habitats, ensuring conservation and coexistence for forests, humans and wildlife.

Abstract Periplasmic solute-binding proteins (SBPs) specific for chitooligosaccharides, (GlcNAc)n (n = 2, 3, 4, 5 and 6), are involved in the uptake of chitinous nutrients and the negative control of chitin signal transduction in Vibrios. Most translocation processes by SBPs across the inner membrane have been explained thus far by two-domain open/closed mechanism. Here we propose three-domain mechanism of the (GlcNAc)n translocation based on experiments using a recombinant VcCBP, SBP specific for (GlcNAc)n from Vibrio cholerae. X-ray crystal structures of unliganded or (GlcNAc)3-liganded VcCBP solved at 1.2–1.6 Å revealed three distinct domains, the Upper1, Upper2 and Lower domains for this protein. Molecular dynamics simulation indicated that the motions of the three domains are independent and that in the (GlcNAc)3-liganded state the Upper2/Lower interface fluctuated more intensively, compared to the Upper1/Lower interface. The Upper1/Lower interface bound two GlcNAc residues tightly, while the Upper2/Lower interface appeared to loosen and release the bound sugar molecule. The three-domain mechanism proposed here was fully supported by binding data obtained by thermal unfolding experiments and ITC, and may be applicable to other translocation systems involving SBPs belonging to the same cluster.

PurposeIn patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals.MethodsSWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan.ResultsThe primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events.ConclusionsThe SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems.

Objective structured clinical examinations (OSCEs) are a widely used performance assessment for medical and dental students. A common limitation of OSCEs is that the evaluation results depend on the characteristics of raters and a scoring rubric. To overcome this limitation, item response theory (IRT) models such as the many-facet Rasch model have been proposed to estimate examinee abilities while taking into account the characteristics of raters and evaluation items in a rubric. However, conventional IRT models have two impractical assumptions: constant rater severity across all evaluation items in a rubric and an equal interval rating scale among evaluation items, which can decrease model fitting and ability measurement accuracy. To resolve this problem, we propose a new IRT model that introduces two parameters: (1) a rater-item interaction parameter representing the rater severity for each evaluation item and (2) an item-specific step-difficulty parameter representing the difference in rating scales among evaluation items. We demonstrate the effectiveness of the proposed model by applying it to actual data collected from a medical interview test conducted at Tokyo Medical and Dental University as part of a post-clinical clerkship OSCE. The experimental results showed that the proposed model was well-fitted to our OSCE data and measured ability accurately. Furthermore, it provided abundant information on rater and item characteristics that conventional models cannot, helping us to better understand rater and item properties.

Background/aimAntiviral hepatitis and systemic therapies for hepatocellular carcinoma (HCC) remarkably progressed in the recent 10 years. This study aimed to reveal the actual transition and changes in the prognosis and background liver disease in non-advanced HCC in the past 20 years.MethodsThis retrospectively recruited 566 patients who were diagnosed with non-advanced HCC from February 2002 to February 2022. The prognosis was analyzed by subdividing according to the diagnosis date (period I: February 2002-April 2009 and period Ⅱ: May 2009-February 2022).ResultsPatients in period II (n = 351) were significantly older, with lower albumin-bilirubin (ALBI) scores and alpha-fetoprotein (AFP) and more anti-viral therapy, systemic therapy, and hepatic arterial infusion chemotherapy as compared with those in period I (n = 215). The etiology ratio of the background liver disease revealed decreased hepatitis C virus from 70.6% to 49.0% and increased non-B, non-C from 17.7% to 39.9% from periods I to Ⅱ. The multivariate analysis revealed older age and higher ALBI score in Barcelona Clinic Liver Cancer (BCLC) 0/A stage, AFP of >20 ng/mL, and higher ALBI score in BCLC B stage as independent prognosis factors. Fine-Gray competing risk model analysis revealed that liver-related deaths significantly decreased in period II as compared to period I, especially for BCLC stage 0/A (HR: 0.656; 95%CI: 0.442-0.972, P = 0.036).ConclusionThe characteristics of patients with non-advanced HCC have changed over time. Appropriate background liver management led to better liver-related prognoses in BCLC 0/A.

Integrating power-to-gas system with anaerobic digestion is an innovative approach towards sustainable energy generation where biogas production is enhanced through the addition of clean hydrogen. However, concerns regarding its stable performance and inhibition control remain particularly in thermophilic conditions. The objective of this research is therefore to develop a feasible and energy-efficient operation of biomethanation by assessing the hydrogen dissolution rate and biogas productivity in a thermophilic anaerobic digestion system. Two digesters (2 L) were fed with sewage sludge and operated simultaneously under 55.0 ± 0.1°C. Results revealed low equilibrium hydrogen gas concentration (< 1%) in the biogas implying an effective hydrogen gas-to-liquid mass transfer at a hydrogen injection rate of 0.54 NL L-reactor∁E d∁E. At this loading rate, high methane concentration (81 ± 1%) was observed with biogas yield up to 0.67 NL g-(volatile solids added)∁E. However, a sudden increase in loading resulted in a significant decrease in biogas production where possible inhibition due to high pH and volatile fatty acids accumulation had occurred. The findings from this study provide fundamental information to understand the underlying mechanism and performance of exogenous hydrogen addition in the digestion process.

Abstract Over the past few decades, hydrous minerals were thought to be absent in the lower mantle, due to their instability at high-pressure conditions. Recently, however, hydrous phases including phase H (MgSiO $$_4$$ 4 H $$_2$$ 2 ), pyrite-type FeOOH, and $$\delta$$ δ -AlOOH have been discovered to be thermodynamically stable at lower mantle pressures. Investigations using ab initio calculations methods play a key role in identifying these novel phases and determining their geophysical properties (i.e., compressibility, elasticity, and sound velocities). These calculations suggest that the hydrous minerals which are stable at lower mantle pressure conditions (i.e., phase H, FeOOH, and AlOOH), have symmetric hydrogen bonds at these pressures. This indicates that hydrogen bond strength is closely connected to the stability and physical properties of hydrous minerals at extreme pressures. In this review, we summarize the theoretical and experimental studies of hydrous minerals stable at the high-pressure conditions of the Earth’s lower mantle in light of the role of hydrogen bonding.

