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Abstract Background Microfracture is a surgical technique that involves creating multiple holes of 3–4 mm depth in the subchondral bone to recruit stem cells in the bone marrow to the lesion, inducing fibrocartilage repair and knee cartilage regeneration. Recently, it has been reported that increasing the exposed area of the lower cartilaginous bone (drilling a lot of holes) increases the outflow of stem cells, which is expected to affect the physical properties of the subchondral bone when the exposed area is large. The purpose of this study was to analyse the effect of the distance between the holes in the microfracture procedure on the structural stability of the osteochondral bone using a finite element method. Methods In this study, lateral aspects of the femoral knee, which were removed during total knee arthroplasty were photographed using microtomography. The model was implemented using a solitary walks program, which is a three-dimensional simplified geometric representation based on the basic microtomography data. A microfracture model was created by drilling 4 mm-deep holes at 1, 1.5, 2, 2.5, 3, 4, and 5 mm intervals in a simplified three-dimensional (3D) geometric femoral model. The structural stability of these models was analysed with the ABAQUS program. We compared the finite element model (FEM) based on the microtomography image and the simplified geometric finite element model. Results Von Mises stress of the subchondral bone plate barely increased, even when the distance between holes was set to 1 mm. Altering the distance between the holes had little impact on the structural stability of the subchondral bone plate. Safety factors were all below 1. Conclusions Although we did not confirm an optimal distance between holes, this study does provide reference data and an epidemiological basis for determining the optimal distance between the holes used in the microfracture procedure.

Abstract Background On September 27, 2012, at 3:43 pm, a hydrogen fluoride spill occurred in a manufacturing plant located at the 4th complex of the Gumi National Industrial Complex in Gumi City, South Korea. The present study aimed to evaluate the psychological effects of the hydrogen fluoride spill on the members of the community and to investigate their relationships with physical symptoms and changes in psychological effects occurring as time passed after the accident. Methods The 1st phase involved a survey of 1359 individuals that was conducted 1 month after the spill, and the 2nd phase involved a survey of 711 individuals that was conducted 7 months after the accident. The questionnaires included items for assessing demographic characteristics, hydrogen fluoride exposure level, physical symptoms, and psychological status. Physical symptoms were assessed to determine the persistence of irritations. Psychological status was assessed to investigate the impact of event level using the Impact of Event Scale – Revised Korean version (IES-R-K), and the anxiety level was assessed using the Beck Anxiety Inventory (BAI). Results As the hydrogen fluoride exposure level increased, the impact of event and anxiety levels increased significantly both 1 and 7 months after the accident (p

Abstract This study aimed to investigate the effect of patient engagement in self-monitoring with a telemonitoring device on glycemic control among patients with type 2 diabetes. We conducted a subanalysis of the telemonitoring device study in Kaiser Permanente Northern California members. We divided the telemonitoring group into 53 frequent and 54 infrequent users based on self-monitoring of blood glucose (SMBG) frequency of the first 6 weeks. The frequency of SMBG transmitted from the telemonitoring device was examined over 24 weeks. Clinic and laboratory tests were collected at baseline, 6 weeks and 6 months. There was no significant difference in baseline HbA1c level between the two groups. After 6 months, change in HbA1c was −2.4 ± 1.6% among frequent users and −1.5 ± 1.5% among infrequent users (p = 0.003). The proportion of patients achieving target HbA1C level at 6 months was significantly higher among frequent users than among infrequent users. An increased frequency of SMBG was significantly correlated with a reduction in HbA1c at 6 months. In conclusion, initial active engagement in self-monitoring with a telemonitoring device could provide incremental improvement of glycemic control over 6 months.

BackgroundDiabetes self-management education and reinforcement are important for effective management of the disease. We investigated the effectiveness of interactive small-group education on glycemic, blood pressure, and lipid levels.MethodsFor this study, 207 type 2 diabetes patients with suboptimal glycemic control (HbA1c levels >6.5%) were enrolled. The conventional education group received an existing education program from April to November in 2006, and the interactive education group received a new small-group education program from December 2006 to July 2007. The two groups were comparatively analyzed for changes in blood sugar, glycated hemoglobin, lipid, and blood pressure at baseline, 3, 6, and 12 months and the proportion of patients achieving target goals at 12 months.ResultsAfter 12 months of follow-up, HbA1c levels in the interactive education group were significantly lower than in the conventional education group (6.7% vs. 6.4%, P

BackgroundWe performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA) indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention.MethodsFrom 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, %) was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%), stable weight (-5.0 to 5.0%), weight gain (≥5.0%). Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes.ResultsProgressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR) in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression.ConclusionIncreased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.

Nucleoplasmic complexes composed of phospholipids, IP3R/Ca(super 2+) channels and Ca (super 2+) storage protein chromogranin (CGB) are studied by 3D image reconstruction and numerous vesicular structures interspersed between the heterochromatins are observed. Examinations reveal that these vesicles are the IP3-sensitive nucleoplasmic Ca(super 2+) stores that store large amounts of calcium that can be released in response to inositol 1,4,5-triphosphate.

