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To report preliminary outcomes of high dose image-guided intensity modulated radiotherapy (IG-IMRT) in the treatment of chordomas of the sacrum, mobile spine and skull base.Retrospective analysis of chordoma patients treated with surgery and/or radiotherapy (RT) in a single tertiary cancer center. Initial treatment was categorized as (A) Adjuvant or definitive high-dose RT (78 Gy/39fx or 24 Gy/1fx) vs (B) surgery-only or low dose RT. The primary endpoint was the cumulative incidence of local failure.A total of 31 patients were treated from 2010 through 2020. Median age was 55 years, tumor location was 64% sacrum, 13% lumbar, 16% cervical and 6% clivus. Median tumor volume was 148 cc (8.3 cm in largest diameter), 42% of patients received curative-intent surgery and 65% received primary RT (adjuvant or definitive). 5-year cumulative incidence of local failure was 48% in group A vs 83% in group B (p = 0.041). Tumor size 330 cc was associated with local failure (SHR 2.2, 95% CI 1.12 to 7.45; p = 0.028). Eight patients developed distant metastases, with a median metastases-free survival of 56.1 months. 5-year survival for patients that received high dose RT was 72% vs 76% in patients that received no or low dose RT (p = 0.63).Our study suggests high-dose photon IG-IMRT improves local control in the initial management of chordomas. Health systems should promote reference centers with clinical expertise and technical capabilities to improve outcomes for this complex disease.

Background Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis that affects the aorta and its major branches, eventually leading to the development of aortic aneurysm and vascular stenosis or occlusion. This retrospective and prospective study aimed to investigate whether the gut dysbiosis exists in patients with TAK and to identify specific gut microorganisms related to aortic aneurysm formation/progression in TAK. Methods We analysed the faecal microbiome of 76 patients with TAK and 56 healthy controls (HCs) using 16S ribosomal RNA sequencing. We examined the relationship between the composition of the gut microbiota and clinical parameters. Results The patients with TAK showed an altered gut microbiota with a higher abundance of oral-derived bacteria, such as Streptococcus and Campylobacter, regardless of the disease activity, than HCs. This increase was significantly associated with the administration of a proton pump inhibitor used for preventing gastric ulcers in patients treated with aspirin and glucocorticoids. Among patients taking a proton pump inhibitor, Campylobacter was more frequently detected in those who underwent vascular surgeries and endovascular therapy for aortic dilatation than in those who did not. Among the genus of Campylobacter, Campylobacter gracilis in the gut microbiome was significantly associated with clinical events related to aortic aneurysm formation/worsening in patients with TAK. In a prospective analysis, patients with a gut microbiome positive for Campylobacter were significantly more likely to require interventions for aortic dilatation than those who were negative for Campylobacter. Furthermore, patients with TAK who were positive for C. gracilis by polymerase chain reaction showed a tendency to have severe aortic aneurysms. Conclusions A specific increase in oral-derived Campylobacter in the gut may be a novel predictor of aortic aneurysm formation/progression in patients with TAK.

The development of neural circuits involves wiring of neurons locally following their generation and migration, as well as establishing long-distance connections between brain regions. Studying these developmental processes in the human nervous system remains difficult because of limited access to tissue that can be maintained as functional over time in vitro. We have previously developed a method to convert human pluripotent stem cells into brain region-specific organoids that can be fused and integrated to form assembloids and study neuronal migration. In contrast to approaches that mix cell lineages in 2D cultures or engineer microchips, assembloids leverage self-organization to enable complex cell-cell interactions, circuit formation and maturation in long-term cultures. In this protocol, we describe approaches to model long-range neuronal connectivity in human brain assembloids. We present how to generate 3D spheroids resembling specific domains of the nervous system and then how to integrate them physically to allow axonal projections and synaptic assembly. In addition, we describe a series of assays including viral labeling and retrograde tracing, 3D live imaging of axon projection and optogenetics combined with calcium imaging and electrophysiological recordings to probe and manipulate the circuits in assembloids. The assays take 3-4 months to complete and require expertise in stem cell culture, imaging and electrophysiology. We anticipate that these approaches will be useful in deciphering human-specific aspects of neural circuit assembly and in modeling neurodevelopmental disorders with patient-derived cells.