Zhou and Si et al. used cryogenic electron microscopy and tomography to delineate the molecular interactions among genomic RNA, nucleocapsid protein, matrix protein and glycoprotein in vesicular stomatitis virus and suggest a model of assembly.

A 78-year-old man developed paresthesias in the extremities. He was referred to our hospital because of positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies in the serum and the presence of abnormal lymphocytes. He was diagnosed as chronic-type adult T-cell leukemia/lymphoma. Neurological examination revealed sensory impairment in the distal parts of the extremities with loss of deep tendon reflexes. Nerve conduction study showed motor and sensory demyelinating polyneuropathy, indicating a diagnosis of HTLV-1-associated demyelinating neuropathy. Corticosteroid therapy followed by intravenous immunoglobulin therapy improved his symptoms. Since demyelinating neuropathy associated with HTLV-1 infection is not well recognized, we here report its characteristics and clinical course through our case report and literature review.

Galactosialidosis (GS) is a lysosomal cathepsin A (CTSA) deficiency. It associates with a simultaneous decrease of neuraminidase 1 (NEU1) activity and sialylglycan storage. Central nervous system (CNS) symptoms reduce the quality of life of juvenile/adult-type GS patients, but there is no effective therapy. Here, we established a novel GS model mouse carrying homozygotic Ctsa IVS6+1g→a mutation causing partial exon 6 skipping with concomitant deficiency of Ctsa/Neu1. The GS mice developed juvenile/adult GS-like symptoms, such as gargoyle-like face, edema, proctoprosia due to sialylglycan accumulation, and neurovisceral inflammation, including activated microglia/macrophage appearance and increase of inflammatory chemokines. We produced human CTSA precursor proteins (proCTSA), a homodimer carrying terminal mannose 6-phosphate (M6P)-type N-glycans. The CHO-derived proCTSA was taken up by GS patient-derived fibroblasts via M6P receptors and delivered to lysosomes. Catalytically active mature CTSA showed a shorter half-life due to intralysosomal proteolytic degradation. Following single i.c.v. administration, proCTSA was widely distributed, restored the Neu1 activity, and reduced the sialylglycans accumulated in brain regions. Moreover, proCTSA suppressed neuroinflammation associated with reduction of activated microglia/macrophage and up-regulated Mip1α. The results show therapeutic effects of intracerebrospinal enzyme replacement utilizing CHO-derived proCTSA and suggest suppression of CNS symptoms.

Background/purpose: The haptic 3D virtual reality dental training simulator has been drawn attention as a educational strategy in Covid-19 pandemic. The purpose of this study is to investigate the feature of the haptics simulator in comparison with a conventional mannequin simulator by analyzing the assessment of products prepared by dental students using these two kinds of simulator. Materials and methods: The subjects were 30 students in the sixth-year classes of the faculty of dentistry. Abutments for a full cast crown were prepared by each subject using two kinds of simulator; one is the haptics simulator and the other is a mannequin simulator. For the resulted products, occlusal surface form, margin design, surface smoothness, taper angle, total cut volume and overall impression were rated by 3 evaluators. Score differences between two simulators were statistically analyzed. Results: The kinds of simulator affected subject performance for margin design and total cut volume. The differences in cutting feeling between the simulators as well as variation of stereoscopic ability in subjects were considerable reasons. Evaluators’ rating was affected by difference in simulators for occlusal surface form, total cut volume, and overall impression. This may have been due to variation of stereoscopic ability in evaluators. Conclusion: The unique characteristics of virtual reality, such as the simulated cutting sensation and the simulated three-dimensional images created by stereo viewers, affect operators’ performance and evaluators’ rating. It was suggested that educational programs need to be constructed taking account of the characteristics of virtual reality to make the best use of the haptics simulator.

Abstract Background Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense. Case presentation A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat. Mycobacterial tissue culture and polymerase chain reaction testing revealed the presence of Mycobacterium abscessus subspecies massiliense in the nasopharyngeal tissue. This patient underwent surgery, followed by multiple rounds of chemotherapy with oral and intravenous antibiotic agents for 16 weeks. She has had no recurrence during the 56 weeks since treatment. Conclusion It is difficult to detect the presence of Mycobacterium abscessus subspecies massiliense in a culture from the swabbing sample. The tissue culture from a biopsy specimen is mandatory for the identification of the species. Currently, no definite treatment policy is available and only empirical treatment is applied. This case is an important for the diagnosis and treatment of this bacterial infection on nasopharynx.

Abstract We propose a way to observe the photon ring of the asymptotically anti-de Sitter black hole dual to a superconductor on the two-dimensional sphere. We consider the electric current of the superconductor under the localized time-periodic external electromagnetic field. On the gravity side, the bulk Maxwell field is sent from the AdS boundary and then diffracted by the black hole. We construct the image of the black hole from the asymptotic data of the bulk Maxwell field that corresponds to the electric current on the field theory side. We decompose the electric current into the dissipative and non-dissipative parts and take the dissipative part for the imaging of the black hole. We investigate the effect of the charged scalar condensate on the image. We obtain the bulk images that indicate the discontinuous change of the size of the photon ring.

Abstract Aim This study aimed to assess the response of endogenous beta‐hydroxybutyrate to psychological stress, and its association with nucleotide‐binding domain, leucine‐rich repeat, pyrin domain‐containing 3 (NLRP3) inflammasome, and stress‐induced behavior. Methods Male C57BL/6J mice were subjected to 1‐hour restraint stress to examine changes in the endogenous beta‐hydroxybutyrate and active NLRP3 levels in the prefrontal cortex. Subsequently, we created a depression model applying 10‐day social defeat stress to the male C57BL/6J mice. Results One‐hour restraint stress rapidly increased beta‐hydroxybutyrate levels in the blood. The active NLRP3 levels in the prefrontal cortex also increased significantly. A correlation was found between the increased beta‐hydroxybutyrate levels in the blood and the active NLRP3 levels in the prefrontal cortex. The mice exposed to social defeat stress exhibited depression‐ and anxiety‐like behavioral changes in the open field, social interaction, and forced swim tests. There was a correlation between these behavioral changes and endogenous beta‐hydroxybutyrate levels. Among the social defeat model mice, those with high beta‐hydroxybutyrate levels tended to have more depression‐ and anxiety‐like behavior. Conclusions The increased blood beta‐hydroxybutyrate levels due to psychological stress correlate with the active NLRP3 levels in the prefrontal cortex, suggesting that the increased beta‐hydroxybutyrate levels due to stress may reflect a reaction to brain inflammation. In addition, mice with higher blood beta‐hydroxybutyrate levels tend to exhibit increased depression‐ and anxiety‐like behaviors; thus, an increase in blood beta‐hydroxybutyrate levels due to stress may indicate stress vulnerability.