The potential contribution of chromogranin B (CGB) on IP(sub 3-)dependent Ca(super 2+) mobilization in the nucleas is investigated using both neuroendorcrine PC12 and nonneuroendorcine NIH3T3 cells. The results highlight critical contribution of CGB in the IP(sub 3-)induced Ca(super 2+) release in the nucleus.

Purified native form of secretogranin II, from bovine adrenal medullary chromaffin cell secretory granules, predominantly exhibits beta-sheet and random coil structures with low level of alpha-helicity. Data indicate that it undergoes a pH-dependent conformational change, acidic pH-, and calcium-dependent aggregation. Furthermore, secretogranin II participates in the biogenesis of secretory granules.

The specific part of chromogranin A (CGA) which is involved in oligomerization is determined by preparing 14 peptides, to signify different parts of the CGA. Analytical ultracentrifugation is used to study the character of oligomerization in the peptides. The conserved C-terminal area, which is signified by peptide 14, shows dimerization and tetramerization characteristics resembling those of whole CGA. This region alone shows oligomerization. The tetramerization of the peptide shows large delta S degree values, despite the minute size of the peptide.

The soluble parts of the vesicular proteins reveal the occurrence of chromogranin A, a Ca2+ binding protein with low-affinity and high capacity, which monitors the Ca2+ buffering role of secretory vesicles. High levels of pH separate chromogranin A from the secretory vesicle membrane and low levels of pH bind the membrane to chromogranin A. The intravesicular side of the membrane shows the reaction of chromogranin A on the protein components. The vesicle membrane binds to the N-terminal area of chromogranin A in a process which is dependent on pH.

Binding of chromogranin A (CGA) to calmodulin (CaM) was examined through quantitative analysis of the intrinsic tryptophan fluorescence with and without Ca2+. The binding interaction of CGA to CaM was found to be exclusively dependent on the presence of Ca2+. Various CGA peptides that represented several segments of CGA were synthesized and the ability of each peptide to bind CaM were analyzed by affinity chromatography and fluorescence spectroscopy. Analysis of the amino acid sequence of CGA identified three possible CaM-binding sites.

Electronic and optical properties of non-trivial semipolar AlInGaN/InGaN quantum well (QW) structures are investigated by using the multiband effective-mass theory and non-Markovian optical model. On vicinal c-plane GaN substrate miscut by a small angle (θ<40°) from c-plane, the AlInGaN/InGaN system is shown to have ~3 times larger spontaneous emission peak intensity than the conventional InGaN/GaN system at green wavelength. It is attributed to much larger optical matrix element of the quaternary AlInGaN/InGaN system, derived from the reduction of internal electric field induced by polarizations. This effect exceeds the performance-degrading factor of smaller quasi-Fermi-level separation for the quaternary AlInGaN/InGaN system than that for the conventional InGaN/GaN system. Results indicate that the use of quaternary III-nitride QWs on vicinal substrates may be beneficial in improving the performance of optical devices emitting green light. [ABSTRACT FROM AUTHOR]

Slicing 3D polygonal meshes is a fundamental operation in various applications such as virtual surgery, garment simulation, and game development. Existing methods primarily slice meshes using either a single line or a set of line segments approximating a smooth curve. This paper introduces a novel approach to freely slice a triangle mesh using a freeform curve without discretizing it into line segments. The user draws a stroke on the screen, defining the desired cutting trajectory. Subsequently, a freeform curve approximating this stroke is generated and extended into a ruled surface in the user’s viewing direction. To efficiently compute intersections between the ruled surface and a triangle mesh, the Line–Surface Intersection (LSI) problem is broken down into two subproblems: Plane–Curve Intersection (PCI) followed by Line–Line Intersection (LLI). Intersection points are then connected to form polylines, effectively cutting the mesh into multiple submeshes. To ensure the solidity of the submeshes, cross-sections are generated by trimming the ruled surface along the polylines and merged with the corresponding submeshes. Our method empowers users to slice triangle meshes along arbitrary trajectories encompassing both straight and freely curved paths while preserving efficiency and accuracy. The effectiveness of the proposed approach is demonstrated through experimental results showing various examples of mesh slicing.

Neurofeedback can be utilized to treat various neuropsychiatric disorders in children. However, therapists primarily set threshold values for neurofeedback training. Thus, the training effect becomes subjective owing to the experience of the therapist. A clinically inexperienced therapist could set inappropriate thresholds, rendering the training ineffective. In this study, an effective neurofeedback system that includes signal processing of large amount of electroencephalogram (EEG) data and auto thresholding and provides various training contents was developed. The system uses a method that determines optimal threshold values, which are significant for an effective neurofeedback system. The success or failure of the activation and inhibition of specific EEG frequencies was determined based on these threshold values. The system determined an optimal threshold value to obtain the target success rate using a numerical optimization technique. The success or failure feedback for the reward and inhibit EEG frequencies was generated using auto thresholding. This feedback was sent to the training contents by the inter-process communication module to control the contents. Most training content was implemented as serious video games by using a commercial game engine. Success feedback on reward EEG frequency leads to game progress. By contrast, failure feedback on inhibiting EEG frequency hinders game progress. Consequently, the user gains the self-regulation ability to enhance the reward EEG frequency and suppress the inhibit EEG frequency. A pilot study involving five children with attention deficiency was conducted to demonstrate the effectiveness of the developed system. The results demonstrated that the childrent’s attention improved after neurofeedback training.

