Detecting Variation in Clinical Practice Patterns for Geriatric Trauma Care Using Social Network Analysis.

OBJECTIVE: To characterize hospital-level professional networks of physicians caring for older trauma patients as a function of trauma patient age distribution. BACKGROUND: The causal factors associated with between-hospital variation in geriatric trauma outcomes are poorly understood. Variation in physician practice patterns reflected by differences in professional networks might contribute to hospital-level differences in outcomes for older trauma patients. METHODS: This is a population-based, cross-sectional study of injured older adults (age 65 or above) and their physicians from January 1, 2014, to December 31, 2015, using Health Care Cost and Utilization Project inpatient data and Medicare claims from 158 hospitals in Florida. We used social network analyses to characterize the hospitals in terms of network density, cohesion, small-worldness, and heterogeneity, then used bivariate statistics to assess the relationship between network characteristics and hospital-level proportion of trauma patients who were aged 65 or above. RESULTS: We identified 107,713 older trauma patients and 169,282 patient-physician dyads. The hospital-level proportion of trauma patients who were aged 65 or above ranged from 21.5% to 89.1%. Network density, cohesion, and small-worldness in physician networks were positively correlated with hospital geriatric trauma proportions ( R =0.29, P <0.001; R =0.16, P =0.048; and R =0.19, P <0.001, respectively). Network heterogeneity was negatively correlated with geriatric trauma proportion ( R =0.40, P <0.001). CONCLUSIONS: Characteristics of professional networks among physicians caring for injured older adults are associated with the hospital-level proportion of trauma patients who are older, indicating differences in practice patterns at hospitals with older trauma populations. Associations between interspecialty collaboration and patient outcomes should be explored as an opportunity to improve the treatment of injured older adults.

Transformation of social relationships in COVID-19 America: Remote communication may amplify political echo chambers.

The COVID-19 pandemic, with millions of Americans compelled to stay home and work remotely, presented an opportunity to explore the dynamics of social relationships in a predominantly remote world. Using the 1972-2022 General Social Surveys, we found that the pandemic significantly disrupted the patterns of social gatherings with family, friends, and neighbors but only momentarily. Drawing from the nationwide ego-network surveys of 41,033 Americans from 2020 to 2022, we found that the size and composition of core networks remained stable, although political homophily increased among nonkin relationships compared to previous surveys between 1985 and 2016. Critically, heightened remote communication during the initial phase of the pandemic was associated with increased interaction with the same partisans, although political homophily decreased during the later phase of the pandemic when in-person contacts increased. These results underscore the crucial role of social institutions and social gatherings in promoting spontaneous encounters with diverse political backgrounds.

The Influence of Capping Layers on Tunneling Magnetoresistance and Microstructure in CoFeB/MgO/CoFeB Magnetic Tunnel Junctions upon Annealing.

This study investigates the effects of annealing on the tunnel magnetoresistance (TMR) ratio in CoFeB/MgO/CoFeB-based magnetic tunnel junctions (MTJs) with different capping layers and correlates them with microstructural changes. It is found that the capping layer plays an important role in determining the maximum TMR ratio and the corresponding annealing temperature (Tann). For a Pt capping layer, the TMR reaches ~95% at a Tann of 350 °C, then decreases upon a further increase in Tann. A microstructural analysis reveals that the low TMR is due to severe intermixing in the Pt/CoFeB layers. On the other hand, when introducing a Ta capping layer with suppressed diffusion into the CoFeB layer, the TMR continues to increase with Tann up to 400 °C, reaching ~250%. Our findings indicate that the proper selection of a capping layer can increase the annealing temperature of MTJs so that it becomes compatible with the complementary metal-oxide-semiconductor backend process.

New means, new measures: assessing prescription drug-seeking indicators over 10 years of the opioid epidemic.