Research has been continually growing toward the development of image-based structural health monitoring tools that can leverage deep learning models to automate damage detection in civil infrastructure. However, these tools are typically based on RGB images, which work well under ideal lighting conditions, but often have degrading performance in poor and low-light scenes. On the other hand, thermal images, while lacking in crispness of details, do not show the same degradation of performance in changing lighting conditions. The potential to enhance automated damage detection by fusing RGB and thermal images together within a deep learning network has yet to be explored. In this paper, RGB and thermal images are fused in a ResNET-based semantic segmentation model for vision-based inspections. A convolutional neural network is then employed to automatically identify damage defects in concrete. The model uses a thermal and RGB encoder to combine the features detected from both spectrums to improve its performance of the model, and a single decoder to predict the classes. The results suggest that this RGB-thermal fusion network outperforms the RGB-only network in the detection of cracks using the Intersection Over Union (IOU) performance metric. The RGB-thermal fusion model not only detected damage at a higher performance rate, but it also performed much better in differentiating the types of damage.

Previous studies have demonstrated that a picture-drawing task can be an indicator of the affiliation children have with their peers. When a child draws himself/herself along with a peer, the distance between them is assumed to represent the extent of the affiliation held by the child toward the peer: the shorter the distance is, the more affiliation the child has. However, some issues remain before the picture-drawing task is established as a way to measure children’s affiliation, including the possibility that the instructions might bias the children's responses (Thomas & Gray, 1992), and inconsistency over where to measure in the children’s drawings (e.g., Song et al., 2015). In this study, we focused on the above two issues and addressed whether the picture-drawing task can be used for measuring children’s affiliation toward peers. We conducted our study in Japanese nursery schools with 3- to 6-year-old children (N = 676), who drew pictures of themselves and a classmate. Teachers rated how much the children had played with the drawn peer. We found that the more a child had an affiliative relationship with a peer, the shorter the distance between the drawn child and peer was when measuring the closest points and the center between the two drawn figures. Our research sheds light on the validity of the picture-drawing task for measuring children’s affiliation.

Manual visual inspection is the most common means of assessing the condition of civil infrastructure in the United States, but can be exceedingly laborious, time-consuming, and dangerous. Research has focused on automating parts of the inspection process using unmanned aerial vehicles for image acquisition, followed by deep learning techniques for damage identification. Existing deep learning methods and datasets for inspections have typically been developed for a single damage type. However, most guidelines for inspections require the identification of multiple damage types and describe evaluating the significance of the damage based on the associated material type. Thus, the identification of material type is important in understanding the meaning of the identified damage. Training separate networks for the tasks of material and damage identification fails to incorporate this intrinsic interdependence between them. We hypothesize that a network that incorporates such interdependence directly will have a better accuracy in material and damage identification. To this end, a deep neural network, termed the material-and-damage-network (MaDnet), is proposed to simultaneously identify material type (concrete, steel, asphalt), as well as fine (cracks, exposed rebar) and coarse (spalling, corrosion) structural damage. In this approach, semantic segmentation (i.e., assignment of each pixel in the image with a material and damage label) is employed, where the interdependence between material and damage is incorporated through shared filters learned through multi-objective optimization. A new dataset with pixel-level labels identifying the material and damage type is developed and made available to the research community. Finally, the dataset is used to evaluate MaDnet and demonstrate the improvement in pixel accuracy over employing independent networks.

Oxygen is a key regulator of both development and homeostasis. To study the role of oxygen, a variety of in vitro and ex vivo cell and tissue models have been used in biomedical research. However, because of ambiguity surrounding the level of oxygen that cells experience in vivo, the cellular pathway related to oxygenation state and hypoxia have been inadequately studied in many of these models. Here, we devised a method to determine the oxygen tension in bone marrow monocytes using two-photon phosphorescence lifetime imaging microscopy with the cell-penetrating phosphorescent probe, BTPDM1. Phosphorescence lifetime imaging revealed the physiological level of oxygen tension in monocytes to be 5.3% in live mice exposed to normal air. When the mice inhaled hypoxic air, the level of oxygen tension in bone marrow monocytes decreased to 2.4%. By performing in vitro cell culture experiment within the physiological range of oxygen tension, hypoxia changed the molecular phenotype of monocytes, leading to enhanced the expression of CD169 and CD206, which are markers of a unique subset of macrophages in bone marrow, osteal macrophages. This current study enables the determination of the physiological range of oxygen tension in bone marrow with spatial resolution at a cellular level and application of this information on oxygen tension in vivo to in vitro assays. Quantifying oxygen tension in tissues can provide invaluable information on metabolism under physiological and pathophyisological conditions. This method will open new avenues for research on oxygen biology.