Objectives: To identify and estimate the non-point source (NPS) pollution loads in the Yongdam watershed, and to take an appropriate NPS management plan suitable for the environmental conditions of the sub-basin of Yongdam watershed. Methods: The NPS pollutant loads of the Yongdam watershed was investigated to establish the hydrological simulation program-fortran (HSPF) model for the study area so that the characteristics of non-point runoff were simulated. Furthermore, the detailed catchment area subject to non-point pollution management was selected and the effect of reducing non-point pollution was examined based on the various simulation results. Results and Discussion: The three sub-basins, including specific component of catchments, of Yongdam watershed was selected according to the load intensity and distribution of NPS pollution. The result of analyzing the load flowing into the downstream by rainfall intensity revealed that the pollutant load accounted for 11.8~19.9% in the dry season, and for Jinan-cheon sub-basin the load was high in the range of 10~30 mm while Janggye-cheon sub-basin and downstream of Janggye-cheon junction sub-basin showed a high load in the range 30~60 mm. In addition, the load duration curve (LDC) showed the excess frequency of BOD load was high when the flow rate increased at the end of stream for each sub-basin, whereas the load excess frequency was high in T-P in the entire flow range. LDC analysis led to us that the water quality of stream was affected by point and non-point pollutants in a complex way. When NPS pollution reduction facilities were installed by selecting 10 detailed catchments with high need for NPS pollution management, the reduction of T-P load was estimated to be reduced by 1.85 kg/d in Jinan-cheon sub-basin, 6.40 kg/d in Janggye-cheon sub-basin, and 6.58 kg/d in downstream of Janggye-cheon junction sub-basin. Conclusions: Through various simulation experiments using the HSPF model, it was feasible to select an catchment subject to NPS pollution control in detail and evaluate the effect of reducing NPS pollution.

Due to the outbreak of the SARS-CoV-2 virus, drug repurposing and Emergency Use Authorization have been proposed to treat the coronavirus disease 2019 (COVID-19) during the pandemic. While the efficiency of the drugs has been discussed, it was identified that certain compounds, such as chloroquine and hydroxychloroquine, cause QT interval prolongation and potential cardiotoxic effects. Drug-induced cardiotoxicity and QT prolongation may lead to life-threatening arrhythmias such as torsades de pointes (TdP), a potentially fatal arrhythmic symptom. Here, we evaluated the risk of repurposed pyronaridine or artesunate-mediated cardiac arrhythmias alone and in combination for COVID-19 treatment through in vitro and in silico investigations using the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The potential effects of each drug or in combinations on cardiac action potential (AP) and ion channels were explored using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and Chinese hamster ovary (CHO) cells transiently expressing cardiac ion channels (Nav1.5, Cav1.2, and hERG). We also performed in silico computer simulation using the optimized O’Hara-Rudy human ventricular myocyte model (ORd model) to classify TdP risk. Artesunate and dihydroartemisinin (DHA), the active metabolite of artesunate, are classified as a low risk of inducing TdP based on the torsade metric score (TMS). Moreover, artesunate does not significantly affect the cardiac APs of hiPSC-CMs even at concentrations up to 100 times the maximum serum concentration (Cmax). DHA modestly prolonged at APD90 (10.16%) at 100 times the Cmax. When considering Cmax, pyronaridine, and the combination of both drugs (pyronaridine and artesunate) are classified as having an intermediate risk of inducing TdP. However, when considering the unbound concentration (the free fraction not bound to carrier proteins or other tissues inducing pharmacological activity), both drugs are classified as having a low risk of inducing TdP. In summary, pyronaridine, artesunate, and a combination of both drugs have been confirmed to pose a low proarrhythmogenic risk at therapeutic and supratherapeutic (up to 4 times) free Cmax. Additionally, the CiPA initiative may be suitable for regulatory use and provide novel insights for evaluating drug-induced cardiotoxicity.

The presence and localization of secretogranin II in nucleoplasmic [Ca.sup.2+] store vesicles are studied. Secretogranin II is found to facilitate the storage and control of [Ca.sup.2+] in the nucleus.

The nuclear inositol 1,4,5-triphosphate receptor (I[P.sub.3]R)/[Ca.sup.2+] channels are more sensitive to I[P.sub.3] than cytoplasmic one in both neuroendocrine PC12 cells and nonneuroendocrine NIH3T3 cells. The high I[P.sub.3] sensitivity has reflected the physiological roles of secretory cells, given that secretion is the major function of secretory cells and is under a tight control of intracellular [Ca.sup.2+] concentrations.

The presence of a nucleoplasmic complex composed of the inositol 1,4,5-trisphosphate receptor (IP3R), Ca(super 2+), chromogranin B, and phospholipids is found with an estimated molecular mass of ~2-3 x 10(super 7) Da. The results suggest the possibility of the presence of an IP3R-sensitive Ca(super 2+) store in the nucleoplasm.

The number of secretory granules and the extent of IP3-mediated intracellular Ca(super 2+) mobilization in the cells are measured. The relationship between the number of secretory granules and the magnitude of Ca(super 2+) mobilization are investigated.