BACKGROUND AND AIMS: Prescription drug-seeking (PDS) from multiple prescribers is a primary means of obtaining prescription opioids; however, PDS behavior has probably evolved in response to policy shifts, and there is little agreement about how to operationalize it. We systematically compared the performance of traditional and novel PDS indicators. DESIGN: Longitudinal study using a de-identified commercial claims database. SETTING: United States, 2009-18. PARTICIPANTS: A total of 318 million provider visits from 21.5 million opioid-prescribed patients. MEASUREMENTS: We applied binary classification and generalized linear models to compare predictive accuracy and average marginal effect size predicting future opioid use disorder (OUD), overdose and high morphine milligram equivalents (MME). We compared traditional indicators of PDS to a network centrality measure, PageRank, that reflects the prominence of patients in a co-prescribing network. Analyses used the same data and adjusted for patient demographics, region, SES, diagnoses and health services. FINDINGS: The predictive accuracy of a widely used traditional measure (N + unique doctors and N + unique pharmacies in 90 days) on OUD, overdose and MME decreased between 2009 and 2018, and performed no better than chance (50% accuracy) after 2015. Binarized PageRank measures however exhibited higher predictive accuracy than the traditional binary measures throughout 2009-2018. Continuous indicators of PDS performed better than binary thresholds, with days of Rx performing best overall with 77-93% predictive accuracy. For example, days of Rx had the highest average marginal effects on overdose and OUD: a 1 standard deviation increase in days of Rx was associated with a 6-8% [confidence intervals (CIs) = 0.058-0.061 and 0.078-0.082] increase in the probability of overdose and a 4-5% (CIs = 0.038-0.043 and 0.047-0.053) increase in the probability of OUD. PageRank performed nearly as well or better than traditional indicators of PDS, with predictive performance increasing after 2016. CONCLUSIONS: In the United States, network-based measures appear to have increasing promise for identifying prescription opioid drug-seeking behavior, while indicators based on quantity of providers or pharmacies appear to have decreasing utility.

Substitution of Nonpharmacologic Therapy With Opioid Prescribing for Pain During the COVID-19 Pandemic.

Importance: During the pandemic, access to medical care unrelated to COVID-19 was limited because of concerns about viral spread and corresponding policies. It is critical to assess how these conditions affected modes of pain treatment, given the addiction risks of prescription opioids. Objective: To assess the trends in opioid prescription and nonpharmacologic therapy (ie, physical therapy and complementary medicine) for pain management during the COVID-19 pandemic in 2020 compared with the patterns in 2019. Design, Setting, and Participants: This retrospective, cross-sectional study used weekly claims data from 24 million US patients in a nationwide commercial insurance database (Optum's deidentified Clinformatics Data Mart Database) from January 1, 2019, to September 31, 2020. Among patients with diagnoses of limb, extremity, or joint pain, back pain, and neck pain for each week, patterns of treatment use were identified and evaluated. Data analysis was performed from April 1, 2021, to September 31, 2021. Main Outcomes and Measures: The main outcomes of interest were weekly rates of opioid prescriptions, the strength and duration of related opioid prescriptions, and the use of nonpharmacologic therapy. Transition rates between different treatment options before the outbreak and during the early months of the pandemic were also assessed. Results: A total of 21 430 339 patients (mean [SD] age, 48.6 [24.0] years; 10 960 507 [51.1%] female; 909 061 [4.2%] Asian, 1 688 690 [7.9%] Black, 2 276 075 [10.6%] Hispanic, 11 192 789 [52.2%] White, and 5 363 724 [25.0%] unknown) were enrolled during the first 3 quarters in 2019 and 20 759 788 (mean [SD] age, 47.0 [23.8] years; 10 695 690 [51.5%] female; 798 037 [3.8%] Asian; 1 508 023 [7.3%] Black, 1 976 248 [9.5%] Hispanic, 10 059 597 [48.5%] White, and 6 417 883 [30.9%] unknown) in the first 3 quarters of 2020. During the COVID-19 pandemic, the proportion of patients receiving a pain diagnosis was smaller than that for the same period in 2019 (mean difference, -15.9%; 95% CI, -16.1% to -15.8%). Patients with pain were more likely to receive opioids (mean difference, 3.5%; 95% CI, 3.3%-3.7%) and less likely to receive nonpharmacologic therapy (mean difference, -6.0%; 95% CI, -6.3% to -5.8%), and opioid prescriptions were longer and more potent during the early pandemic in 2020 relative to 2019 (mean difference, 1.07 days; 95% CI, 1.02-1.17 days; mean difference, 0.96 morphine milligram equivalents; 95% CI, 0.76-1.20). Analysis of individuals' transitions between treatment options for pain found that patients were more likely to transition out of nonpharmacologic therapy, replacing it with opioid prescriptions for pain management during the COVID-19 pandemic than in the year before. Conclusions and Relevance: Nonpharmacologic therapy is a benign treatment for pain often recommended instead of opioid therapy. The decrease in nonpharmacologic therapy and increase in opioid prescription during the COVID-19 pandemic found in this cross-sectional study, especially given longer days of prescription and more potent doses, may exacerbate the US opioid epidemic. These findings suggest that it is imperative to investigate the implications of limited medical access on treatment substitution, which may increase patient risk, and implement policies and guidelines to prevent those substitutions.

