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Abstract Background The placenta is essential for nutrient exchange and hormone production between the mother and the developing fetus and serves as an invaluable model for epigenetic research. Most epigenetic studies of the human placenta have used whole placentas from term pregnancies and have identified the presence of partially methylated domains (PMDs). However, the origin of these domains, which are typically absent in most somatic cells, remains unclear in the placental context. Results Using whole-genome bisulfite sequencing and analysis of histone H3 modifications, we generated epigenetic profiles of human cytotrophoblasts during the first trimester and at term, as well as human trophoblast stem cells. Our study focused specifically on PMDs. We found that genomic regions likely to form PMDs are resistant to global DNA demethylation during trophectoderm reprogramming, and that PMDs arise through a slow methylation process within condensed chromatin near the nuclear lamina. In addition, we found significant differences in histone H3 modifications between PMDs in cytotrophoblasts and trophoblast stem cells. Conclusions Our findings suggest that spatiotemporal genomic features shape megabase-scale DNA methylation patterns, including PMDs, in the human placenta and highlight distinct differences in PMDs between human cytotrophoblasts and trophoblast stem cells. These findings advance our understanding of placental biology and provide a basis for further research into human development and related diseases.

Abstract Real-world work environments require operators to perform multiple tasks with continual support from an automated system. Eye movement is often used as a surrogate measure of operator attention, yet conventional summary measures such as percent dwell time do not capture dynamic transitions of attention in complex visual workspace. This study analyzed eye movement data collected in a controlled a MATB-II task environment using gaze transition entropy analysis. In the study, human subjects performed a compensatory tracking task, a system monitoring task, and a communication task concurrently. The results indicate that both gaze transition entropy and stationary gaze entropy, measures of randomness in eye movements, decrease when the compensatory tracking task required more continuous monitoring. The findings imply that gaze transition entropy reflects attention allocation of operators performing dynamic operational tasks consistently.

Cryogenic heat exchangers are important for vaporizing liquefied natural gas or liquefied hydrogen and utilizing their cryogenic energy, but frost formation causes severe problems that deteriorate performance. Frost formation on a cryogenic surface is characterized by simultaneous mist formation. However, the detailed frosting mechanisms, especially the interaction between frost and mist formation under forced convection, have not been revealed. In this study, we experimentally observed the frost and mist formation on a flat plate under forced convection over a wide range of cooling surface temperatures (Tw), from general-low to cryogenic. The frost and mist layer height was quantitatively measured with a white LED and a laser sheet light source in addition to the frosting amount. As a result, the frosting style was classified into three groups depending on the cooling surface temperature under the air temperature of 27°C, air humidity of 12 g/m3, and air velocity of 2.0 m/s. When Tw ≥ −75°C, the mist was hardly generated, and needle-shape or dendric frost formed by desublimation almost uniformly on the entire plate surface. On the other hand, frost is not uniformly formed in the flow direction at Tw ≤ −100°C. Frost hill is formed by desublimation at the leading edge and protrudes higher as the cooling surface temperature is lower. The high frost hill leads to the flow detachment behind it and the persistent mist generation, affecting the frost growth on the rear. Thus, under forced convection, the frost hill shape and the flow detachment behind it are important factors determining the frosting style.

Abstract The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Aim There are few assessments of sedatives during the acute phase under sedation protocols for patients with sepsis. We aimed to compare the influence of different sedation strategies using midazolam and propofol under light sedation on clinical outcomes of ventilated patients with sepsis. Methods This study was a post‐hoc analysis of data from the dexmedetomidine for sepsis in the ICU Randomized Evaluation (DESIRE) trial. Patients were divided into propofol and midazolam groups based on continuously used drug, and sedation control between groups compared on day three. We assessed the incidence of delirium, length of ICU stay, number of ventilator‐free days within the first 28 days, and mortality after 28 days. Results The midazolam and propofol groups consisted of 51 and 66 patients, respectively. Both groups had similar characteristics, except for age and emergency surgery. The number of well‐controlled sedation patients in the propofol group on day three was significantly higher than that in the midazolam group (odds ratio [OR] 3.9, 95% CI [1.30, 11.7]). The incidence of daily coma and delirium within the initial week was different between groups and increased with midazolam administration (P = 0.0138). The number of Confusion Assessment Method for ICU‐positive patients was significantly higher in the midazolam group than in the propofol group (OR 5.71, 95% CI [2.30, 14.2]). Conclusion In patients with sepsis required mechanical ventilation, sedation with midazolam based on a light sedation protocol may be associated with inappropriate sedation during the acute phase, with increased coma and delirium as compared to propofol.