Objectives To evaluate the difference between healthcare professionals (HCPs) and adults with spinal cord injury (SCI) in Asia regarding knowledge and interpretation of ‘exercise intensity’ for aerobic exercise prescription.Methods and study design A survey was distributed to practising HCP and adults with SCI. It was completed in participants’ local language on topics related to the importance of exercise frequency, intensity, time and type; methods for monitoring and terms related to exercise intensity prescription. χ2 analysis was used to detect differences in HCP or those with SCI.Results 121 HCP and 107 adults with an SCI ≥1 years (C1–L4) participated. Responses revealed 61% of all HCP ranked ‘intensity’ being most important whereas only 38% respondents from the SCI group ranked it as high importance (p=0.008). For those with SCI, ‘frequency’ was most important (61%) which was significantly higher than the 45% selected by HCPs (p=0.030). Of the 228 respondents on average only 34% believed that the terms, ‘moderate’ and ‘vigorous’ provided enough information for aerobic exercise intensity prescription. HCP most often used HR methods compared with the SCI group (90% vs 54%; p

Abstract Background Dyspnea is a common symptom in patients presenting to the emergency department. It has a variety of causes that range from non-urgent to life-threatening. One episode of dyspnea in a healthy young person is easy to overlook. However, if the symptoms occur after physically or emotionally stressful events, careful evaluation needs to be undertaken because it may be associated with Takotsubo syndrome, which is rarely expected but can be fatal. Herein, we report the case of Takotsubo syndrome in a healthy young woman who arrived at the emergency department after experiencing a short single episode of dyspnea following a minor surgery. Case presentation A 23-year old woman with no underlying chronic disease underwent closed reduction surgery for a nasal bone fracture under general anesthesia (with sevoflurane as the anesthetic). Approximately 5 h later, she presented to the emergency department with dyspnea, which improved soon upon arrival at the emergency department. There were no other symptoms. The dyspnea occurred about 5 h after being discharged on observation, with an uneventful postoperative course. Her electrocardiogram and chest X-ray findings were unremarkable. On testing, troponin I and creatine kinase myocardial band levels were elevated at 6.122 ng/mL and 11.2 µg/L (reference ranges: 0.000–0.046 ng/mL and 0.0–5.0 µg/L), respectively. Bedside echocardiography revealed an ejection fraction of 25%, with mid-ventricular and apical akinesia and basal hyperkinesia. The pulmonary and coronary angiographic computed tomographic scans were unremarkable. Hence, apical Takotsubo syndrome was suspected. A follow-up echocardiogram taken 5 days after admission showed full recovery with a normalized ejection fraction (60%) and no regional wall motion abnormality. The patient was discharged on the sixth day with no other complications. Conclusion When atypical symptoms, such as transient dyspnea, manifest, it becomes necessary to suspect and diagnose Takotsubo syndrome to ensure timely and appropriate medical management, especially when a preceding stressful event, such as minor surgery has occurred. It might be helpful to perform bedside point-of-care echocardiography to check for regional wall motion abnormalities that are typically associated with Takotsubo syndrome.

Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety. Methods We conducted a large-scale, multi-centre, randomized clinical trial involving 484 patients. Patients in the intervention group ( n = 244) were treated with the Internet-based system for six months, while the control group ( n = 240) received the usual outpatient management over the same period. HbA1c, blood chemistries, anthropometric parameters, and adverse events were assessed at the beginning of the study, after three months, and the end of the study. Results There were no initial significant differences between the groups with respect to demographics and clinical parameters. Upon six-month follow-up, HbA1c levels were significantly decreased from 7.86 ± 0.69% to 7.55 ± 0.86% within the intervention group ( p < 0.001) compared to 7.81 ± 0.66% to 7.70 ± 0.88% within the control group. Postprandial glucose reduction was predominant. A subgroup with baseline HbA1c higher than 8% and good compliance achieved a reduction of HbA1c by 0.8 ± 1.05%. Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age. There were no adverse events associated with the intervention. Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial. This system may be effective in improving diabetes control in the general population. [ABSTRACT FROM AUTHOR]

Objective Bilateral frozen shoulder (FS) is often treated with intra-articular corticosteroid injection (IACI). No studies have been performed to establish whether IACI must be administered in both shoulders or in only one shoulder to improve function. This study was therefore performed to determine whether unilateral IACI improves shoulder pain and passive range of motion (pROM) in bilateral FS. Methods The medical records of 165 patients with bilateral primary FS who underwent ultrasonography-guided IACI (2 mL of 10-mg/mL triamcinolone acetonide mixed with 5 mL of 1% lidocaine) in one shoulder were retrospectively reviewed. The outcome measures, namely the numeric rating scale (NRS) scores and pROM values (abduction, external rotation, flexion, hyperextension, and internal rotation), were evaluated pre- and post-injection. Results The patients’ mean age was 54.0 ± 8.0 years. The mean symptom duration was 6.5 ± 2.8 months. The mean follow-up period after injection was 6.7 ± 0.8 weeks. The NRS scores and pROM values significantly improved in both the injected and non-injected shoulders. Conclusions This study showed that unilateral IACI in patients with bilateral FS improves the clinical outcome of the non-injected shoulder. We suggest that physicians observe the non-injected shoulder after unilateral injection rather than performing bilateral injections.