A 66-year-old woman with a history of bronchial asthma had shortness of breath and fatigue upon mild exercise. She was diagnosed as congestive heart failure. A blood test showed eosinophilia without the presence of anti-neutrophil cytoplasmic antibody (ANCA), and a myocardial biopsy specimen revealed eosinophilic infiltration in the myocardium. Eosinophilia was improved when she was administered short-term methylprednisolone. After that, she had numbness and pain in her lower limbs with re-elevation of eosinophils. She had dysesthesia and hypalgesia in the distal part of the limbs. Sural nerve biopsy revealed axonal degeneration and thickness of the arterial wall, indicating a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA). Two courses of steroid pulse therapy were performed, resulting in marked improvement of her sensory symptoms. ANCA-negative EGPA might be associated with myocarditis and peripheral neuropathy. A sufficient immunotherapy should have been considered to prevent rapid progression.

Gastric mixed adenocarcinoma-neuroendocrine tumor (NET) is a rare composite tumor, and a limited number of studies have reported on it. A 77-year-old man was admitted to our hospital because of acute cholecystitis. He underwent a cholecystectomy. Esophagogastroduodenoscopy during his admission revealed a slightly elevated tumor, and biopsy demonstrated a well-differentiated tubular adenocarcinoma. The tumor was resected completely by endoscopic submucosal dissection. Histological findings showed that it measured 9 mm in diameter, was located within the mucosa, and consisted of well-differentiated tubular adenocarcinoma and a NET G1. The NET was covered with adenocarcinoma and both components exhibited histological continuity. The NET and a part of the adenocarcinoma component showed a positive reaction for chromogranin A and synaptophysin. Neither enterochromaffin-like cell hyperplasia nor endocrine cell micronest surrounded the tumor. The diagnosis was gastric mixed adenocarcinoma-NET. The histological continuity between the two components can be likened to the same histogenesis.

Bangladesh is experiencing deforestation within its protected forest areas (PAs). One reason for its inability to stem deforestation is the lack of a proper understanding of the deforestation process and the drivers responsible for it. This study aims to elucidate the socioeconomic factors influencing deforestation within a PA on the coast of Bangladesh known as Teknaf Wildlife Sanctuary (TWS). In the quest to understand the drivers of deforestation, the extent of community involvement in the deforestation process was explored. The local community was grouped based on their involvement in various deforestation drivers. These groups were then compared to determine the socioeconomic factors influencing the likelihood of their involvement in deforestation. The community survey covered 10% of households in the community surrounding TWS and involved interviewing 5769 household heads. This study found that 2150 households (37% of all surveyed households) were engaged in fuelwood collection, 623 (11%) were encroaching on the TWS, and 506 (9%) were cultivating betel leaves. Therefore, 45% of households were engaged in some form of deforestation driver. Among the socioeconomic factors, new households with small properties had a higher likelihood of being involved in deforestation drivers. Moreover, comparatively poor households had a significantly higher probability of being engaged in deforestation. Regarding occupations, farmers and laborers had a higher likelihood of being associated with deforestation. This study sheds light on the complex interplay of socioeconomic factors influencing the deforestation process occurring within a specific PA in Bangladesh under existing forest policies. This understanding can be useful for policymakers and forest managers in developing effective forest policies and managing forests more sustainably.

A 31-year-old woman presented with a nasal voice, dysarthria, and upper limb weakness during her first pregnancy. Soon after delivery of her first baby, her symptoms disappeared. At the age of 34 years, during her second pregnancy, her nasal voice re-appeared. After delivery of the second baby, her nasal voice worsened, and bilateral eyelid ptosis and easy fatigability were also evident. She was referred to our hospital. Because of her myasthenic symptoms and anti-muscle-specific tyrosine kinase (MuSK) antibody (Ab)-positive status, she was diagnosed as having myasthenia gravis (MG). Her symptoms were worse than those in her first pregnancy. She was treated with oral steroid and double filtration plasmapheresis. After initiation of treatment, her myasthenic symptoms improved completely. In addition, her baby developed transient neonatal MG (TNMG) on the fourth day after birth and then gradually recovered over 30 days. It should be noted that symptoms of patients with anti-MuSK Ab-positive MG (MuSK-MG) can deteriorate during pregnancy, and the babies delivered of patients with MuSK-MG have a high probability of developing TNMG.

Formation of intrahepatic bile ducts (IHBDs) proceeds in accordance with their microenvironment. Particularly, mesenchymal cells around portal veins regulate the differentiation and ductular morphogenesis of cholangiocytes in the developing liver; however, further studies are needed to fully understand the arrangement of IHBDs into a continuous hierarchical network. This study aims to clarify the interaction between biliary and liver mesenchymal cells during IHBD formation. To identify candidate factors contributing to this cell–cell interaction, mesenchymal cells were isolated from embryonic day 16.5 matrix metalloproteinase 14 (MMP14)‐deficient (knockout [KO]) mice livers, in which IHBD formation is retarded, and compared with those of the wild type (WT). WT mesenchymal cells significantly facilitated the formation of luminal structures comprised of hepatoblast‐derived cholangiocytes (cholangiocytic cysts), whereas MMP14‐KO mesenchymal cells failed to promote cyst formation. Comprehensive analysis revealed that expression of vasoactive intestinal peptide (VIP) was significantly suppressed in MMP14‐KO mesenchymal cells. VIP and VIP receptor 1 (VIPR1) were mainly expressed in periportal mesenchymal cells and cholangiocytic progenitors during IHBD development, respectively, in vivo. VIP/VIPR1 signaling significantly encouraged cholangiocytic cyst formation and up‐regulated tight junction protein 1, cystic fibrosis transmembrane conductance regulator, and aquaporin 1, in vitro. VIP antagonist significantly suppressed the tight junction assembly and the up‐regulation of ion/water transporters during IHBD development in vivo. In a cholestatic injury model of adult mice, exogenous VIP administration promoted the restoration of damaged tight junctions in bile ducts and improved hyperbilirubinemia. Conclusion: VIP is produced by periportal mesenchymal cells during the perinatal stage. It supports bile duct development by establishing tight junctions and up‐regulating ion/water transporters in cholangiocytes. VIP contributes to prompt recovery from cholestatic damage through the establishment of tight junctions in the bile ducts.

