Topological magnetic structure generation using VAE-GAN hybrid model and discriminator-driven latent sampling.

Recently, deep generative models using machine intelligence are widely utilized to investigate scientific systems by generating scientific data. In this study, we experiment with a hybrid model of a variational autoencoder (VAE) and a generative adversarial network (GAN) to generate a variety of plausible two-dimensional magnetic topological structure data. Due to the topological properties in the system, numerous and diverse metastable magnetic structures exist, and energy and topological barriers separate them. Thus, generating a variety of plausible spin structures avoiding those barrier states is a challenging problem. The VAE-GAN hybrid model can present an effective approach to this problem because it brings the advantages of both VAE's diversity and GAN's fidelity. It allows one to perform various applications including searching a desired sample from a variety of valid samples. Additionally, we perform a discriminator-driven latent sampling (DDLS) using our hybrid model to improve the quality of generated samples. We confirm that DDLS generates various plausible data with large coverage, following the topological rules of the target system.

Super-resolution of magnetic systems using deep learning.

We construct a deep neural network to enhance the resolution of spin structure images formed by spontaneous symmetry breaking in the magnetic systems. Through the deep neural network, an image is expanded to a super-resolution image and reduced to the original image size to be fitted with the input feed image. The network does not require ground truth images in the training process. Therefore, it can be applied when low-resolution images are provided as training datasets, while high-resolution images are not obtainable due to the intrinsic limitation of microscope techniques. To show the usefulness of the network, we train the network with two types of simulated magnetic structure images; one is from self-organized maze patterns made of chiral magnetic structures, and the other is from magnetic domains separated by walls that are topological defects of the system. The network successfully generates high-resolution images highly correlated with the exact solutions in both cases. To investigate the effectiveness and the differences between datasets, we study the network's noise tolerance and compare the networks' reliabilities. The network is applied with experimental data obtained by magneto-optical Kerr effect microscopy and spin-polarized low-energy electron microscopy.

Searching for the ground state of complex spin-ice systems using deep learning techniques.

Searching for the ground state of a given system is one of the most fundamental and classical questions in scientific research fields. However, when the system is complex and large, it often becomes an intractable problem; there is essentially no possibility of finding a global energy minimum state with reasonable computational resources. Recently, a novel method based on deep learning techniques was devised as an innovative optimization method to estimate the ground state. We apply this method to one of the most complicated spin-ice systems, aperiodic Penrose P3 patterns. From the results, we discover new configurations of topologically induced emergent frustrated spins, different from those previously known. Additionally, a candidate of the ground state for a still unexplored type of Penrose P3 spin-ice system is first proposed through this study. We anticipate that the capabilities of the deep learning techniques will not only improve our understanding on the physical properties of artificial spin-ice systems, but also bring about significant advances in a wide range of scientific research fields requiring computational approaches for optimization.

Optimization of physical quantities in the autoencoder latent space.

We propose a strategy for optimizing physical quantities based on exploring in the latent space of a variational autoencoder (VAE). We train a VAE model using various spin configurations formed on a two-dimensional chiral magnetic system. Three optimization algorithms are used to explore the latent space of the trained VAE. The first algorithm, the single-code modification algorithm, is designed for improving the local energetic stability of spin configurations to generate physically plausible spin states. The other two algorithms, the genetic algorithm and the stochastic algorithm, aim to optimize the global physical quantities, such as topological index, magnetization, energy, and directional correlation. The advantage of our method is that various optimization algorithms can be applied in the latent space containing the abstracted representation constructed by the trained VAE model. Our method based on latent space exploration is utilized for efficient physical quantity optimization.

Estimating the effective fields of spin configurations using a deep learning technique.

The properties of complicated magnetic domain structures induced by various spin-spin interactions in magnetic systems have been extensively investigated in recent years. To understand the statistical and dynamic properties of complex magnetic structures, it is crucial to obtain information on the effective field distribution over the structure, which is not directly provided by magnetization. In this study, we use a deep learning technique to estimate the effective fields of spin configurations. We construct a deep neural network and train it with spin configuration datasets generated by Monte Carlo simulation. We show that the trained network can successfully estimate the magnetic effective field even though we do not offer explicit Hamiltonian parameter values. The estimated effective field information is highly applicable; it is utilized to reduce noise, correct defects in the magnetization data, generate spin configurations, estimate external field responses, and interpret experimental images.

Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

Development of a cloud-based application for the Fracture Liaison Service model of care.

UNLABELLED: The aims of this study are to develop a cloud-based application of the Fracture Liaison Service for practitioners to coordinate the care of osteoporotic patients after suffering primary fractures and provide a performance feedback portal for practitioners to determine quality of care. The application provides continuity of care, improved patient outcomes, and reduced medical costs. INTRODUCTION: The purpose of this study is to describe the content development and functionality of a cloud-based application to broadly deploy the Fracture Liaison Service (FLS) to coordinate post-fracture care for osteoporotic patients. METHODS: The Bone Health Collaborative developed the FLS application in 2013 to support practitioners' access to information and management of patients and provide a feedback portal for practitioners to track their performance in providing quality care. A five-step protocol (identify, inform, initiate, investigate, and iterate) organized osteoporotic post-fracture care-related tasks and timelines for the application. A range of descriptive data about the patient, their medical condition, therapies and care, and current providers can be collected. Seven quality of care measures from the National Quality Forum, The Joint Commission, and the Centers for Medicare and Medicaid Services can be tracked through the application. RESULTS: There are five functional areas including home, tasks, measures, improvement, and data. The home, tasks, and data pages are used to enter patient information and coordinate care using the five-step protocol. Measures and improvement pages are used to enter quality measures and provide practitioners with continuous performance feedback. The application resides within a portal, running on a multitenant, private cloud-based Avedis enterprise registry platform. All data are encrypted in transit and users access the application using a password from any common web browser. CONCLUSION: The application could spread the FLS model of care across the US health care system, provide continuity of care, effectively manage osteoporotic patients, improve outcomes, and reduce medical costs.

Use of Arotinolol Pharmacotherapy to Treat Drug-induced Tremor: A Report of Three Cases.

OBJECTIVE: The aim of the present study is to demonstrate the effect of arotinolol on drug-induced tremor in psychiatric patients. METHODS: This is a case study of three psychiatric patients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of major depressive disorder who were treated in inpatient or outpatient psychiatric settings with antidepressant or antipsychotics. Patients developed tremor. Arotinolol was started to treat the tremor. RESULTS: Drug-induced tremor almost resolved completely. No adverse effects were observed. CONCLUSION: We have presented a case series of drug-induced tremors that responded well to treatment with arotinolol, which appears to be a safe and well-tolerated drug in the dose ranges used. The possible utility of arotinolol to treat drug-induced tremor deserves attention and further investigation.

Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma.

BACKGROUND: Werner protein (WRN) has DNA helicase activity and participates in recombination, replication and repair of DNA. Loss-of-function mutations in WRN gives rise to genetic instability and diseases such as premature ageing and cancer. Upregulation of WRN promotes proliferation and survival of cancer cells. AIM: To evaluate the expression pattern of WRN in closely related skin cancers and their correlation with age, sex and UV exposure. METHODS: Immunohistochemistry was used to investigate expression of WRN in formalin-fixed, paraffin wax-embedded tissue specimens of 9 squamous cell carcinoma (SCC), 15 actinic keratosis (AK), 11 Bowen disease (BD) and 11 normal-appearing peripheral tissue samples, obtained from patients during surgical resections. RESULTS: WRN expression was significantly increased in BD, AK and SCC compared with normal controls, with the mean WRN staining score being highest in BD, followed by AK and SCC. However, age, sex and sun exposure were not associated with WRN expression. CONCLUSIONS: To our knowledge, this is the first report to date investigating the expression of WRN in skin cancers. The overtly high expression of WRN in premalignant lesions and in in situ cancer, with relatively low WRN expression in SCC, may indicate that WRN contributes as a checkpoint for early DNA damage response in skin tumorigenesis.

Decline in extractable antibiotics in manure-based composts during composting.