Background While gait speed, one-leg standing balance, and handgrip strength have been shown to be independent predictors for functional disability, it is unclear whether such simple measures of physical function contribute to improved risk prediction of functional disability in older adults. Methods A total of 1,591 adults aged ≥ 65 years and without functional disability at baseline were followed up for up to 7.9 years. Functional disability was identified using the database of Japan’s Long-term Care Insurance System. Maximum gait speed, one-leg standing time, and handgrip strength were measured at baseline. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of physical function and functional disability incidence. The incremental predictive value of each physical function measure for risk prediction was quantified using the difference in overall C-statistic, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI) index. Results During follow-up (median: 7.8 years), functional disability was identified in 384 participants. All of the physical function measures were inversely associated with the risk of functional disability, independent of potential confounding factors. The multivariable adjusted HRs (95 % CIs) for functional disability per one standard deviation increment of maximum gait speed, one-leg-standing time, and hand grip strength were 0.73 (0.65–0.83), 0.68 (0.59–0.79), and 0.72 (0.59–0.86), respectively. Incorporation of each of maximum gait speed, one-leg-stand time, and hand grip strength into a basic model with other risk factors significantly improved C-statistic from 0.770 (95 % CIs, 0.751–0.794) to 0.778 (0.759–0.803), 0.782 (0.760–0.805), and 0.775 (0.756–0.800), respectively (all p Conclusions Adding any of the three measures to a basic model with other known risk factors significantly improved the prediction of functional disability and addition of all three measures provided further improvement of the prediction in older Japanese adults. These data provide robust evidence to support the practical utility of incorporating these simple physical function measures into functional disability risk prediction tools.

To examine the association between physical frailty and risk of needing long-term care, and compare the predictive value and clinical usefulness of a simple frailty scale (FRAIL) with that of the original Cardiovascular Health Study (CHS) criteria. A 6-year prospective cohort study of community-dwelling older adults in a west Japanese suburban town. 1,554 older adults aged 65 years and over who were initially free of long-term care needs at baseline. Physical frailty was defined by the CHS criteria and the FRAIL scale. The onset of needing long-term care was ascertained using national records of certification of long-term care needs. Cox proportional hazard models were used to estimate the association between physical frailty and risk of needing long-term care. Decision curve analysis was performed to compare the clinical usefulness of the two physical frailty criteria. During a median follow-up of 5.8 years, 244 were ascertained as needing long-term care. Baseline physical frailty was significantly associated with elevated risk of needing long-term care, with a multivariable-adjusted hazard ratio (HR) of 2.00 (95% confidence interval [CI], 1.32–3.02) for being frail and 1.50 (95% CI, 1.10–2.03) for being pre-frail as defined by the CHS criteria, compared with being robust (p for trend = 0.001). Similar results were found for physical frailty defined by the FRAIL scale, with a multivariable-adjusted HR (95% CIs) of 2.11 (1.25–3.56) for being frail and 1.73 (1.28–2.35) for being pre-frail vs. being robust (p for trend < 0.001). The two physical frailty criteria had similar net benefits in identifying individuals at high risk for needing long-term care. Physical frailty is significantly associated with an increased risk of needing long-term care in community-dwelling older adults in Japan. Compared with the original CHS criteria, the simple FRAIL scale has comparable predictive value and clinical usefulness for identifying individuals at risk for needing long-term care.