We encountered a rare case of single anterior compartment syndrome (CS) in a 43-year-old male patient who underwent Achilles tendon repair (ATR). The ATR was completed without tourniquet use uneventfully, three days following an injury to the left Achilles tendon. Two days later, unexplainable pain in the left anterior lower leg and numbness of the ipsilateral dorsal foot developed, and the patient's condition gradually deteriorated. An isolated increase in pressure to over 190 mmHg was observed within the anterior compartment; therefore, we performed an emergency fasciotomy. However, the patient's left dorsal foot never regained complete sensation, and plantar flexion of his ankle and hallux remained impaired. In this case, the cause of CS was not clear. Few case reports have described CS following ATR. We understand from our experience the importance of being careful about CS even if we operate in posterior compartment only.

Background and objectiveA cytokine storm is caused by inflammatory cells, including pro-inflammatory macrophage phenotype (M1), and play a critical role in the pathogenesis of COVID-19, in which diffuse alveolar damage occurs in the lungs due to oxidative stress exposure. Heme oxygenase (HO)-1 is a stress-induced protein produced by the anti-inflammatory / anti-oxidative macrophage phenotype (M2), which also produces soluble CD163 (sCD163). In our study, we investigated and determined that serum HO-1 can be a predictive biomarker for assessing both the severity and the outcome of COVID-19 patients.MethodThe serum concentrations of HO-1 and sCD163 of COVID-19 patients were measured on admission. The relationship between these biomarkers and other clinical parameters and outcomes were evaluated.ResultsSixty-four COVID-19 patients (11 mild, 38 moderate, and 15 severe cases) were assessed. The serum HO-1 tended to increase (11.0 ng/mL vs. 24.3 ng/mL vs. 59.6 ng/mL with severity). Serum HO-1 correlated with serum lactate dehydrogenase (R = 0.422), C-reactive protein (R = 0.463), and the ground glass opacity (GGO) and consolidation score (R = 0.625) of chest computed tomography. The serum HO-1 showed a better area under the curve (AUC) for predicting ICU admission than the serum sCD163 (HO-1; 0.816 and sCD163; 0.743). In addition, composite parameters including serum HO-1 and the GGO and consolidation score showed a higher AUC for predicting ICU admission than the AUC of a single parameter.ConclusionClinically, serum HO-1, reflecting the activation of M2, could be a very useful marker for evaluating disease severity and predicting prognoses for COVID-19 patients. In addition, controlling activated M2 might be a preventative COVID-19 therapeutic target.

We describe an 83-year-old man who presented with acute ischemic stroke after an inguinal hernia operation. After mechanical thrombectomy, the patient regained full neurological function; however, 5 days later, he developed left hemichorea without radiological abnormalities at that time. His hemichorea was successfully treated with a small dose of haloperidol. A slight hyperintense signal was noted at the right putamen on T1-weighted imaging performed 43 days after the onset. This is the first report to highlight the development of delayed-onset hemichorea, despite the initial resolution of the neurological symptoms in a patient with acute ischemic stroke successfully treated with mechanical thrombectomy.

Entanglement entropy (EE) is a quantitative measure of the effective degrees of freedom and the correlation between the sub-systems of a physical system. Using the replica trick, we can obtain the EE by evaluating the entanglement Renyi entropy (ERE). The ERE is a q-analogue of the EE and expressed by the q replicated partition function. In the semi-classical approximation, it is apparently easy to calculate the EE because the classical action represents the partition function by the saddle point approximation and we do not need to perform the path integral for the evaluation of the partition function. In previous studies, it has been assumed that only the minimal-valued saddle point contributes to the EE. In this paper, we propose that all the saddle points contribute comparably but not necessarily equally to the EE by dealing carefully with the semi-classical limit and then the q→1 limit. For example, we numerically evaluate the ERE of two disjoint intervals for the large c Liouville field theory with q∼1. We exploit the BPZ equation with the four twist operators, whose solution is given by the Heun function. We determine the ERE by tuning the behavior of the Heun function such that it becomes consistent with the geometry of the replica manifold. We find the same two saddle points as previous studies for q∼1 in the above system. Then, we provide the ERE for the large but finite c and the q∼1 in case that all the saddle points contribute comparably to the ERE. In particular, the ERE is the summation of these two saddle points by the same weight, due to the symmetry of the system. Based on this work, it shall be of interest to reconsider EE in other semi-classical physical systems with multiple saddle points.

In recent years, the society requires a flexible response of the dental society to deal with changes in disease structure in the super-aging society in Japan. Regarding quality of dental care, we need to ensure quality of clinical environment, dental professionals and the system. As globalization expands, the health care professionals move to another country to work. In the European Union(EU), the quality assurance system for the graduated European dentist through the activities in undergraduate education has been established and a similar approach is ongoing in the region of the Association of South-East Asian Nations. After the registration, the continuing professional development (CPD) system takes a role on quality assurance for dentist. The DentCPD was an approach to create a standard for CPD in the EU. Regarding the quality assurance system in Japanese dentistry, there were systematic approaches, establishing the model core curriculum in dental education, the common achievement test. Besides them, the quality assurance system for dentist has not been established except the voluntary life-long learning program of the Japan Dental Association. Predicting changes of the society to have quality control for dental professionals, we should prepare the system like the CPD system which matches level of the global standard. Keywords: Dental education, Quality assurance, Continuing professional development (CPD)

Despite reports of successful clinical cases, many tumors appear to resist infection by oncolytic viruses (OVs). To circumvent this problem, an armed vesicular stomatitis virus was constructed by inserting a transgene to express Smac/DIABLO during virus infection (VSV-S). Endogenous Smac in HeLa cells was diminished during wtVSV infection, whereas the Smac level was enhanced during VSV-S infection. Apoptosis was readily induced by VSV-S, but not wtVSV, infection. More importantly, the tumor volume was reduced to a larger extent when xenografts of 4T1 cells in BALB/c mice and OV-resistant T-47D cells in nude mice were intratumorally injected with VSV-S. VSV-S represents a novel mechanism to overcome tumor resistance, resulting in more significant tumor regression due to enhanced apoptosis.