Background: The aim of this study was to identify the relationships between borderline serum liver enzyme abnormalities and the incidence of impaired fasting glucose (IFG) and diabetes mellitus (DM) during a 7-year follow-up of workers, and to evaluate the quantitative level of risks. Methods: A total of 749 workers in an electronics manufacturing company were divided into the normal fasting blood glucose (n = 633), IFG (n = 98), and DM (n = 18) groups, according to the results of their health checkup in 2006. Among 633 workers in the normal group, excluding 55 workers who were impossible to follow, incidence rate and relative risks of 578 workers to the IFG or DM in 2013 according to the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (γ-GTP) were investigated. The liver enzyme levels were categorized as A (normal), B (borderline elevation), and R (definite elevation) following the standard of the National Health Insurance Service of Korea. Results: The incidence rate of IFG or DM based on ALT level was 9.7% for the A, 30.0% for B, and 15.4% for R. According to -GTP, the incidence rate was 9.8% for A, 34.5% for B, and 25.0% for R. The relative risk(RR) to the incidence of IFG or DM depending on the level of ALT were 3.09 in B and 1.59 in R compared to A. According to -GTP, RR was 3.52 in B and 2.55 in R compared to A. AST level was not related to the incidence of IFG or DM. A multiple logistic regression analysis with the incidence of IFG or DM as a dependent variable resulted in an odds ratio of 2.664(1.214-5.849) for B level ALT, 3.685(1.405-9.667) for B level of -GTP even after adjustment for other variables such as age, sex, body mass index, AUDIT score, systolic blood pressure, and triglyceride. Conclusions: Even borderline elevations of ALT and γ-GTP, but not AST, increased the incidence and risk of IFG or DM after 7 years. Borderline elevation of ALT and γ-GTP was identified as an independent risk factor of IFG or DM. [ABSTRACT FROM AUTHOR]

A shape detail transfer is the process of extracting the geometric details of a source region and transferring it onto a target region. In this paper, we present a simple and effective method, called GeoStamp, for transferring shape details using a Poisson equation. First, the mean curvature field on a source region is computed by using the Laplace–Beltrami operator and is defined as the shape details of the source region. Subsequently, the source and target regions are parameterized on a common 2D domain, and a mean curvature field on the target region is interpolated by the correspondence between two regions. Finally, we solve the Poisson equation using the interpolated mean curvature field and the Laplacian matrix of the target region. Consequently, the mean curvature field of the target region is replaced with that of the source region, which results in the transfer of shape details from the source region to the target region. We demonstrate the effectiveness of our technique by showing several examples and also show that our method is quite useful for adding shape details to a surface patch filling a hole in a triangular mesh.

Curves on a polygonal mesh are quite useful for geometric modeling and processing such as mesh-cutting and segmentation. In this paper, an effective method for constructing C1 piecewise cubic curves on a triangular mesh M while interpolating the given mesh points is presented. The conventional Hermite interpolation method is extended such that the generated curve lies on M. For this, a geodesic vector is defined as a straightest geodesic with symmetric property on edge intersections and mesh vertices, and the related geodesic operations between points and vectors on M are defined. By combining cubic Hermite interpolation and newly devised geodesic operations, a geodesic Hermite spline curve is constructed on a triangular mesh. The method follows the basic steps of the conventional Hermite interpolation process, except that the operations between the points and vectors are replaced with the geodesic. The effectiveness of the method is demonstrated by designing several sophisticated curves on triangular meshes and applying them to various applications, such as mesh-cutting, segmentation, and simulation.

The purpose of this study was to verify the educational effects of a mandatory introductory engineering design course wherein the students find their own project items and solve them using creative projects. Case studies, investigation through surveys, and weekly reflective journals have been performed in order to achieve this goal. The results of this research present the details of running the class and the outcomes of the student's projects; the educational effects and difficulties are analyzed. It turned out that brainstorming is very helpful for idea generation and patent searches are useful in the problem solving stage. The finding of real engineering problems regarding the project topics is the most difficult part of the project, however it strongly correlates to the improvement of the students' hard skills and promotes the perception of engineering problems in the sense of engineers, not as users but as suppliers. [ABSTRACT FROM AUTHOR]

The roles of calmodulin (CaM) have been key points of controversy in the regulation of inositol-1,4,5-trisphosphate receptor (IP3R). To address the issue, we studied the interaction between CaM and the suppressor domain of IP3R, a key allosteric regulatory domain. First, by means of a pulldown and a fluorescence titration experiment, we confirmed the interaction. Through subsequent NMR binding experiments, we observed dramatic peak disappearances of the suppressor domain on interaction with apo-CaM. The data indicated that apo-CaM induces large-scale dynamic conformational changes in the suppressor domain, involving partial unfolding and subdomain rearrangement. Analysis of the NMR data of CaM surprisingly revealed that its C lobe alone can cause such changes. Further binding experiments showed that calcium allows the free N lobe to bind to the suppressor domain, which induces extra conformational changes in both of the proteins. These results were also confirmed with CaM deletion mutants with either the N or C lobe. On the basis of this novel binding mechanism, we propose a model in which the partial unfolding of the suppressor domain by apo-CaM and the stepwise binding of the N lobe of CaM to the suppressor domain are important elements of calcium/ CaM inhibition of IP3R. We believe that our working model encompasses previous regulation mechanisms of IP3R by calcium/CaM and provides new insights into the CaM-target interaction. [ABSTRACT FROM AUTHOR]