The development of a numerical analysis of fuel atomization is important for engine design but has the problem that the required resolutions for the gas phase and atomized droplets are significantly different. To solve this, an Euler-Lagrange coupling numerical analysis for fuel atomization has been developed. For the improvement of this analysis by including the shape effect of atomized droplets and increasing the number of droplets that can be replaced by Lagrange particles, a new droplet shape representation method using five shape parameters — Sphericity, Bentness, Slenderness, Flatness and Complexity — are proposed. These parameters are defined based on indices that reflect the overall scale of droplets, such as volume and area, and the local distribution of shape features within a droplet. First, a test case with ideal geometries showed how well these parameters qualitatively and quantitatively represent the characteristics of droplet shapes. Then, the distribution of droplet shapes in a crossflow computed by a detailed numerical analysis using the S-CLSVOF method was analyzed by the proposed shape representation method. As a result, it was shown that the parameters expressed the characteristics of actual droplets sampled from the analysis. In addition, it was confirmed that the shape distributions expressed by the proposed five parameters differed depending on the density ratio of gas and liquid and/or the Weber number, and that the analysis result is consistent with the theories of surface tension and linear instability.

BackgroundSince 2020, peoples’ lifestyles have been largely changed due to the COVID-19 pandemic worldwide. In the medical field, although many patients prefer remote medical care, this prevents the physician from examining the patient directly; thus, it is important for patients to accurately convey their condition to the physician. Accordingly, remote medical care should be implemented and adaptable home medical devices are required. However, only a few highly accurate home medical devices are available for automatic wheeze detection as an exacerbation sign. ObjectiveWe developed a new handy home medical device with an automatic wheeze recognition algorithm, which is available for clinical use in noisy environments such as a pediatric consultation room or at home. Moreover, the examination time is only 30 seconds, since young children cannot endure a long examination time without crying or moving. The aim of this study was to validate the developed automatic wheeze recognition algorithm as a clinical medical device in children at different institutions. MethodsA total of 374 children aged 4-107 months in pediatric consultation rooms of 10 institutions were enrolled in this study. All participants aged ≥6 years were diagnosed with bronchial asthma and patients ≤5 years had reported at least three episodes of wheezes. Wheezes were detected by auscultation with a stethoscope and recorded for 30 seconds using the wheeze recognition algorithm device (HWZ-1000T) developed based on wheeze characteristics following the Computerized Respiratory Sound Analysis guideline, where the dominant frequency and duration of a wheeze were >100 Hz and >100 ms, respectively. Files containing recorded lung sounds were assessed by each specialist physician and divided into two groups: 177 designated as “wheeze” files and 197 as “no-wheeze” files. Wheeze recognitions were compared between specialist physicians who recorded lung sounds and those recorded using the wheeze recognition algorithm. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value for all recorded sound files, and evaluated the influence of age and sex on the wheeze detection sensitivity. ResultsDetection of wheezes was not influenced by age and sex. In all files, wheezes were differentiated from noise using the wheeze recognition algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value of the wheeze recognition algorithm were 96.6%, 98.5%, 98.3%, and 97.0%, respectively. Wheezes were automatically detected, and heartbeat sounds, voices, and crying were automatically identified as no-wheeze sounds by the wheeze recognition algorithm. ConclusionsThe wheeze recognition algorithm was verified to identify wheezing with high accuracy; therefore, it might be useful in the practical implementation of asthma management at home. Only a few home medical devices are available for automatic wheeze detection. The wheeze recognition algorithm was verified to identify wheezing with high accuracy and will be useful for wheezing management at home and in remote medical care.