Quality and throughput of laser material processing are influenced by multiple laser parameters as well as material properties. Since material degradation due to laser processing is generally related to heat-affected zone, quick optimization and realization of nonthermal process is one of the most important issues for higher-grade laser processing. In this work, we developed various parameter-controlled ultrashort pulse laser system that can control various laser parameters over a wide range, such as pulse duration over three orders of magnitude. Using this laser system (wavelength: 1033 nm, pulse duration: 0.4 to 400 ps, repetition: up to 1 MHz), we have investigated nonthermal–thermal processing boundary in drilling of ceramics: aluminum nitride (AlN) and yttria-stabilized zirconia (YSZ), with high and low thermal conductivity, respectively. As a result, the AlN ceramic exhibited strong dependence of ablation rate on fluence: low-, mid- and high-fluence regimes appeared with different logarithmic correlations. Further, the nonthermal–thermal process boundaries appeared, depending on the pulse duration. On the other hand, the ablation behavior of YSZ was much different from AlN; the ablation rate did not show distinct three regimes. Further, there were no nonthermal process windows for the YSZ. Therefore, the nonthermal–thermal process boundaries were governed by the laser parameters like pulse duration as well as the material thermal conductivity.

We demonstrate that assimilation of water temperature measurements by sea turtles into an operational ocean nowcast/forecast system improves representation of mesoscale eddies and front variations in the Kuroshio-Oyashio Confluence region. For a period from August to December in 2009, vertical ranges of the measurements by six turtles covered from surface to maximum 150 m depth, and the number of the measurements in the region was comparable to that of usual sampling by research vehicles and profiling floats. Comparison of the turtle measurements and products of an operational ocean nowcast/forecast system JCOPE2M elucidated low-temperature bias in JCOPE2M due to assimilation of high-resolution satellite sea surface temperature data. Additional assimilation of the turtle data into a modified JCOPE2M system with correction of the low-temperature bias led to reasonable modification of horizontal temperature/salinity gradient associated with northward moving warm core rings separating from the Kuroshio Extension and southward moving the Oyashio water intrusion branches. Effects of the turtle data assimilation propagated to far east of the Kuroshio-Oyashio confluence region along the subarctic boundary and front through advection. Another experiment assimilating the in situ profile data excluding the traditional temperature/salinity profiles data but including only the turtle data showed that the turtle measurements captured the warm core rings better than the Oyashio intrusion branches, suggesting possible optimum design of future ocean observing systems composed of different kinds of animals and/or autonomous underwater vehicles.

A case of acquired hemophilia A (AHA) that developed in a patient with autoimmune pancreatitis (AIP) is presented. A 64-year-old woman was diagnosed with AIP in 2007. The symptoms resolved with prednisolone (PSL). Although the dose of PSL was tapered to 7.5 mg/day for maintenance, serum IgG4 levels remained high. She suddenly presented with subcutaneous bleeding in 2015. Her activated partial thromboplastin time was prolonged (80.0 s). A mixing test showed an inhibitor pattern, factor VIII (FVIII) activity was less than 1%, and FVIII inhibitor was 290 BU/mL. She was diagnosed with AHA. Her serum IgG4 was elevated to 133 mg/dL. She was treated first with PSL alone, but she developed bladder tamponade. Cyclophosphamide and activated prothrombin complex concentrate were combined with PSL. She then achieved hemostasis, and FVIII inhibitor disappeared. FVIII inhibitor had been detected since PSL was tapered and AHA recurred two months later. An enzyme-linked immunosorbent assay showed that the inhibitor was mainly IgG4 and IgG1. This case suggests that elevation of IgG4 may be associated with the development of both AHA and AIP.

To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. A prospective population-based study in a west Japanese suburban town, with two-year follow-up. Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson’s disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.

The “Caddisfly Watch” program proposes the use of larvae of the caddisfly genus Stenopsyche (Trichoptera: Stenopsychidae) to monitor the radioactive cesium (137Cs) pollution, including that of suspended solids, in river environments, as a simple method was essential for this following the Fukushima nuclear disaster in March 2011. A variety of aquatic organisms were collected from rivers in Japan in 2012 and their levels of radioactive Cs measured. Amongst all the organisms collected, the highest concentrations of 137Cs were observed in caddisfly larvae. These larvae occur at a high density and can be collected at regular intervals in most rivers throughout Japan. It is proposed that caddisfly larvae can be used as bioindicators of radioactive Cs contamination in rivers, as their temporal and spatial changes are easily assessed.