Systematic Evaluation of State Policy Interventions Targeting the US Opioid Epidemic, 2007-2018.

Importance: In response to the increase in opioid overdose deaths in the United States, many states recently have implemented supply-controlling and harm-reduction policy measures. To date, an updated policy evaluation that considers the full policy landscape has not been conducted. Objective: To evaluate 6 US state-level drug policies to ascertain whether they are associated with a reduction in indicators of prescription opioid abuse, the prevalence of opioid use disorder and overdose, the prescription of medication-assisted treatment (MAT), and drug overdose deaths. Design, Setting, and Participants: This cross-sectional study used drug overdose mortality data from 50 states obtained from the National Vital Statistics System and claims data from 23 million commercially insured patients in the US between 2007 and 2018. Difference-in-differences analysis using panel matching was conducted to evaluate the prevalence of indicators of prescription opioid abuse, opioid use disorder and overdose diagnosis, the prescription of MAT, and drug overdose deaths before and after implementation of 6 state-level policies targeting the opioid epidemic. A random-effects meta-analysis model was used to summarize associations over time for each policy and outcome pair. The data analysis was conducted July 12, 2020. Exposures: State-level drug policy changes to address the increase of opioid-related overdose deaths included prescription drug monitoring program (PDMP) access, mandatory PDMPs, pain clinic laws, prescription limit laws, naloxone access laws, and Good Samaritan laws. Main Outcomes and Measures: The outcomes of interests were quarterly state-level mortality from drug overdoses, known indicators for prescription opioid abuse and doctor shopping, MAT, and prevalence of drug overdose and opioid use disorder. Results: This cross-sectional study of drug overdose mortality data and insurance claims data from 23 million commercially insured patients (12 582 378 female patients [55.1%]; mean [SD] age, 45.9 [19.9] years) in the US between 2007 and 2018 found that mandatory PDMPs were associated with decreases in the proportion of patients taking opioids (-0.729%; 95% CI, -1.011% to -0.447%), with overlapping opioid claims (-0.027%; 95% CI, -0.038% to -0.017%), with daily morphine milligram equivalent greater than 90 (-0.095%; 95% CI, -0.150% to -0.041%), and who engaged in drug seeking (-0.002%; 95% CI, -0.003% to -0.001%). The proportion of patients receiving MAT increased after the enactment of mandatory PDMPs (0.015%; 95% CI, 0.002% to 0.028%), pain clinic laws (0.013%, 95% CI, 0.005%-0.021%), and prescription limit laws (0.034%, 95% CI, 0.020% to 0.049%). Mandatory PDMPs were associated with a decrease in the number of overdose deaths due to natural opioids (-518.5 [95% CI, -728.5 to -308.5] per 300 million people) and methadone (-122.7 [95% CI, -207.5 to -37.8] per 300 million people). Prescription drug monitoring program access policies showed similar results, although these policies were also associated with increases in overdose deaths due to synthetic opioids (380.3 [95% CI, 149.6-610.8] per 300 million people) and cocaine (103.7 [95% CI, 28.0-179.5] per 300 million people). Except for the negative association between prescription limit laws and synthetic opioid deaths (-723.9 [95% CI, -1419.7 to -28.1] per 300 million people), other policies were associated with increasing overdose deaths, especially those attributed to non-prescription opioids such as synthetic opioids and heroin. This includes a positive association between naloxone access laws and the number of deaths attributed to synthetic opioids (1338.2 [95% CI, 662.5 to 2014.0] per 300 million people). Conclusions and Relevance: Although this study found that existing state policies were associated with reduced misuse of prescription opioids, they may have the unintended consequence of motivating those with opioid use disorders to access the illicit drug market, potentially increasing overdose mortality. This finding suggests that there is no easy policy solution to reverse the epidemic of opioid dependence and mortality in the US.