The inositol 1,4,5-trisphosphate (IP)-mediated intracellular Ca releases in secretory cells play vital roles in controlling not only the intracellular Ca concentrations but also the Ca-dependent exocytotic processes. Of intracellular organelles that release Ca in response to IP, secretory granules stand out as the most prominent organelle and are responsible for the majority of IP-dependent Ca releases in the cytoplasm of chromaffin cells. Bovine chromaffin granules were the first granules that demonstrated the IP-mediated Ca release as well as the presence of the IP receptor (IPR) in granule membranes. Secretory granules contain all three (type 1, 2, and 3) IPR isoforms, and 58-69% of total cellular IPR isoforms are expressed in bovine chromaffin granules. Moreover, secretory granules contain large amounts (2-4 mM) of chromogranins and secretogranins; chromogranins A and B, and secretogranin II being the major species. Chromogranins A and B, and secretogranin II are high-capacity, low-affinity Ca binding proteins, binding 30-93 mol of Ca/mol of protein with dissociation constants of 1.5-4.0 mM. Due to this high Ca storage properties of chromogranins secretory granules contain ~40 mM Ca. Furthermore, chromogranins A and B directly interact with the IPRs and modulate the IPR/Ca channels, i.e., increasing the open probability and the mean open time of the channels 8- to 16-fold and 9- to 42-fold, respectively. Coupled chromogranins change the IPR/Ca channels to a more ordered, release-ready state, whereby making the IPR/Ca channels significantly more sensitive to IP. [ABSTRACT FROM AUTHOR]

Background: The gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain. The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored. Principal Findings: We have therefore studied the potential existence of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes using human brain tissue samples in contrast to cultured astrocytes that had primarily been used in the past. It was thus found that secretory granule marker proteins chromogranins and secretogranin II localize in the large dense core vesicles of astrocytes, thereby confirming the large dense core vesicles as bona fide secretory granules. Moreover, consistent with the major IP3-dependent intracellular Ca2+ store role of secretory granules in secretory cells, secretory granules of astrocytes also contained all three (types 1, 2, and 3) IP3R isoforms. Significance: Given that the secretory granule marker proteins chromogranins and secretogranin II are high-capacity, lowaffinity Ca2+ storage proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+ channels, i.e., increase both the mean open time and the open probability of the channels, these results imply that secretory granules of astrocytes function as the IP3-sensitive intracellular Ca2+ store. [ABSTRACT FROM AUTHOR]

Of all the intracellular organelles, secretory granules contain by far the highest calcium concentration; secretory granules of typical neuroendocrine chromaffin cells contain ∼40 mM Ca2+ and occupy ∼20% cell volume, accounting for >60% of total cellular calcium. They also contain the majority of cellular inositol 1,4,5-trisphosphate receptors (IP3Rs) in addition to the presence of >2 mM of chromogranins A and B that function as high-capacity, low-affinity Ca2+ storage proteins. Chromogranins A and B also interact with the IP3Rs and activate the IP3R/Ca2+ channels. In experiments with both neuroendocrine PC12 and nonneuroendocrine NIH3T3 cells, in which the number of secretory granules present was changed by either suppression or induction of secretory granule formation, secretory granules were demonstrated to account for >70% of the IP3-induced Ca2+ releases in the cytoplasm. Moreover, the IP3 sensitivity of secretory granule IP3R/Ca2+ channels is at least ∼6- to 7-fold more sensitive than those of the endoplasmic reticulum, thus enabling secretory granules to release Ca2+ ahead of the endoplasmic reticulum. Further, there is a direct correlation between the number of secretory granules and the IP3 sensitivity of cytoplasmic IP3R/Ca2+ channels and the increased ratio of IP3-induced cytoplasmic Ca2+ release, highlighting the importance of secretory granules in the IP3-dependent Ca2+ signaling. Given that secretory granules are present in all secretory cells, these results presage critical roles of secretory granules in the control of cytoplasmic Ca2+ concentrations in other secretory cells [ABSTRACT FROM AUTHOR]