Hirayama disease is a distinct type of cervical myelopathy characterized by juvenile onset of unilateral muscular atrophy of a distal upper extremity. We report herein a case with Hirayama disease-like juvenile muscular atrophy involving proximal muscles in the upper extremities. In this case, in the flexion position of the neck, cervical magnetic resonance imaging revealed that the spinal cord was compressed by expansion of the posterior extradural space with forward displacement of the dura matter. These neuroimaging results are identical to those of Hirayama disease. However, the involved muscles in this case were the proximal muscles, unlike Hirayama disease. Five previous cases have displayed this rare subtype of Hirayama disease. The cause of the unique phenotype may be abnormal cervical column alignment, with upper cervical kyphosis producing a higher apex of the vertebral level in a cervical flexion position, resulting in mid-cervical segmental myelopathy.

Background/purpose: Hypertension is a risk factor for stroke and heart disease. Psycho-social reasons are thought to influence blood pressure fluctuation in the dental clinic, but no previous studies have investigated these relationships. In this study, we analyzed a correlation between patients’ blood pressure values and their backgrounds. Materials and methods: We measured blood pressure in 4990 outpatients at our hospital. After determining the age groups in which blood pressure deviated from national averages, patients were classified into the Hypertension group and Normal group. Differences between these groups with regard to the prevalence of systemic disease, dental history and reasons for dental consultation were analyzed. Results: Average systolic blood pressure of males in their 20's, 30's, 40's and females in their 20's, 30's, 40's, 50's was significantly higher than national averages. In these age groups, disease prevalence was significantly higher in the Hypertension group than in the Normal group. Furthermore, the Hypertension group expressed psycho-social reasons for dental consultation more frequently than the Normal group. Conclusion: Relatively younger patients tended to show higher systolic blood pressure. It was suggested that psycho-social backgrounds as well as medical causes influenced the blood pressure increase. Keywords: Hypertension, Biopsychosocial model, First visit medical interview

Using first-principles calculations, this study evaluates the structure, equation of state, and elasticity of three compositions of phase D up to 75 GPa: (1) the magnesium endmember [MgSi2O4(OH)2], (2) the aluminum endmember [Al2SiO4(OH)2], and (3) phase D with 50% Al-substitution [AlMg0.5Si1.5O4(OH)2]. We find that the Mg-endmember undergoes hydrogen-bond symmetrization and that this symmetrization is linked to a 22% increase in the bulk modulus of phase D, in agreement with previous studies. Al2SiO4(OH)2 also undergoes hydrogen-bond symmetrization, but the concomitant increase in bulk modulus is only 13%—a significant departure from the 22% increase of the Mg-endmember. Additionally, Al-endmember phase D is denser (2%–6%), less compressible (6%–25%), and has faster compressional (6%–12%) and shear velocities (12%–15%) relative to its Mg-endmember counterpart. Finally, we investigated the properties of phase D with 50% Al-substitution [AlMg0.5Si1.5O4(OH)2], and found that the hydrogen-bond symmetrization, equation of state parameters, and elastic constants of this tie-line composition cannot be accurately modeled by interpolating the properties of the Mg- and Al-endmembers.

Abstract The stability, structure, and elastic properties of pyrite‐type (FeS2 structured) FeO2H were determined using density functional theory‐based computations with an internally consistent Coulombic self‐interaction term (Ueff). The properties of pyrite‐type FeO2H are compared to that of pyrite‐type AlO2H, with which it likely forms a solid solution at high temperature, as well as the respective lower pressure CaCl2‐type polymorphs of both endmembers: ϵ‐FeOOH and δ‐AlOOH. Due to substantial differences in the CaCl2‐type → pyrite‐type structural transition pressures of these endmembers, the stabilities of the (Al,Fe)O2H solid solution polymorphs are anticipated to be compositionally driven at lower mantle pressures. As the geophysical properties of (Al,Fe)OOH are structurally dependant, interpretations regarding the contribution of pyrite‐type FeO2H to seismically observed features must take into account the importance of this broad phase loop. With this in mind, Fe‐rich pyrite‐type (Al,Fe)OOH may coexist with Al‐dominant CaCl2‐type δ‐(Al,Fe)OOH in the deep Earth. Furthermore, pyrite‐type (Al0.5–0.6,Fe0.4–0.5)O2H can reproduce the reduced compressional and shear velocities characteristic of seismically observed ultra low velocity zones in the Earth's lowermost mantle while Al‐dominant but Fe‐bearing CaCl2‐type δ‐(Al,Fe)OOH may contribute to large low shear velocity provinces.

Inflammation is implicated in the onset and progression of various diseases, including cerebral pathologies. Here, we report that DJ-1, which plays a role within cells as an antioxidant protein, functions as a damage-associated molecular pattern (DAMP) and triggers inflammation if released from dead cells into the extracellular space. We first found that recombinant DJ-1 protein induces the production of various inflammatory cytokines in bone marrow-derived macrophages (BMMs) and dendritic cells (BMDCs). We further identified a unique peptide sequence in the αG and αH helices of DJ-1 that activates Toll-like receptor 2 (TLR2) and TLR4. In the ischemic brain, DJ-1 is released into the extracellular space from necrotic neurons within 24 h after stroke onset and makes direct contact with TLR2 and TLR4 in infiltrating myeloid cells. Although DJ-1 deficiency in a murine model of middle cerebral artery occlusion did not attenuate neuronal injury, the inflammatory cytokine expression in infiltrating immune cells was significantly decreased. Next, we found that the administration of an antibody to neutralize extracellular DJ-1 suppressed cerebral post-ischemic inflammation and attenuated ischemic neuronal damage. Our results demonstrate a previously unknown function of DJ-1 as a DAMP and suggest that extracellular DJ-1 could be a therapeutic target to prevent inflammation in tissue injuries and neurodegenerative diseases.