BackgroundThe distribution of body mass in populations of Western countries differs from that of populations of East Asian countries. In East Asian countries, fewer people have a high body mass index than those in Western countries. In Japan, the country with the highest number of older adults worldwide, many people have a low body mass index. Therefore, this study aimed to determine the association between a low body mass index and mortality in patients with sepsis in Japan.MethodsWe conducted this retrospective analysis of 548 patients with severe sepsis from a multicenter prospective observational study. Multivariate logistic regression analyses determined the association between body mass index and 28-day mortality adjusted for age, sex, pre-existing conditions, the occurrence of septic shock, Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment scores. Furthermore, the association between a low body mass index and 28-day mortality was analyzed.ResultsThe low body mass index group represented 18.8% of the study population (103/548); the normal body mass index group, 57.3% (314/548); and the high body mass index group, 23.9% (131/548), with the 28-day mortality rates being 21.4% (22/103), 11.2% (35/314), and 14.5% (19/131), respectively. In the low body mass index group, the crude and adjusted odds ratios (95% confidence intervals) for 28-day mortality relative to the non-low body mass index (normal and high body mass index groups combined) group were 2.0 (1.1-3.4) and 2.3 (1.2-4.2), respectively.ConclusionA low body mass index was found to be associated with a higher 28-day mortality than the non-low body mass index in patients with sepsis in Japan. Given that older adults often have a low body mass index, these patients should be monitored closely to reduce the occurrence of negative outcomes.

Aim There are no definitive data to determine whether age influences the effects of dexmedetomidine (DEX) treatment. Thus, we investigated whether older age was associated with more favorable sedative action by DEX in sepsis patients who required mechanical ventilation. Methods This study involved a post‐hoc analysis of data from the Dexmedetomidine for Sepsis in the ICU Randomized Evaluation (DESIRE) trial. The patients were categorized based on median age into elderly and younger groups. The two groups were then compared during the first 7 days after ventilation based on proportion of patients with well‐controlled sedation (Richmond Agitation–Sedation Scale score between −3 and +1), days free from delirium (based on the Confusion Assessment Method for ICU), and days free from coma (Richmond Agitation–Sedation Scale score between −4 and −5). Results One hundred and one patients were assigned to the elderly group and 100 patients were assigned to the younger group. In the elderly group, 50 patients received DEX treatment and 51 patients received non‐DEX treatment, with the DEX arm having significantly better‐controlled sedation (range, 14–52% versus 16–27%; P = 0.01). In the younger group, 50 patients received DEX treatment and 50 patients received non‐DEX treatment, with no significant difference in the proportions of well‐controlled sedation (range, 20–64% versus 24–60%; P = 0.73). There were no significant differences in the numbers of days free from delirium or coma between the groups. Conclusion In elderly sepsis patients who require ventilation, dexmedetomidine could be more effective than other sedative agents for achieving proper sedation.

In this study, a technique that uses a capacitance sensor with an asymmetric electrode to measure the void fraction of a refrigerant was developed. It is known that the void fraction and flow pattern affect the measured capacitance. Therefore, the relationship between the void fraction and capacitance is not linear; hence, a calibration method for obtaining accurate measurements is necessary. A calibration method was designed in this study based on repeated capacitance measurements and the bimodal temporal distribution to calibrate the atypical and repetitive flow patterns of slug flow and its transition to the intermittent flow regime. The calibration method also considers the weighted-average relation for the gradual transition of the intermittent to annular flow pattern according to the change from low to high quality. The proposed method was experimentally analyzed under the conditions of R32 refrigerant, a tube inner diameter of 7.1 mm, saturation temperature of 25 °C, mass flux of 100–400 kg m−2 s−1, and vapor quality of 0.025–0.900, and it was validated using a quick-closing valve (QCV) system under identical conditions. A relative error of 2.99% was obtained for the entire system, indicating good agreement between the proposed and QCV-based methods.

In an effort to tackle environmental problems, sustainable policies that have a low environmental impact on the local community are being implemented in many countries, including Japan. One approach is the smart community, which is a policy to evaluate the cost of the entire community, considering each interaction while dividing society into seven fields: power, gas, water, railway, industry, business, and home models. In this study, we evaluate and optimize the home model. We develop an optimization model for the operation plan of energy storage equipment in a residential building as part of a smart community. The purpose of this model is to improve electricity costs from the demand profile and provide stable power supply from the supply profile. Therefore, this model controls the operation of energy storage equipment and also performs load leveling. It is intended to reduce the total power consumption during peak hours by operating the energy storage equipment at night, when the usage of other electrical appliances is low. A stochastic programming model is formulated using scenarios that represent the uncertainty of power and heat demand. This formulation assumes continuous operation in a residential building. We demonstrate the usefulness of the stochastic programming model by comparing it with the deterministic model. As an economic assessment, we compare the daily beneficial expense of the existing model with our new model of daily operations by following the improvement factors. Our model not only lowers peak total power consumption but also achieves load leveling. The total operating time of energy storage equipment is also reduced.

Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities in vitro were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.

BackgroundThe detection of wheezes as an exacerbation sign is important in certain respiratory diseases. However, few highly accurate clinical methods are available for automatic detection of wheezes in children. This study aimed to develop a wheeze detection algorithm for practical implementation in children.MethodsA wheeze recognition algorithm was developed based on wheezes features following the Computerized Respiratory Sound Analysis guidelines. Wheezes can be detected by auscultation with a stethoscope and using an automatic computerized lung sound analysis. Lung sounds were recorded for 30 s in 214 children aged 2 months to 12 years and 11 months in a pediatric consultation room. Files containing recorded lung sounds were assessed by two specialist physicians and divided into two groups: 65 were designated as "wheeze" files, and 149 were designated as "no-wheeze" files. All lung sound judgments were agreed between two specialist physicians. We compared wheeze recognition between the specialist physicians and using the wheeze recognition algorithm and calculated the sensitivity, specificity, positive predictive value, and negative predictive value for all recorded sound files to evaluate the influence of age on the wheeze detection sensitivity.ResultsThe detection of wheezes was not influenced by age. In all files, wheezes were differentiated from noise using the wheeze recognition algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value of the wheeze recognition algorithm were 100%, 95.7%, 90.3%, and 100%, respectively.ConclusionsThe wheeze recognition algorithm could identify wheezes in sound files and therefore may be useful in the practical implementation of respiratory illness management at home using properly developed devices.

Recent developments in formal verification have identified approximate liftings (also known as approximate couplings) as a clean, compositional abstraction for proving differential privacy. This construction can be defined in two styles. Earlier definitions require the existence of one or more witness distributions, while a recent definition by Sato uses universal quantification over all sets of samples. These notions have each have their own strengths: the universal version is more general than the existential ones, while existential liftings are known to satisfy more precise composition principles. We propose a novel, existential version of approximate lifting, called $\star$-lifting, and show that it is equivalent to Sato's construction for discrete probability measures. Our work unifies all known notions of approximate lifting, yielding cleaner properties, more general constructions, and more precise composition theorems for both styles of lifting, enabling richer proofs of differential privacy. We also clarify the relation between existing definitions of approximate lifting, and consider more general approximate liftings based on $f$-divergences.

Abstract Background Head spot is one of the phenotypes identified in the KFRS4/Kyo rat strain. Although previous linkage analysis suggested that Ednrb, which is frequently involved in coat color variations in various animals, could be the gene responsible for this phenotype, no mutations have been identified in its coding region. Results To identify mutations causative of this phenotype in KFRS4/Kyo, we analyzed target capture sequencing data that we recently generated. Our target capture method has a unique feature, i.e., it covers not only exonic regions but also conserved non-coding sequences (CNSs) among vertebrates; therefore, it has the potential to detect regulatory mutations. We identified a deletion of approximately 50 kb in length approximately 50 kb upstream of Ednrb. A comparative analysis with the epigenomic data in the corresponding region in humans and mice showed that one of the CNSs might be an enhancer. Further comparison with Hi-C data, which provide information about chromosome conformation, indicated that the putative enhancer is spatially close to the promoter of Ednrb, suggesting that it acts as an enhancer of Ednrb. Conclusions These in silico data analyses strongly suggest that the identified deletion in the intergenic region upstream of Ednrb, which might contain a melanocyte-specific enhancer, is the mutation causative of the head spot phenotype in the KFRS4/Kyo rat strain.

With the recent surge of affordable, high-performance virtual reality (VR) headsets, there is unlimited potential for applications ranging from education, to training, to entertainment, to fitness and beyond. As these interfaces continue to evolve, passive user-state monitoring can play a key role in expanding the immersive VR experience, and tracking activity for user well-being. By recording physiological signals such as the electroencephalogram (EEG) during use of a VR device, the user's interactions in the virtual environment could be adapted in real-time based on the user's cognitive state. Current VR headsets provide a logical, convenient, and unobtrusive framework for mounting EEG sensors. The present study evaluates the feasibility of passively monitoring cognitive workload via EEG while performing a classical n-back task in an interactive VR environment. Data were collected from 15 participants and the spatio-spectral EEG features were analyzed with respect to task performance. The results indicate that scalp measurements of electrical activity can effectively discriminate three workload levels, even after suppression of a co-varying high-frequency activity.