Green turtles in year-round neritic foraging habitats are widely considered to have small home ranges and to mainly feed on plant-based diets. In contrast, few studies have examined the summer-restricted habitats to which these turtles seasonally migrate. In this study, we investigated the foraging habits of green turtles migrating to the Sanriku Coast, a summer-restricted foraging habitat in a temperate area (38–39°N) of the northwest Pacific Ocean, using stable isotope analysis and biologging experiments from 2007 to 2015. Stable isotope analysis (n = 40, straight carapace length (SCL): 36.8–90.9 cm) indicated that most of the turtles, especially all smaller turtles (n = 35, SCL

Endangered loggerhead turtles (Caretta caretta) are highly migratory marine reptiles that spend extended maturation periods at sea. Although an understanding of the biology and ecology of juveniles is essential for effective conservation of this species, such information is still limited, especially for the North Pacific population. The first quantitative bycatch survey in northern Japan revealed that the Sanriku coastal area served as an important summer foraging habitat for large juvenile loggerhead turtles in the western North Pacific. To examine their year-round distribution and diving behaviour, we deployed satellite-relayed data loggers on six turtles (mean SCLn–t ± SD = 69.2 ± 9.2 cm, range = 58.3–82.5 cm). While turtles predominantly utilize the Sanriku coastal area and surrounding oceanic waters during summer, all turtles spent most of their time travelling in oceanic waters (>200 m) several kilometres east of Japan and sometimes in association with the Kuroshio Extension Current during winter. Although water temperature experienced by turtles significantly decreased during winter, they predominantly stayed in water >15 °C. There was no strong seasonal pattern in diving behaviour, and daily average dive duration was 20.9 ± 11.6 min regardless of summer or winter. In addition, turtles sporadically performed deep dives, including the deepest dive (>340 m) ever recorded for this species, during winter. These results suggest that juveniles remained active and possibly foraging in oceanic habitats throughout the winter rather than adopting the quiescent overwintering strategy (i.e. undertaking prolonged dives lasting >300 min) previously reported in adult females.

The medial meniscus is a secondary stabilizer of anterior tibial translation in anterior cruciate ligament (ACL)-deficient knees. ACL reconstruction effectively restores an increased anterior tibial translation in the ACL-deficient knee. However, knee osteoarthritis sometimes develops in ACL-reconstructed patients during a long-term follow-up period. We hypothesized that the medial meniscal position would be different between the ACL-deficient and reconstructed knees. The aim of this study was to investigate pre-operative and postoperative location of the medial meniscus in patients who underwent ACL reconstruction. ACL-reconstructed knees (28 knees) and normal knees (27 knees) were investigated. Medial tibial plateau length (MTPL) and medial tibial plateau width (MTPW) were determined using radiographic images. Magnetic resonance imaging (MRI)-based medial meniscal length (MML), medial meniscal width (MMW), and medial meniscal extrusion (MME) were measured. Postoperative change in the MML, MMW, and MME were evaluated and compared with those in normal knees. No significant differences between the ACL-deficient (pre-operative) and normal groups were noted. The ACL-reconstructed (postoperative) group showed an increase in the MML, in the percentage of the MML (%MML = 100 MML/MTPL), and in the MME. Significant differences between postoperative and normal groups were observed in the MML, %MML, and MME. MMW and MMW percentage (100 MMW/MTPW) were similar in all groups. The anteroposterior length and radial extrusion of the medial meniscus increased after ACL reconstruction. Transposition of the medial meniscus may be a possible cause of developing further degenerative knee joint disorders after ACL reconstruction.

The evolutional process of disease-associated autoantibodies in systemic lupus erythematosus (SLE) remains to be established. Here we show intraclonal diversification and affinity maturation of anti-nuclear antibody (ANA)-producing B cells in SLE. We identified a panel of monoclonal ANAs recognizing nuclear antigens, such as double-stranded DNA (dsDNA) and ribonucleoproteins (RNPs) from acute SLE subjects. These ANAs had relatively few, but nonetheless critical mutations. High-throughput immunoglobulin sequencing of blood lymphocytes disclosed the existence of sizable ANA lineages shearing critical mutations intraclonally. We further focused on anti-DNA antibodies, which are capable to bind to both single-stranded (ss) and dsDNA at high affinity. Crystal structure and biochemical analysis confirmed a direct role of the mutations in the acquisition of DNA reactivity and also revealed that these anti-DNA antibodies recognized an unpaired region within DNA duplex. Our study unveils the unique properties of high-affinity anti-DNA antibodies that are generated through antigen-driven affinity maturation in acute phase of SLE.

Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy., Post-translational modifications, such as glycosylation and sialylation, are thought to confer disease modifying effects on autoimmune-associated antibodies, including anti-citrullinated protein antibodies in rheumatoid arthritis. Here the authors show that sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis in mice.

Mechanism of zinc iron removal by zero-valent iron was discussed through zinc removal responses to several operational conditions of a packed column reactor with zero-valent iron powder. The adsorption isotherm observed implied that a kind of chemisorption was responsible for zinc removal. Zinc removal by zero-valent iron was enhanced by dissolved oxygen and ferric ion addition. However, it was deteriorated under acidic pH. In addition, zinc adsorbed on zero-valent iron was eluted by a reducing agent such as citric acid, whereas the zinc was not eluted by diluted sulfuric acid. Consequently, the zinc removal mechanism by zero-valent iron was inferred to be as follows: Zero-valent iron was firstly corroded and oxidized into ferric ion by dissolved oxygen. The ferric ion was precipitated as iron hydroxide onto the surface of the zero-valent iron powder. Zinc ion was adsorbed on and/or coprecipitated with the iron hydroxide. The iron hydroxide was finally oxidized and transformed into iron oxides.

The well-controlled fabrication of microtrenches including inclined features using normal incidence with gradual shifting of the irradiated area was demonstrated. Based on the variation of trench width depending on the laser fluence, the existence of gaps between the edge of the irradiated area and sidewall of the trench was shown. Because of these gaps, the shifted laser pulse can stay at the bottom of the trenches in the fabrication of the inclined features. In laser-induced backside wet etching (LIBWE), the photo-activated region generated within organic solution would act on the glass surface and results in etching. It was indicated that the photo-activated region generated at the bottom of the trenches acted not only on the bottom of the trench but also on the sidewalls. Based on such etching of the sidewall, fabrication of inclined features becomes possible. In this method, the tilting angle can be changed within one deep trench. Flexible structure formation deep inside the silica glass can be achieved.

Magnetic resonance imaging (MRI) is one of the most promising techniques for the non-invasive visualization of biomarkers and biologically relevant species, both in vivo and ex vivo. Although (1)H MRI with paramagnetic contrast agents, such as Gd(3+) complexes and iron oxide, is widely used, it often suffers from low contrast because of the large background signals caused by the abundant distribution of protons in biological samples. Here we report the use of supramolecular organic nanoparticles to detect specific proteins by (19)F-based MRI in an off/on mode. In NMR spectroscopy these designed probes are silent when aggregated, but in the presence of a target protein they disassemble to produce a sharp signal. This 'turn-on' response allowed us to visualize clearly the protein within live cells by (19)F MRI and construct an in-cell inhibitor assay. This recognition-driven disassembly of nanoprobes for a turn-on (19)F signal is unprecedented and may extend the use of (19)F MRI for specific protein imaging.

An automotive component (steering helical gear) made from low-alloy structural steel SCr420H was gas-carburized and oil-quenched. Axial contraction of total length was measured after such case-hardening process. Using DEFORM-HT Ver 6.1 simulation tool incorporating phase transformation kinetics, the causal factor of negative axial distortion is studied. Analysis of time-dependent displacement, temperature, phase transformation, and stress-strain generation is presented. Total strain and individual strain (e.g., thermal, elastic, plastic, phase transformation, and transformation plasticity strain) are included. Three simulations consisting of case hardening with transformation plasticity (TP), case hardening without TP, and through hardening with TP were conducted to asses the influence of transformation plasticity and martensite as well as retained austenite in contributing the axial contraction of total length. Finally, transformation plasticity has a greater influence than volume fraction of martensite and retained austenite in producing the negative axial distortion.