BackgroundInterprofessional education (IPE) is crucial in dentistry, medicine, and nursing. However, scant mixed methods studies have compared the IPE outcomes across these disciplines to develop evidence-based IPE. This study explored the differences in the readiness of dental, medical, and nursing students for interprofessional learning before and after IPE workshops and elucidated reasons for this disparity.MethodsData were obtained from dental, medical, and nursing students who participated in IPE workshops conducted at Tokyo Medical and Dental University in Japan in 2019 and 2020. The participants filled the validated Japanese version of the Readiness for Interprofessional Learning Scale (RIPLS) before and after attending the workshops (n = 378). Paired t-tests were performed to assess differences between the pre- and post- workshop RIPLS scores. Welch's t-tests were deployed to evaluate interdisciplinary differences in their scores. Qualitative analyses were conducted using an explanatory sequential design with focus group discussions (FGDs) held with 17 dental students to explain the quantitative results.ResultsTotal RIPLS scores increased significantly for every discipline after the workshops (p < 0.001). Dental students scored significantly lower pre- and post- workshop aggregates than medical and nursing students, respectively (p < 0.001). The FGDs yielded three principal themes in the explanations tendered by dental students on their lower scores: 1) dental students rarely felt the need for interprofessional collaborations, 2) dentists often worked without the need for interprofessional collaborations, and 3) dental students believed their contribution to the workshop was insufficient.ConclusionsThe results revealed divergences in the readiness of dental, medical, and nursing students for interprofessional learning, and the study illuminated possible reasons for these disparities. These outcomes will help develop evidence-based IPE by indicating approaches to place a higher value on interprofessional collaborations in educational environments, ameliorate the awareness of educators, and enhance the workshop facilitation style.

Distal radius fracture is a common injury, especially in elderly people, and internal fixation with volar locking plate (VLP) is becoming an increasingly popular technique for the management of displaced and/or unstable distal radius fractures. One of the most common complications of this treatment is the flexor tendon rupture, mostly of the flexor pollicis longus (FPL). While the rupture of flexor digitorum tendons to the index (FDI) mostly occurs concomitantly with the rupture of FPL after the treatment using volar plating for distal radial fracture, sole rupture of the FDI without FPL rupture is very rare. Here, we report a case of the sole rupture of FDI after volar locking plating and analyze its pathogenesis indicating that the lift-up of the distal ulnar edge of the plate related to the malcorrection of the fracture site is the culprit for this specific complication.

Abstract Seismic anomalies observed in Earth's deep mantle are conventionally considered to be associated with thermal and compositional anomalies, and possibly partial melt of major lower‐mantle phases. However, through deep water cycle, impacts of hydrous minerals on geophysical observables and on the deep mantle thermal state and geodynamics remain poorly understood. Here we precisely measured thermal conductivity of δ‐(Al,Fe)OOH, an important water‐carrying mineral in Earth's deep interior, to lowermost mantle pressures at room temperature. The thermal conductivity varies drastically by twofold to threefold across the spin transition of iron, resulting in an exceptionally low thermal conductivity at the lowermost mantle conditions. As δ‐(Al,Fe)OOH is transported to the lowermost mantle, its exceptionally low thermal conductivity may serve as a local thermal insulator, promoting high‐temperature anomalies and the formation of partial melt and thermal plumes at the base of the mantle, strongly influencing thermo‐chemical profiles in the region and fate of Earth's deep water cycle.

A 68-year-old Japanese man presented with Ascaris lumbricoides discharge from his mouth. The infection was suspected to have occurred while the patient was in the Philippines. This A. lumbricoides migration occurred because a proton pump inhibitor was used and Billroth I resection had been performed, which reduced gastric acid secretion and increased gastric pH. In addition, the pylorus had been removed during Billroth I resection, enabling easy access to the stomach. The number of imported foods, of infected migrants and refugees, and of overseas travels is increasing, and these factors may lead to an increase in A. lumbricoides infection even in countries with a typically low incidence of such infections. Clinicians should bear in mind that parasitic infections may occur in nonendemic areas.

IgG4-related hypophysitis, which is the pituitary gland inflammation caused by IgG4 positive lymphocytes, can affect cavernous sinus and orbital apex leading to developing cranial nerve related symptoms such as orbital apex syndrome (OAS). Here we report a case of hypopituitarism associated with OAS caused by pituitary metastasis of the breast cancer with elevated serum IgG4 level, who initially resembled to IgG4-related hypophysitis. Although this case had some features in common with igG4-related hypophysitis. The symptoms and pituitary enlargement were typical. However, steroid treatment did not improve her symptoms. Thus, we performed a tissue biopsy. Histopathologic examination of the hypophyseal tumor confirmed metastatic breast cancer in her pituitary. Pituitary metastatic tumor should be suspected if a case with OAS was once diagnosed as a cancer. Keywords: Orbital apex syndrome, Pituitary metastasis, IgG4-related hypophysitis

Abstract The alkaliphilic, halophilic bacterium Halomonas sp. KM-1 can utilize glucose for the intracellular storage of the bioplastic poly-(R)-3-hydroxybutyric acid (PHB) and extracellular secretion of pyruvate under aerobic conditions. In this study, we investigated the effects of sodium chloride concentration on PHB accumulation and pyruvate secretion in the KM-1 strain and, unexpectedly, observed that oxaloacetate, an important intermediate chemical in the TCA cycle, glycogenesis, and aspartic acid biosynthesis, was secreted. We then further analyzed oxaloacetate productivity after changing the sodium chloride additive concentration, additive time-shift, and culture temperature. In 42-h batch-cultivation experiments, we found that wild-type Halomonas sp. KM-1 secreted 39.0 g/L oxaloacetate at a rate of 0.93 g/(L h). The halophilic bacteria Halomonas has already gained attention for industrial chemical-production processes owing to its unique properties, such as contamination-free culture conditions and a tolerance for high substrate concentrations. Moreover, no commercial scale oxaloacetate production was previously reported to result from bacterial fermentation. Oxaloacetate is an important intermediate chemical in biosynthesis and is used as a health food based on its role in energy synthesis. Thus, these data provided important insights into the production of oxaloacetate and other derivative chemicals using this strain.