A wide variety of antibiotics have been detected in natural water samples and this is of potential concern because of the adverse environmental effects of such antibiotic residues. One of the main sources of antibiotics effluence to the surrounding environment is livestock manures which often contain elevated concentrations of veterinary antibiotics (VAs) which survive digestion in the animal stomach following application in animal husbandry practices. In Korea, livestock manures are normally used for compost production indicating that there is potential for antibiotic release to the environment through compost application to agricultural lands. Therefore, reduction of the amount of VAs in composts is crucial. The purpose of this study was to understand the influence of the composting process and the components of the compost on the levels of three common classes of antibiotics (tetracyclines, sulfonamides, and macrolides). Composted materials at different stages of composting were collected from compost manufacturing plants and the variation in antibiotic concentrations was determined. Three different antibiotics, chlortetracycline (CTC), sulfamethazine (SMZ), and tylosin (TYL) at three different concentrations (2, 10, and 20mgkg(-1)) were also applied to a mixture of pig manure and sawdust and the mixtures incubated using a laboratory scale composting apparatus to monitor the changes in antibiotic concentrations during composting together with the physicochemical properties of the composts. During composting, in both field and lab-scale investigations, the concentrations of all three different antibiotics declined below the relevant Korean guideline values (0.8mgkg(-1) for tetracyclines, 0.2mgkg(-1) for sulfonamides and 1.0mgkg(-1) for macrolides). The decline of tetracycline and sulfonamide concentrations was highly dependent on the presence of sawdust while there was no influence of sawdust on TYL decline.

Applicability of the Charm II system for monitoring antibiotic residues in manure-based composts.

The effluence of veterinary antibiotics (VAs) to aquatic and terrestrial environments is of concern due to the potential adverse effects on human health, such as the production of antibiotic resistant bacteria. One of the main pathways for antibiotics to enter the environment is via the application of manure and/or manure-based composts as an alternative organic fertilizer to agricultural lands. While a wide diversity of manure-based composts are produced in Korea, there is currently no regulatory guideline for VA residues. Hence, monitoring and limiting the concentration of VA residues in manure and/or manure-based composts prior to application to the lands is important to mitigate any environmental burden. The current study was conducted to examine the applicability of the Charm II antibiotic test system for monitoring tetracyclines, sulfonamides and macrolides in manure-based composts. The Charm II system was a highly reproducible method for determining whether VA residue concentrations in manure-based compost exceeded specific guideline values. A wide range of manure-based composts and liquid fertilizers commercially available in Korea were examined using the Charm II system to monitor the residues of the target VAs. For this, the guideline concentrations of VA residues (0.8 mg kg(-1) for tetracyclines, 0.2 mg kg(-1) for sulfonamides, and 0.1 mg kg(-1) for macrolides) stated in 'Official Standard of Feeds' under the 'Control of Livestock and Fish Feed Act' in Korea were adopted to establish control points. Of the 70 compost samples examined 12 exceeded 0.8 mg kg(-1) for tetracyclines and 21 exceeded 0.2 mg kg(-1) for sulfonamides. Of the 25 liquid fertilizer samples examined most samples exceeded these prospective guidelines.

Electrochemical detection of pathogen infection using cell chip.

The immobilized cell using self-assembled synthetic oligopeptide was applied to the electrochemical detection of pathogen infection. Thin films based on cysteine-terminated synthetic oligopeptides were fabricated for the immobilization of HeLa cell on gold (Au) substrate. Layer formation and immobilization of the cell were investigated with surface plasmon resonance (SPR) and electrochemical impedance spectroscopy (EIS). Experimental results showed that the thin film of cysteine-terminated synthetic oligopeptide was successfully fabricated and it could be applied for the immobilization of HeLa cells. The adhered living cell was exposed to E. coli O157:H7, which induced the change of SPR angle and electrochemical impedance signal. The proposed cell immobilization method using self-assembly technique can be applied to construct the cell microarray for on-site pathogen monitoring.

Environmental assessment of water, sediment and plants in the Mankyeong River, ROK.

This study was carried out to evaluate water quality, sediment and plant vegetation in eight tributaries of the Mankyeong River for enhancement of natural purification. Among the tributaries, the Iksancheon water had the highest concentration of BOD, T-N and NH4-N due to inflow of swine wastes from the livestock district. The Yucheon water had the highest level of electrical conductivity and SO4(2-) due to inflow of mis-treated wastewater from industrial districts. The Tabcheon had generally similar concentrations of nitrogen and phosphate to that of the upstream of the Mankyeong River: agricultural activity along the Tabcheon appeared to have little negative influence to the water quality. Among various sediments, concentration of organic matter, nitrogen and phosphate were high in the Iksancheon and the Yucheon due to the livestock wastes and industrial wastes. There were 282 species of plants during summer with 43 aquatic plants, 57 hydrophytes, 178 waterside plants and 4 terrestrial plants. Some plant resources were recommended due to much absorption of nitrogen and phosphate for enhancement of natural purification. C. demersum and H. verticillata were recommended in the submerged aquatic plants, H. dubia, N. indica and N. subinteperrimum in the floating leaf aquatic plants, P. communis, Z. latifolia and T. orientalis in the emerged aquatic plants, C. scutata and P. distichum in the waterside plants.