The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and Imd-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, we found many immunoresponsive genes, including those encoding AMPs, to be upregulated in these mutants. Downregulation of these pathways by either a Toll or imd mutation enhanced the tumour phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress the progression of haematopoietic tumours by inducing AMP gene expression. Overexpression of any one of the five AMPs studied resulted in enhanced apoptosis in mutant LGs, whereas no apoptotic signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.

Summary: Placental development is a key event in mammalian reproduction and embryogenesis. However, the molecular basis underlying placental development is not fully understood. Here, we conduct a forward genetic screen to identify regulators for extraembryonic development and identify Zfp281 as a key factor. Zfp281 overexpression in mouse embryonic stem cells facilitates the induction of trophoblast stem-like cells. Zfp281 is preferentially expressed in the undifferentiated trophoblast stem cell population in an FGF-dependent manner, and disruption of Zfp281 in mice causes severe defects in early placental development. Consistently, Zfp281-depleted trophoblast stem cells exhibit defects in maintaining the transcriptome and differentiation capacity. Mechanistically, Zfp281 interacts with MLL or COMPASS subunits and occupies the promoters of its target genes. Importantly, ZNF281, the human ortholog of this factor, is required to stabilize the undifferentiated status of human trophoblast stem cells. Thus, we identify Zfp281 as a conserved factor for the maintenance of trophoblast stem cell plasticity. : Ishiuchi et al. demonstrate that Zfp281 regulates gene expression through the interaction with MLL or COMPASS in trophoblast stem (TS) cells. Depletion of Zfp281 impairs TS cell plasticity in vitro and in vivo. Knockdown of ZNF281 downregulates a set of genes enriched in undifferentiated human TS cells, including ELF5 and LIN28A. Keywords: Zfp281, trophoblast stem cell, placental development, MLL-COMPASS

We report sequence data obtained by our recently devised target capture method TargetEC applied to 20 inbred rat strains. This method encompasses not only all annotated exons but also highly conserved non-coding sequences shared among vertebrates. The total length of the target regions covers 146.8 Mb. On an average, we obtained 31.7× depth of target coverage and identified 154,330 SNVs and 24,368 INDELs for each strain. This corresponds to 470,037 unique SNVs and 68,652 unique INDELs among the 20 strains. The sequence data can be accessed at DDBJ/EMBL/GenBank under accession number PRJDB4648, and the identified variants have been deposited at http://bioinfo.sls.kyushu-u.ac.jp/rat_target_capture/20_strains.vcf.gz.

Background Statins reduce aneurysm growth in mouse models of Marfan syndrome, although the mechanism is unknown. In addition to reducing cholesterol, statins block farnesylation and geranylgeranylation, which participate in membrane‐bound G‐protein signaling, including Ras. We dissected the prenylation pathway to define the effect of statins on aneurysm reduction. Methods and Results Fbn1C1039G/+ mice were treated with (1) pravastatin (HMG‐CoA [3‐hydroxy‐3‐methylglutaryl coenzyme A] reductase inhibitor), (2) manumycin A (MA; FPT inhibitor), (3) perillyl alcohol (GGPT1 and ‐2 inhibitor), or (4) vehicle control from age 4 to 8 weeks and euthanized at 12 weeks. Histological characterization was performed. Protein analysis was completed on aortic specimens to measure ERK (extracellular signal‐regulated kinase) signaling. In vitro Fbn1C1039G/+ aortic smooth muscle cells were utilized to measure Ras‐dependent ERK signaling and MMP (matrix metalloproteinase) activity. Pravastatin and MA significantly reduced aneurysm growth compared with vehicle control (n=8 per group). In contrast, PA did not significantly decrease aneurysm size. Histology illustrated reduced elastin breakdown in MA‐treated mice compared with vehicle control (n=5 per group). Although elevated in control Marfan mice, both phosphorylated c‐Raf and phosphorylated ERK1/2 were significantly reduced in MA‐treated mice (4–5 per group). In vitro smooth muscle cell studies confirmed phosphorylated cRaf and phosphorylated ERK1/2 signaling was elevated in Fbn1C1039G/+ smooth muscle cells (n=5 per group). Fbn1C1039G/+ smooth muscle cell Ras‐dependent ERK signaling and MMP activity were reduced following MA treatment (n=5 per group). Corroborating in vitro findings, MMP activity was also decreased in pravastatin‐treated mice. Conclusions Aneurysm reduction in Fbn1C1039G/+ mice following pravastatin and MA treatment was associated with a decrease in Ras‐dependent ERK signaling. MMP activity can be reduced by diminishing Ras signaling.