Mycobacterium tuberculosis (MTB) can disseminate to extrapulmonary organs, particularly in severely immunosuppressed patients. Confirmation of active MTB infection is often difficult in subjects with a contraindication for invasive procedures. A case of disseminated MTB infection after hematopoietic stem cell transplantation is reported herein. Circulating cell-free DNA from the patient showed positive amplification of an MTB complex-specific sequence using a digital PCR technique. The MTB infection was confirmed by positive acid-fast staining and an approved quantitative PCR assay using liver tissue obtained at autopsy. The detection of MTB in circulating cell-free DNA using this technique may represent a less invasive diagnostic tool for pulmonary and extrapulmonary MTB infections.

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a debilitating, progressive disease without effective treatment; therefore, development of disease modifying therapy that improves long-term functional outcomes is an unmet need for patients. However, it is virtually impossible to consider this as a primary endpoint in clinical trials owing to the prolonged disease course. Therefore, development of surrogate markers that help predict the effectiveness of new interventions is essential. Currently, several candidate surrogate markers have been identified for HAM/TSP. Cerebrospinal fluid (CSF) C-X-C motif chemokine 10 (CXCL10) is involved in the pathogenesis of HAM/TSP and was shown to correlate with disease progression. However, it remains unclear whether changes in CSF CXCL10 levels are observed in response to treatment and whether these correlate with prognosis. Here we investigated several markers, including CSF CXCL10, in this respect. Data pertaining to patient characteristics and results of motor function evaluation and CSF examination of 13 HAM/TSP patients who received steroid treatment were retrospectively analyzed. Osame motor disability scores (OMDS), 10 m walking time, and CSF levels of CXCL10, neopterin, total protein, cell counts, and anti-HTLV-1 antibody titer were compared before and after steroid therapy. Levels of all CSF markers, with the exception of cell count, were significantly decreased after treatment. Nine of the 13 patients (69.2%) showed improvement in OMDS and were considered responders. Pre-treatment CSF levels of CXCL10 and anti-HTLV-1 antibody titer in responders were higher than those in non-responders (p = 0.020 and p = 0.045, respectively). Patients who continued low-dose oral prednisolone maintenance therapy after methylprednisolone pulse therapy showed sustained improvement in OMDS and CSF CXCL10 and neopterin levels lasting for 2 years. In contrast, OMDS and the CSF marker levels in patients who discontinued treatment returned to pre-treatment levels. This rebound phenomenon was also observed in patients who discontinued oral prednisolone therapy independently of pulse therapy. Our findings suggest that CSF CXCL10 may serve as a therapy-response and therapy-predictive marker for HAM/TSP. In addition, since decrease in CSF CXCL10 level was associated with good functional prognosis, CSF CXCL10 is a potential surrogate marker for treatment of HAM/TSP.

The Ryu–Takayanagi formula provides the entanglement entropy of quantum field theory as an area of the minimal surface (Ryu–Takayanagi surface) in a corresponding gravity theory. There are some attempts to understand the formula as a flow rather than as a surface. In this paper, we consider null rays emitted from the AdS boundary and construct a flow representing the causal holographic information. We present a sufficient and necessary condition that the causal information surface coincides with Ryu–Takayanagi surface. In particular, we show that, in spherical symmetric static spacetimes with a negative cosmological constant, wave fronts of null geodesics from a point on the AdS boundary become extremal surfaces and therefore they can be regarded as the Ryu–Takayanagi surfaces. In addition, from the viewpoint of flow, we propose a wave optical formula to calculate the causal holographic information.

Carbonate minerals such as ferromagnesite (Mg,Fe)CO 3 are suggested to be a possible major deep-carbon host in the lower mantle, because ferromagnesite is possibly stabilized by Fe spin crossover under pressure. However, the behavior of Fe-bearing carbonates under lower mantle pressure conditions has not been suitably examined thus far. Thus, in this study, we investigate the high-pressure stability of ferromagnesite and possible high-pressure structures with the chemical composition of (Mg 0.833 Fe 0.167 )CO 3 via first principles calculation using internally consistent local density approximation with Hubbard parameter (LDA+U) method, which can more accurately account for the electronic state of Fe than the LDA and generalized gradient approximation (GGA) approaches. The enthalpy values obtained via our calculations suggest that (Mg 0.833 Fe 0.167 )CO 3 undergoes phase transition from the R 3 ¯ c structure (high spin) to the P 1 ¯ (high spin) at 50 GPa, and to C2/m (high-spin) structure above 80 GPa, under static 0 K conditions. Therefore, no spin transitions in these carbonate minerals is expected under the lower mantle pressure conditions.

Mammalian neural stem/progenitor cells (NSPCs) sequentially generate neurons and glia during CNS development. Here we identified miRNA-153 (miR-153) as a modulator of the temporal regulation of NSPC differentiation. Overexpression (OE) of miR-153 delayed the onset of astrogliogenesis and maintained NSPCs in an undifferentiated state in vitro and in the developing cortex. The transcription factors nuclear factor I (NFI) A and B, essential regulators of the initiation of gliogenesis, were found to be targets of miR-153. Inhibition of miR-153 in early neurogenic NSPCs induced precocious gliogenesis, whereas NFIA/B overexpression rescued the anti-gliogenic phenotypes induced by miR-153 OE. Our results indicate that miR-mediated fine control of NFIA/B expression is important in the molecular networks that regulate the acquisition of gliogenic competence by NSPCs in the developing CNS.