An inhibitor of IkappaB kinase, BMS-345541, blocks endothelial cell adhesion molecule expression and reduces the severity of dextran sulfate sodium-induced colitis in mice.

OBJECTIVE: Inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are characterized by chronic relapsing inflammation. The transcription of many of the proteins which mediate the pathogenesis in inflammatory bowel disease (e.g., TNFalpha, ICAM-1, VCAM-1) is NF-kappaB-dependent. IkappaB kinase is critical in transducing the signal-inducible activation of NF-kappaB and, therefore, represents a potentially promising target for the development of novel agents to treat inflammatory bowel disease and other inflammatory diseases. RESULTS: Here we show that BMS-345541, a highly selective inhibitor of IkappaB kinase, inhibited the TNFalpha-induced expression of both ICAM-1 and VCAM-1 in human umbilical vein endothelial cells at the same concentration range as cytokine expression is inhibited in monocytic cells (IC(50) congruent with 5 microM). Against dextran sulfate sodium-induced colitis in mice, BMS-345541 administered orally at doses of 30 and 100 mg/kg was effective in blocking both clinical and histological endpoints of inflammation and injury. CONCLUSION: This represents the first example of an inhibitor of IkappaB kinase with anti-inflammatory activity in vivo and indicates that inhibitors of IkB kinase show the promise of being highly efficacious in inflammatory disorders such as inflammatory bowel disease.

Innovative peritoneal dialysis: flow-thru and dialysate regeneration.

As the peritoneal dialysis (PD) patient's residual renal function declines, the dialysis dose must be increased. However, the options for increasing the dose are limited to increasing the number of exchanges and/or the volume of each exchange. A review of the literature indicates that the dialysis dose can be significantly increased by flow-through PD, wherein the dialysate flows continuously into the peritoneal cavity through one catheter and out another and/or by regenerating the spent dialysate, thereby, significantly increasing the dialysate flow rate. Flow-thru PD has been used with and without dialysate regeneration. Regeneration has been used with standard inflow/outflow PD. In nearly all cases, substantially increased clearances over standard PD were obtained with reported urea and creatinine clearances as high as 58 and 48 ml/min, respectively. Applying flow-thru to the PD patient would require two catheters or a dual lumen catheter, and to obtain optimum clearances, the dialysate should be pumped through the peritoneal cavity at a high flow rate. Regenerating the dialysate allows high dialysate flow rates while reducing the total amount of dialysate required. For the continuous ambulatory peritoneal dialysis (CAPD) patient, the unit would have to be wearable; whereas for the patient on automated PD, flow-thru and/or regeneration PD could be incorporated into the equipment. With sorbent regeneration, the protein in the spent PD could be purified and returned to the patient thereby minimizing protein loss, increasing ultrafiltration, and enhancing the removal of protein-bound metabolic toxins.

A Proposed Peritoneal-Based Wearable Artificial Kidney.

Ideally, an artificial kidney should simulate the normal kidney in providing continuous metabolic control, removal of toxins, and unrestricted patient freedom. Of the dialysis procedures available, continuous ambulatory peritoneal dialysis (CAPD) comes the closest to this ideal but provides inadequate dialysis and fails to remove protein-bound toxins. A continuous, wearable, peritoneal-based artificial kidney is proposed in which the spent peritoneal dialysate is regenerated using a REDY sorbent cartridge one-tenth the size of the present cartridge, with the urease chemically bound to an inert support to eliminate the possibility of its displacement by protein in the spent dialysate. To simplify the flow path and to increase clearance, the dialysate flow will be through the peritoneal cavity using a dual lumen catheter instead of the traditional in/outflow through a single catheter. At a flow rate of 4 L/hour through the peritoneal cavity, of which 2 L/hour will pass through the sorbent cartridge, it is estimated that the weekly Kt/V will be 6.5 and the creatinine clearance will be 250 L. In addition, any protein in the spent peritoneal dialysate will be stripped of toxins by the sorbents and returned to the patient, thereby minimizing protein loss. The only disposables will be the sorbent cartridge and infusate, which will be changed every 8 hours.