We introduce a method to lift monads on the base category of a fibration to its total category. This method, which we call codensity lifting, is applicable to various fibrations which were not supported by its precursor, categorical TT-lifting. After introducing the codensity lifting, we illustrate some examples of codensity liftings of monads along the fibrations from the category of preorders, topological spaces and extended pseudometric spaces to the category of sets, and also the fibration from the category of binary relations between measurable spaces. We also introduce the dual method called density lifting of comonads. We next study the liftings of algebraic operations to the codensity liftings of monads. We also give a characterisation of the class of liftings of monads along posetal fibrations with fibred small meets as a limit of a certain large diagram.

Imaging was conducted using an electron tracking-Compton camera (ETCC), which measures γ-rays with energies in the range of 200-900 keV from 95mTc. 95mTc was produced by the 95Mo(p, n)95mTc reaction on a 95Mo-enriched target. A method for recycling 95Mo-enriched molybdenum trioxide was employed, and the recycled yield of 95Mo was 70%-90%. Images were obtained with the gate of three energies. The results showed that the spatial resolution increases with increasing γ-ray energy, and suggested that the ETCC with high-energy γ-ray emitters such as 95mTc is useful for the medical imaging of deep tissue and organs in the human body.

Objectives: The prevalence of aortic valve disease is increasing. The purpose of this study was to compare the outcomes of patients undergoing ministernotomy versus conventional full sternotomy for aortic valve replacement (AVR). Materials and Methods: Between May 2009 and November 2013, 59 consecutive patients underwent AVR in our institution; 27 patients received upper ministernotomy (Group M), and 32 received conventional median full sternotomy (Group F). Pre-operative characteristics, aortic valve pathology, and left ventricular function in both groups were similar. Results: No differences were found in mean operation time, volume of blood loss, mean cardiopulmonary time, aortic clamp time, transfusion rate, or mortality and morbidity rates. However, the amount of red blood cells used in transfusion was significantly less in Group F than in Group M (7.3 +/- 4.5 vs. 4.6 +/- 3.3 units, P = 0.015). Conclusions: Although ministernotomy can be safely used for AVR without prolonging operative or cardiopulmonary time, no significant advantages were discerned for choosing ministernotomy over conventional full median sternotomy. [Arch Clin Exp Surg 2015; 4(2.000): 69-73]

A capacitance-based void fraction sensor has been developed for the rocket or airbreathing engines, which is simple and do not disturb the flow. Typical conventional sensors usually have two concave electrodes mounted on the outer wall of the dielectric tube. They are relatively low accuracy if they have a noise shield; the maximum measurement error is over 30% in our research. The aim of this study is to improve the measurement accuracy while keeping the advantage of simplicity, mountability and non-intrusive characteristics. A theoretical formulae and electromagnetic field analysis, EFA, are used to design the sensors and are compared to an experiment using air/silicon-oil mixture flow. As the result, a newly developed asymmetrical type sensor which consists of asymmetric flat electrodes with side walls shows good performance; the inaccuracy between true void fraction and measured void fraction is 6% for the stratified flow.

A 15-year-old boy was referred to our hospital for further investigation and treatment of sternal osteomyelitis due to blunt chest trauma, more specifically elbowing during a basketball game 19 days earlier. On an initial presentation, his chest was markedly swollen and chest computed tomography demonstrated a sternal fracture and massive fluid collection in the chest wall. Since his general condition remained fairly good, we initially selected minimal drainage concomitant with antibiotics; if it was unsuccessful, we planned to switch to a more radical debridement procedure. The patient recovered without further invasive intervention and was discharged on postoperative day 26. There is no sign of recurrence six months after operation. This case report indicates that minimal drainage would be a good option for treatment in a phased strategy.