A measure of centrality in cyclic diffusion processes: Walk-betweenness.

Unlike many traditional measures of centrality based on paths that do not allow any repeated nodes or lines, we propose a new measure of centrality based on walks, walk-betweenness, that allows any number of repeated nodes or lines. To illustrate the value of walk-betweenness, we examine the transmission of syphilis in Chicago area and the diffusion of microfinance in 43 rural Indian villages. Walk-betweenness allows us to identify hidden bridging communities in Chicago that were essential in the transmission dynamics. We also find that village leaders with high walk-betweenness are more likely to accelerate the rate of microfinance take-up among their followers, outperforming other traditional centrality measures in regression analyses.

Cross-level sociodemographic homogeneity alters individual risk for completed suicide.

Among deaths of despair, the individual and community correlates of US suicides have been consistently identified and are well known. However, the suicide rate has been stubbornly unyielding to reduction efforts, promoting calls for novel research directions. Linking levels of influence has been proposed in theory but blocked by data limitations in the United States. Guided by theories on the importance of connectedness and responding to unique data challenges of low base rates, geographical dispersion, and appropriate comparison groups, we attempt a harmonization of the National Violent Death Reporting System (NVDRS) and the American Community Survey (ACS) to match individual and county-level risks. We theorize cross-level sociodemographic homogeneity between individuals and communities, which we refer to as "social similarity" or "sameness," focusing on whether having like-others in the community moderates individual suicide risks. While analyses from this new Multilevel Suicide Data for the United States (MSD-US) replicate several individual and contextual findings, considering sameness changes usual understandings of risk in two critical ways. First, high individual risk for suicide among those who are younger, not US born, widowed or married, unemployed, or have physical disabilities is cut substantially with greater sameness. Second, this moderating pattern flips for Native Americans, Alaska Natives, Asians, and Hispanics, as well as among native-born and unmarried individuals, where low individual suicide risk increases significantly with greater social similarity. Results mark the joint influence of social structure and culture, deliver unique insights on the complexity of connectedness in suicide, and offer considerations for policy and practice.

On-screen fingerprint sensor with optically and electrically tailored transparent electrode patterns for use on high-resolution mobile displays.

In this study, a mutual capacitive-type on-screen fingerprint sensor, which can recognize fingerprints on a display screen to provide smartphones with full-screen displays with a minimal bezel area, is fabricated. On-screen fingerprint sensors are fabricated using an indium tin oxide transparent conductor with a sheet resistance of ~10 Ω/sq. and a transmittance of ~94% (~86% with the substrate effect) in the visible wavelength range, and assembled onto a display panel. Even at this high transmittance, the electrodes can degrade the display quality when they are placed on the display. The interference between periodic display pixel arrays and sensor patterns can lead to the Moiré phenomenon. It is necessary to find an appropriate sensor pattern that minimizes the Moiré pattern, while maintaining the signal sensitivity. To search for appropriate patterns, a numerical calculation is carried out over wide ranges of pitches and rotation angles. The range is narrowed for an experimental evaluation, which is used to finally determine the sensor design. As the selected sensor pitches are too small to detect capacitance variations, three unit patterns are electrically connected to obtain a unit block generating a larger signal. By applying the selected sensor pattern and circuit driving by block, fingerprint sensing on a display is demonstrated with a prototype built on a commercial smartphone.

Moiré-free fingerprint sensors based on multilayer oxide-metal-oxide electrodes.