Erythropoietin upregulates angiotensin receptors in cultured rat vascular smooth muscle cells.

OBJECTIVE: Plasma renin is not elevated in recombinant human erythropoietin (rhEPO)-induced hypertension but angiotensin converting enzyme inhibitors reduce blood pressure in both human and animal studies. Since rhEPO elevates renin and angiotensinogen messenger RNAs in angiotensin II target tissues such as the aorta, we explored the actions of rhEPO on renin-angiotensin system-related gene transcription of cultured rat vascular smooth muscle cells. DESIGN AND METHODS: To separate direct actions of rhEPO from those mediated secondarily by potential activation of the renin-angiotensin system, vascular smooth muscle cells were cultured with rhEPO and enalapril to inhibit the angiotensin converting enzyme and losartan to inhibit angiotensin II type 1 receptors. RESULTS: Vascular smooth muscle cells cultured with rhEPO (6-8 units/ml) demonstrated elevations (40-120%) in messenger RNAs of the renin-angiotensin system (renin, angiotensinogen, angiotensin receptor types 1 and 2) and increased levels of several messenger RNAs known to respond to angiotensin II (transforming growth factor-beta, insulin-like growth factor-II, epidermal growth factor, c-fos and platelet-derived growth factor). In contrast, cells cultured in the presence of rhEPO and enalapril or losartan showed elevations of messenger RNA for only the two types of angiotensin II receptor. This increase was higher than that obtained when cells were cultured with rhEPO or either antagonist alone. The increase in specific binding of angiotensin II to cells cultured in the presence of rhEPO and enalapril or rhEPO and losartan paralleled the changes in receptor messenger RNA. CONCLUSIONS: rhEPO exerts its primary action on vascular smooth muscle cells via an increase in angiotensin receptor messenger RNA, resulting in a parallel increase in angiotensin II receptor expression. We suggest that increased receptor expression secondarily mediates the expression of other renin-angiotensin system messenger RNAs, which leads to angiotensin II-responsive gene transcription. The elevation in angiotensin II receptors, as observed in response to rhEPO, may provide a mechanism by which other forms of renin-dependent hypertension are initiated.

Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas.

N-acetyltransferase NAT1, together with enzymes CYP1A2 and NAT2, helps convert heterocyclic amines to mutagens. Epidemiologic studies of the association of variants of these enzymes with colorectal cancer may provide indirect support for a heterocyclic amine mechanism. We used single strand conformation polymorphism and heteroduplex analysis to screen fro mutations in the NAT1 coding region in a case-control study (n = 932) of colorectal adenomas, which are precursors to cancer. Thirteen different single-base mutations were found: C97T, C190T, T402C, G445A-G459A-T640G ( a combination of three mutations), C559T, G560A, A613G, A752T, T777C, G781A, and A787G. Function of novel mutations was tested by bacterial production of enzymes and measurements of Km, Vmax, and stability. However, on 24-control individuals and 18 cases carried an inactivating NAT1 mutation. When combined with our data on the NAT2 acetylation polymorphism, we saw no evidence for an association between N-acetyltransferases and prevalence of adenomas. Larger sample sizes are required for further evaluation.

Prevalence and disease experience rates in Korean physicians.

This study aimed to find out the morbid status of Korean physicians living in Korea, as one part of a feasibility study on the Korean physician cohort. It was performed by mail survey using a self-administered questionnaire from Jan. 1, 1995 through Dec. 31, 1995. Study subjects were 21,552 including 17,877 (81.1%) males and 3,384 (15.5%) females. Person based prevalence rate of disease was 17.7% (18.3% for males and 13.8% for females) with the rate increasing with age. The disease group showing the highest prevalence rate was circulatory diseases (5.16%) for males, and respiratory disease (3.13%) for females. The individual disease showing the highest prevalence rates was hypertension (3.77%) for males and allergic rhinitis (2.25%) for females. The person based disease experience rate was 36.2% (36.9% for males, 32.7% for females) with the rate increasing with age. The disease group showing the highest disease experience rate was digestive disease for both sexes (10.05% for males, 7.42% for females). Individual disease showing the highest disease experience rate was hypertension (5.00%) for males and allergic rhinitis (4.08%) for females. There were different ranks of both prevalence and disease experience rate depending on age in both sexes.