Chromogranins and secretogranins have traditionally been known as marker proteins of secretory granules that contain the highest concentrations of cellular calcium, reaching ∼40 mM. In addition, chromogranin B was also shown to exist in the nucleus, localizing in the putative inositol 1,4,5-trisphosphate (IP3)-sensitive nucleoplasmic Ca2+ store vesicles. Chromogranins A (CGA) and B (CGB) are high-capacity, low-affinity Ca2+ binding proteins, binding 30-90 mol of Ca2+/mol with dissociation constants (Kd) of 1.5—4 mM. Yet the Ca2+binding property of secretogranins has not been studied. Here, we show the localization of secretogranin II (SgII) in the nucleus, more specifically, in the IP3-sensitive nucleoplasmic Ca2+ store vesicles along with CGB and the IP3 receptors. We have also determined the Ca2+-binding property of SgII and found that SgII binds 61 mol of Ca2+/mol (910 nmol Ca2+/mg) with a Kd of 3.0mM at the intragranular pH 5.5 and 30 mol of Ca2+/mol (440 nmol Ca2+/mg) with a Kd of 2.2 mM at a near-physiological pH 7.5. Chromogranin B also bound 50 mol of Ca2+/mol (670 nmol Ca2+/mg) with a Kd of 3.1 mM at pH 7.5. Given the high-capacity, low-affinity Ca2+-binding property of SgII and its presence in the IP3-sensitive nucleoplasmic Ca2+ store vesicles, these results suggest that SgII may function in the storage and control of Ca2+ in the nucleus through its interaction with CGB in the nucleoplasmic vesicles. [ABSTRACT FROM AUTHOR]

Imatinib mesylate is the first molecule of targeted therapy in chronic myelogenous leukaemia inhibiting constitutively activated BCR-ABL kinase. There are no long-term follow-up studies of large sample sizes to assess the toxicity of the use of imatinib mesylate over 10 years. Several cases of hepatotoxicity, including fatal liver failure, have been associated with the long-term use of imatinib mesylate. We report here on a patient who experienced immediate dominant cholestatic damage of the liver and mild hepatocyte damage during imatinib mesylate therapy. This differs from most reports showing dominantly acute hepatitis with necrosis associated with the use of imatinib mesylate. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although the inositol 1,4,5-trisphosphate (IP3) induced nuclear Ca2+ releases have been shown to play key roles in nuclear functions, the presence and operation of the IP3-dependent Ca2+ control mechanism in the nucleoplasm have not been shown. Recently, we found the presence of a high-capacity, low-affinity Ca2+-storage protein chromogranin B (CGB) and all three IP3 receptor (IP3R) isoforms in the nucleoplasm, localizing widely in both the heterochromatin and euchromatin regions. In view of the essential role of CGB -IP3R coupling in IP3-dependent Ca2+ release in the endoplasmic reticulum, the potential coupling between CGB and the IP3Rs in the nucleoplasm was investigated. Hence, we found in the present study the presence of a nucleoplasmic complex, which is composed of the IP3R, CGB, and phospholipids, with an estimated molecular mass of ∼2—3 × 107 Da, suggesting the possibility of the presence of an IP3-sensitive Ca2+ store in the nucleoplasm. Moreover, double-labeling immunogold electron microscope studies showed the colocalization of all three IP3R isoforms with CGB to the extent that the majority of each IP3R isoform-labeling gold particles found in the nucleoplasm was literally next to the CGB-labeling gold particles. In line with the potential existence of an IP3-dependent vesicular nucleoplasmic Ca2+ store, our preliminary results indeed showed a sudden release of Ca2+ from a putative nucleoplasmic Ca2+ store in response specifically to IP3 but not to inositol 1,4-bisphosphate or inositol 1,3,4,5-tetrakisphosphate. [ABSTRACT FROM AUTHOR]

A triangular mesh obtained by scanning 3D models typically contains holes. We present an effective technique for filling a hole in a triangular mesh in geometric modeling. Simple triangulation of a hole is refined and remeshed iteratively to generate an initial patch. The generated patch is then enhanced to become a target patch by minimizing the variation of principal curvatures. In discrete approximation, this produces a third-order Laplacian system of sparse symmetric positive definite matrix, and the symmetry can efficiently be used to find the robust solutions to the given Laplacian system. Laplacian smoothing of the target patch is defined as a source patch. The shape difference between two corresponding vertices of the source and the target patches is measured in terms of Euclidean distance and curvature variation. On the basis of the shape difference and a user-specified control parameter, different blending weights are determined for each vertex, and the final patch is generated by blending two patches. We demonstrate the effectiveness of our technique by discussing several examples. The experimental results show that our technique can effectively restore salient geometric features of the original shape.

Purpose: To demonstrate the superficial hyperechoic band (SHEB) in articular cartilage by using ultrasonography (US) and to assess its correlation with histological images. Methods: In total, 47 regions of interest (ROIs) were analyzed from six tibial osteochondral specimens (OCSs) that were obtained after total knee arthroplasty. Ultrasonograms were obtained for each OCS. Then, matching histological sections from all specimens were obtained for comparison with the ultrasonograms. Two types of histological staining were used: Safranin-O stain (SO) to identify glycosaminoglycans (GAG) and Masson’s trichrome stain (MT) to identify collagen. In step 1, two observers evaluated whether there was an SHEB in each ROI. In step 2, the two observers evaluated which histological staining method correlated better with the SHEB by using the ImageJ software. Results: In step 1 of the analysis, 20 out of 47 ROIs showed an SHEB (42.6%, kappa=0.579). Step 2 showed that the SHEB correlated significantly better with the topographical variation in stainability in SO staining, indicating the GAG distribution, than with MT staining, indicating the collagen distribution (P

We present a new method for constructing a parametric blending surface that smoothly connects two triangular meshes. A user selects a subregion on each triangular mesh. The local parameterizations of two selected regions are found by using geodesic polar coordinates, and a base surface on each triangular mesh is constructed by two boundary curves on parametric domain. Finally, two base surfaces are smoothly blended for generating a blending surface. The shape of a blending surface can easily be controlled by several shape parameters or by directly manipulating surface point. We demonstrate the effectiveness of our technique by showing several modeling examples.