The display quality of touchscreen devices with on-screen fingerprint sensors is reduced by moiré patterns, interference phenomena caused by an overlap between the pixel pattern of the display, and the electrode pattern of the fingerprint sensor. A promising strategy for resolving this issue is to reduce the visibility of the moiré pattern, by including a filling layer with a transmittance similar to that of the electrodes, between the different patterns. We propose a moiré-free fingerprint sensor that uses an oxide-metal-oxide (IZO/Ag/IZO) multilayer as a highly transparent electrode. To verify the moiré reduction effect, we conducted a two-dimensional spectral analysis to calculate the spatial frequencies of the superimposed image of the display and the sensor patterns, and demonstrated experimentally that the proposed electrode greatly reduces the undesirable moiré phenomenon.

Work environments and exposure to hazardous substances in korean tire manufacturing.

OBJECTIVES: The purpose of this study is to evaluate the tire manufacturing work environments extensively and to identify workers' exposure to hazardous substances in various work processes. METHODS: Personal air sampling was conducted to measure polycyclic aromatic hydrocarbons, carbon disulfide, 1,3-butadiene, styrene, methyl isobutyl ketone, methylcyclohexane, formaldehyde, sulfur dioxide, and rubber fume in tire manufacturing plants using the National Institute for Occupational Safety Health Manual of Analytical Methods. Noise, carbon monoxide, and heat stress exposure were evaluated using direct reading instruments. Past concentrations of rubber fume were assessed using regression analysis of total particulate data from 2003 to 2007, after identifying the correlation between the concentration of total particulate and rubber fume. RESULTS: Workers were exposed to rubber fume that exceeded 0.6 mg/m(3), the maximum exposure limit of the UK, in curing and production management processes. Forty-seven percent of workers were exposed to noise levels exceeding 85 dBA. Workers in the production management process were exposed to 28.1℃ (wet bulb globe temperature value, WBGT value) even when the outdoor atmosphere was 2.7℃ (WBGT value). Exposures to other substances were below the limit of detection or under a tenth of the threshold limit values given by the American Conference of Governmental Industrial Hygienists. CONCLUSION: To better classify exposure groups and to improve work environments, examining closely at rubber fume components and temperature as risk indicators in tire manufacturing is recommended.

Social network effects on post-traumatic stress disorder (PTSD) in female North Korean immigrants.

OBJECTIVES: The goal of this paper is to examine the social network effects on post-traumatic sdress disorder (PTSD) in female North Korean immigrants who entered South Korea in 2007. Specifically, it attempts to verify if the density and composition of networks make a difference after controlling for the network size. METHODS: A multivariate logistic regression is used to probe the effects of social networks using the North Korean Immigrant Panel data set. Because the data set had only completed its initial survey when this paper was written, the analysis was cross-sectional. RESULTS: The size of the support networks was systematically related to PTSD. Female North Korean immigrants with more supporting ties were less likely to develop PTSD, even after controlling for other risk factors (odds-ratio for one more tie was 0.8). However, once we control for the size of the network, neither the density nor the composition of the networks remains statistically significant. CONCLUSIONS: The prevalence of the PTSD among female North Korean immigrants is alarmingly high, and regardless of the characteristics of supporting network members, the size of the supporting networks provides substantial protection. This implies that a simple strategy that focuses on increasing the number of supporting ties will be effective among North Korean immigrants who entered South Korea in recent years.

Fabrication and MFM study of 60 nm track-pitch discrete track media.

Discrete track magnetic recording media with a 60 nm track pitch and prewritten servo patterns were fabricated and tested for read/write performance, and a feasibility analysis of the embedded servo was performed. The fabrication process consisted of ultraviolet nanoimprint lithography (UV-NIL) and sequential ion beam etching on a conventional perpendicular magnetic recording medium. Magnetic patterns were written to the fabricated tracks at 700 kilo flux changes per inch (kFCI) using a spin stand and were read using magnetic force microscopy (MFM), with a resulting signal-to-noise ratio (SNR) of 12.15 dB. The servo pattern was also visualized with MFM. These results demonstrated the feasibility of writing to a 30 nm wide discrete data track and the workability of the embedded servo pattern.

Characteristics of Occupational Exposure to Benzene during Turnaround in the Petrochemical Industries.