Over the course of evolution, the acquisition of novel structures has ultimately led to wide variation in morphology among extant multicellular organisms. Thus, the origins of genetic systems for new morphological structures are a subject of great interest in evolutionary biology. The larval skeleton is a novel structure acquired in some echinoderm lineages via the activation of the adult skeletogenic machinery. Previously, VEGF signaling was suggested to have played an important role in the acquisition of the larval skeleton. In the present study, we compared expression patterns of Alx genes among echinoderm classes to further explore the factors involved in the acquisition of a larval skeleton. We found that the alx1 gene, originally described as crucial for sea urchin skeletogenesis, may have also played an essential role in the evolution of the larval skeleton. Unlike those echinoderms that have a larval skeleton, we found that alx1 of starfish was barely expressed in early larvae that have no skeleton. When alx1 overexpression was induced via injection of alx1 mRNA into starfish eggs, the expression patterns of certain genes, including those possibly involved in skeletogenesis, were altered. This suggested that a portion of the skeletogenic program was induced solely by alx1. However, we observed no obvious external phenotype or skeleton. We concluded that alx1 was necessary but not sufficient for the acquisition of the larval skeleton, which, in fact, requires several genetic events. Based on these results, we discuss how the larval expression of alx1 contributed to the acquisition of the larval skeleton in the putative ancestral lineage of echinoderms.

New inhibitors of influenza viruses are needed to combat the potential emergence of novel human influenza viruses. We have identified a class of small molecules that inhibit replication of influenza virus at picomolar concentrations in plaque reduction assays. The compound also inhibits replication of vesicular stomatitis virus. Time of addition and dilution experiments with influenza virus indicated that an early time point of infection was blocked and that inhibitor 136 tightly bound to virions. Using fluorescently labeled influenza virus, inhibition of viral fusion to cellular membranes by blocked lipid mixing was established as the mechanism of action for this class of inhibitors. Stabilization of the neutral pH form of hemagglutinin (HA) was ruled out by trypsin digestion studies in vitro and with conformation specific HA antibodies within cells. Direct visualization of 136 treated influenza virions at pH 7.5 or acidified to pH 5.0 showed that virions remain intact and that glycoproteins become disorganized as expected when HA undergoes a conformational change. This suggests that exposure of the fusion peptide at low pH is not inhibited but lipid mixing is inhibited, a different mechanism than previously reported fusion inhibitors. We hypothesize that this new class of inhibitors intercalate into the virus envelope altering the structure of the viral envelope required for fusion to cellular membranes.

In this study the author undertook a micro-level analysis of the relationship between land-ownership change and the growth process of Sapporo city. The most important questions addressed by this paper are: Why the process occurred?; When did it occur?; Where did it take place?; Who was responsible?; and, How was it conducted? The author analyzed the long-term process of building supply and revealed how many renovation cases were identi-fied that were brought about by newly advanced land purchasers, and how many cases were brought about by original land-owners without land-ownership change.

The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ∼50 mm were recovered from rescue workers' lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways.Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM(10-53) or WTC-PM(2.5) at concentrations of 10, 50 or 100 µg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM(10-53) and PM(2.5). GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM(10-53) and in sera of WTC dust-exposed subjects (n = 70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM(10-53) consistently induced more cytokine release than WTC-PM(2.5) at 100 µg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC.WTC-PM(10-53) induced a stronger inflammatory response by human AM than WTC-PM(2.5). This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure.

A umidade do solo é um conceito físico simples, mas a sua determinação apresenta algumas dificuldades. Dentre os métodos de determinação da umidade, destaca-se o TDR (Time Domain Reflectometry), por ser um método indireto, não destrutivo, rápido, supostamente pouco dependente dos fatores locais e bastante preciso. No entanto, existem indícios da influência de fatores externos sobre a sua operação, o que torna necessária a calibração local. Particularmente para solos tropicais, pouco se sabe a respeito da sua utilização. Este trabalho teve como objetivo avaliar um equipamento TDR para uso em um Nitossolo Vermelho Distroférrico, da região Noroeste do Estado do Paraná, avaliando a influência da instalação das sondas e de características de cada sonda, sobre as curvas de calibração. As diferenças entre sondas não influenciaram na calibração para este solo. Por outro lado, o contato solo - sonda, que varia conforme a instalação, pode influenciar na medida de umidade realizada com o uso desta técnica

Natural nanofibers are widely used in the field of medicine, but the low strength of these nanofibers is one of the major concerns. A number of factors, importantly the composition, affect the strength of natural nanofibers. The purpose of the current study is to ascertain the effect of the composition of natural nanofibers on the strength of hybrid composites formed using these nanofibers. Hybrid composites formed using 32% volume glass fibre with optimized volume fraction of 0.5% of pure Cellulose Acetate (CA), and 0.5% CA + Hemp Seed (HS) for this study to carry out the analysis. Hybrid composites were produced with vacuum-assisted resin transfer molding (VARTM) by collecting natural nanofibers, produced using the electrospinning process, over glass fiber mats. The electrospinning process was carried out with 12 kV, 10 cm tip to the collector gap, and 12% concentration of the solution. The tensile strength of the hybrid composites was measured using the universal testing machine (UTM). The results showed that the diameter of the electrospun nanofiber varied between 50 and 1400 nm and was affected by solution concentration, voltage, tip-to-collector distance, flow rate, and inclusion of HS in CA. The inclusion of HS in CA, for all compositions, decreased the fiber diameter and caused the formation of beads prominently at higher concentrations. Hybrid composites formed from nanofibers produced using CA and HS showed higher elastic modulus (232 MPa) and tensile strength (20.4 GPa) as compared with nanofibers produced using CA only (elastic modulus = 110 MPa and 13.7 GPa).

Titanium has a significant potential for the cryogenic industrial fields such as aerospace and liquefied gas storage and transportation due to its excellent low temperature properties. To develop and advance the technologies in cryogenic industries, it is required to fully understand the underlying deformation mechanisms of Ti under the extreme cryogenic environment. Here, we report a study of the lattice behaviour in grain families of Grade 2 CP-Ti during in-situ neutron diffraction test in tension at temperatures of 15-298 K. Combined with the neutron diffraction intensity analysis, EBSD measurements revealed that the twinning activity was more active at lower temperature, and the behaviour was complicated with decreasing temperature. The deviation of linearity in the lattice strains was caused by the load-redistribution between plastically soft and hard grain families, resulting in the three-stage hardening behaviour. The lattice strain behaviour further deviated from linearity with decreasing temperature, leading to the transition of plastically soft-to-hard or hard-to-soft characteristic of particular grain families at cryogenic temperature. The improvement of ductility can be attributed to the increased twinning activity and a significant change of lattice deformation behaviour at cryogenic temperature., (© 2022. The Author(s).)