We propose a new tangible visualization table for intuitive and effective visualization of terrain data transferred from a remote server in real time. The shape display approximating the height field of remote terrain data is generated by linear actuators, and the corresponding texture image is projected onto the shape display. To minimize projection distortions, we present a sophisticated technique for projection mapping. Gesture-based user interfaces facilitate intuitive manipulations of visualization results. We demonstrate the effectiveness of our system by displaying and manipulating various terrain data using gesture-based interfaces.

We facilitate the editing of hierarchical B-spline curves at multiple resolutions by expressing a displacement function at each level in rotation minimizing frames (RMFs) on the curve at the next lower level. When the curve is edited at a particular level, RMFs at all the higher levels are updated, and the control points of the displacement function at each higher level are obtained from these new RMFs. This transfers details created at the current level to higher levels. Our method presents a hundred-fold faster way to reflect editing results compared to the traditional approach using Frenet frames. We demonstrate the effectiveness of our technique by showing several examples of editing curves with fine details.

An efficient surface area evaluation method is introduced by using smooth surface reconstruction for three-dimensional scanned human body data. Surface area evaluations for various body parts are compared with the results from the traditional alginate-based method, and quite high similarity between the two results is obtained. We expect that our surface area evaluation method can be an alternative to measuring surface area by the cumbersome alginate method.

PN (point-normal) triangles are cubic Bézier triangles which meet at their edges to surface a triangular mesh, but this only achieves G0 continuity. We define blending regions that span the edges shared by adjacent pairs of triangular domains and blend the corresponding Bézier triangles using a univariate blending function formulated in terms of barycentric coordinates. This produces G2 continuity across boundaries while preserving G1 continuity at vertices. The sharpness of the blends can be controlled locally by varying the extent of these blending regions. We demonstrate the effectiveness of our technique by showing several modeling examples.

Alcichthys elongatus is the only species in the genus, and this work is the first to provide a comprehensive mitogenome analysis of this species. The A. elongatus mitogenome was 16,712 bp long, with biased A + T content (52.33%), and featured thirteen protein-coding genes (PCGs), twenty-two tRNAs, two rRNAs, and the control region (D-loop). The H strand encoded twenty-eight genes (twelve PCGs, fourteen tRNA, and two rRNA) and the control region, whereas the L strand encoded the remaining nine genes (ND6 and eight tRNA). Except for COXI, which started with GTG, all PCG sequences started with ATG and ended with TAA (ND4L, ND5, COXI, ATP8) or TAG (ND1, ND6) termination codons, with some (ND2, ND3, ND4, COXII, COXIII, ATP6, Cytb) having an incomplete termination codon. Except for tRNA-serine-1 (trnS), the majority of the tRNAs exhibited characteristic cloverleaf secondary structures. Based on 13 PCGs, phylogenetic analysis placed A. elongatus in the same clade as Icelus spatula. This genomic data will be useful for species identification, phylogenetic analysis, and population genetics.

The two major proteins of secretory granules of secretory cells, chromogranins A (CGA) and B (CGB), have previously been proposed to play key roles in secretory granule biogenesis. Recently, CGA was reported to play an on/off switch role for secretory granule biogenesis. In the present study we found CGB being more effective than CGA in inducing secretory granule formation in non-neuroendocrine NIH3T3 and COS-7 cells. The mean number of dense core granules formed/cell of CGAtransfected NIH3T3 cells was 2.51, whereas that of CGBtransfected cells was 4.02, indicating the formation of 60% more granules in the CGB-transfected cells. Similarly, there were 55% more dense core granules formed in the CGB-transfected COS-7 cells than in the CGAtransfected cells. Moreover, transfection of CGA- and CGB-short interfering RNA (siRNA) into neuroendocrine PC12 cells not only decreased the amount of CGA and CGB expressed but also reduced the number of secretory granules by 41 and 78%, respectively, further suggesting the importance of CGB expression in secretory granule formation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain. The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored. PRINCIPAL FINDINGS: We have therefore studied the potential existence of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes using human brain tissue samples in contrast to cultured astrocytes that had primarily been used in the past. It was thus found that secretory granule marker proteins chromogranins and secretogranin II localize in the large dense core vesicles of astrocytes, thereby confirming the large dense core vesicles as bona fide secretory granules. Moreover, consistent with the major IP3-dependent intracellular Ca2+ store role of secretory granules in secretory cells, secretory granules of astrocytes also contained all three (types 1, 2, and 3) IP3R isoforms. SIGNIFICANCE: Given that the secretory granule marker proteins chromogranins and secretogranin II are high-capacity, low-affinity Ca2+ storage proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+ channels, i.e., increase both the mean open time and the open probability of the channels, these results imply that secretory granules of astrocytes function as the IP3-sensitive intracellular Ca2+ store.