OBJECTIVES: The level of benzene exposure in the petrochemical industry during regular operation has been well established, but not in turnaround (TA), where high exposure may occur. In this study, the characteristics of occupational exposure to benzene during TA in the petrochemical companies were investigated in order to determine the best management strategies and improve the working environment. This was accomplished by evaluating the exposure level for the workers working in environments where benzene was being produced or used as an ingredient during the unit process. METHODS: From 2003 to 2008, a total of 705 workers in three petrochemical companies in Korea were studied. Long- and short-term (< 1 hr) samples were taken during TAs. TA was classified into three stages: shut-down, maintenance and start-up. All works were classified into 12 occupation categories. RESULTS: The long-term geometric mean (GM) benzene exposure level was 0.025 (5.82) ppm (0.005-42.120 ppm) and the short-term exposure concentration during TA was 0.020 (17.42) ppm (0.005-61.855 ppm). The proportions of TA samples exceeding the time-weighted average, occupational exposure level (TWA-OEL in Korea, 1 ppm) and the short-term exposure limit (STEL-OEL, 5 ppm) were 4.1% (20 samples of 488) and 6.0% (13 samples of 217), respectively. The results for the benzene exposure levels and the rates of exceeding the OEL were both statistically significant (p < 0.05). Among the 12 job categories of petrochemical workers, mechanical engineers, plumbers, welders, fieldman and scaffolding workers exhibited long-term samples that exceeded the OEL of benzene, and the rate of exceeding the OEL was statistically significant for the first two occupations (p < 0.05). CONCLUSION: These findings suggest that the periodic work environment must be assessed during non-routine works such as TA.

Involvement of Ca2+/calmodulin kinase II (CaMK II) in genistein-induced potentiation of leucine/glutamine-stimulated insulin secretion.

Genistein has been reported to potentiate glucose-stimulated insulin secretion (GSIS). Inhibitory activity on tyrosine kinase or activation of protein kinase A (PKA) was shown to play a role in the genistein-induced potentiation effect on GSIS. The aim of the present study was to elucidate the mechanism of genistein-induced potentiation of insulin secretion. Genistein augmented insulin secretion in INS-1 cells stimulated by various energy-generating nutrients such as glucose, pyruvate, or leucine/glutamine (Leu/Gln), but not the secretion stimulated by depolarizing agents such as KCl and tolbutamide, or Ca(2+) channel opener Bay K8644. Genistein at a concentration of 50 µM showed a maximum potentiation effect on Leu/Gln-stimulated insulin secretion, but this was not sufficient to inhibit the activity of tyrosine kinase. Inhibitor studies as well as immunoblotting analysis demonstrated that activation of PKA was little involved in genistein-induced potentiation of Leu/Gln-stimulated insulin secretion. On the other hand, all the inhibitors of Ca(2+)/calmodulin kinase II tested, significantly diminished genistein-induced potentiation. Genistein also elevated the levels of [Ca(2+)]i and phospho-CaMK II. Furthermore, genistein augmented Leu/Gln-stimulated insulin secretion in CaMK II-overexpressing INS-1 cells. These data suggest that the activation of CaMK II played a role in genistein-induced potentiation of insulin secretion.

Comparison of chemical compositions and antimicrobial activities of essential oils from three conifer trees; Pinus densiflora, Cryptomeria japonica, and Chamaecyparis obtusa.

The chemical compositions, and antibacterial and antifungal effects of essential oils extracted from three coniferous species, Pinus densiflora, Cryptomeria japonica, and Chamaecyparis obtusa, were investigated. Gas chromatography mass analysis of the essential oils revealed that the major components and the percentage of each essential oil were 16.66% beta-phellandrene and 14.85% alpha-pinene in P. densiflora; 31.45% kaur-16-ene and 11.06% sabinene in C. japonica; and 18.75% bicyclo [2, 2, 1] heptan-2-ol and 17.41% 2-carene in Ch. obtusa. The antimicrobial assay by agar disc diffusion method showed that 2.2 microg of Ch. obtusa oil inhibited most effectively the growth of Escherichia coli ATCC 33312 and Klebsiella oxytoca ATCC 10031, whereas the C. japonica oil gave weak antimicrobial activity. The minimal inhibitory concentration (MIC) values for bacterial strains were in the range of 5.45-21.8 mg/ml depending on essential oils, but most Gram-negative bacteria were resistant even at 21.8 mg oil/ml. P. densiflora oil showed the most effective antifungal activity and the MIC values for Cryptococcus neoformans B42419 and Candida glabrata YFCC 062CCM 11658 were as low as 0.545 and 2.18 mg/ml, respectively. Cryp. neoformans B42419 was the most sensitive to all essential oils in the range of 0.545-2.18 mg/ml. Our data clearly showed that the essential oils from the three conifers had effective antimicrobial activity, especially against fungi.

The fabrication of Co-Pt electro-deposited bit patterned media with nanoimprint lithography.

Bit patterned media with 25 nm hole diameter and 50 nm pitch size were fabricated with serial processes comprising master patterning with electron-beam lithography, a Si etching process, multi-layer soft stamp replication, and UV nanoimprinting, followed by Co-Pt magnetic material filling by electro-deposition. From these processes, the designed patterns were well defined, and perpendicular magnetic anisotropy of the fabricated bit patterned media was obtained.

Role of the RAM network in cell polarity and hyphal morphogenesis in Candida albicans.

RAM (regulation of Ace2p transcription factor and polarized morphogenesis) is a conserved signaling network that regulates polarized morphogenesis in yeast, worms, flies, and humans. To investigate the role of the RAM network in cell polarity and hyphal morphogenesis of Candida albicans, each of the C. albicans RAM genes (CaCBK1, CaMOB2, CaKIC1, CaPAG1, CaHYM1, and CaSOG2) was deleted. All C. albicans RAM mutants exhibited hypersensitivity to cell-wall- or membrane-perturbing agents, exhibiting cell-separation defects, a multinucleate phenotype and loss of cell polarity. Yeast two-hybrid and in vivo functional analyses of CaCbk1p and its activator, CaMob2p, the key factors in the RAM network, demonstrated that the direct interaction between the SMA domain of CaCbk1p and the Mob1/phocein domain of CaMob2p was necessary for hyphal growth of C. albicans. Genome-wide transcription profiling of a Camob2 mutant suggested that the RAM network played a role in serum- and antifungal azoles-induced activation of ergosterol biosynthesis genes, especially those involved in the late steps of ergosterol biosynthesis, and might be associated, at least indirectly, with the Tup1p-Nrg1p pathway. Collectively, these results demonstrate that the RAM network is critically required for hyphal growth as well as normal vegetative growth in C. albicans.

Comparative analyses of complex formation and binding sites between human tumor necrosis factor-alpha and its three antagonists elucidate their different neutralizing mechanisms.

Tumor necrosis factor-alpha (TNFalpha)-blocking therapy, using biologic TNFalpha antagonists, has been approved for the treatment of several diseases including rheumatoid arthritis, psoriasis and Crohn's disease. There have been few detailed studies of binding characterizations for the complex formation by TNFalpha and clinically relevant antagonists, particularly Infliximab (Remicade) and Etanercept (Enbrel). Here we characterized the binding stoichiometry and size of soluble TNFalpha-antagonist complexes and identified energetically important binding sites on TNFalpha for the three antagonists, Etanercept, Infliximab, and the recently developed humanized TNFalpha neutralizing monoclonal antibody, YHB1411-2. Size-exclusion chromatography and dynamic light scattering analyses revealed that the three antagonists formed distinct thermodynamically stable TNFalpha-antagonist complexes that exhibited differences in their size and composition. Energetically important binding residues on TNFalpha were identified for each antagonist by a sequence of experiments that consisted of competition binding assays, fragmentations, loop mutations, and single-point mutations using yeast surface-displayed TNFalpha, which was further confirmed for solubly purified TNFalpha mutants by surface plasmon resonance technique. Analyses of the binding geometry based on binding site location, spatial constraints, and valency satisfaction allowed us to interpret the thermodynamically stable complexes as follows: one molecule of Etanercept and one molecule of trimeric TNFalpha (Etanercept1-TNFalpha1), Infliximab6-TNFalpha3, and YHB1411-2(4)-TNFalpha2. The distinct features of the soluble antagonist-TNFalpha complex formation among the antagonists may give further insights into their different neutralizing mechanisms and pharmacokinetic profiles.