cssi/SciSciGPT-SciSciNet huggingface dataset:
RNA polymerase unwinds an 11-base pair segment of a phage T7 promoter.

WHEN RNA polymerase binds to a promoter site, it must unwind part of the DNA double helix so as to expose the template bases. Wang et al.1, Melnikova et al.2 and Hsieh and Wang3 have used different experimental techniques to measure the degree of unwinding. Their estimates range from 7 (ref. 1) to 15 (ref. 2) base pairs unwound per bound Escherichia coli RNA polymerase (EC 2.7.7.6). These studies, however, do not establish which part of a promoter is melted out. A new technique described here directly proves unwinding and furthermore identifies the exact region that RNA polymerase opens in the A3 promoter of phage T7. This promoter is one of three strong E. coli RNA polymerase promoters used early in the life cycle of phage T7 (ref. 4).
The relative importance of random error and observation frequency in detecting trends in upper tropospheric water vapor

Recent published work assessed the amount of time to detect trends in atmospheric water vapor over the coming century. We address the same question and conclude that under the most optimistic scenarios and assuming perfect data (i.e., observations with no measurement uncertainty) the time to detect trends will be at least 12 years at approximately 200 hPa in the upper troposphere. Our times to detect trends are therefore shorter than those recently reported and this difference is affected by data sources used, method of processing the data, geographic location and pressure level in the atmosphere where the analyses were performed. We then consider the question of how instrumental uncertainty plays into the assessment of time to detect trends. We conclude that due to the high natural variability in atmospheric water vapor, the amount of time to detect trends in the upper troposphere is relatively insensitive to instrumental random uncertainty and that it is much more important to increase the frequency of measurement than to decrease the random error in the measurement. This is put in the context of international networks such as the Global Climate Observing System (GCOS) Reference Upper-Air Network (GRUAN) and the Network for the Detection of Atmospheric Composition Change (NDACC) that are tasked with developing time series of climate quality water vapor data.
Fusion of insulin receptor ectodomains to immunoglobulin constant domains reproduces high-affinity insulin binding in vitro

A unique feature of the insulin receptor is that it is dimeric in the absence of ligand. Dimerization of two adjacent transmembrane domain (TMD) alpha helices has been shown to be critical in receptor kinase activation. Moreover, previous work has suggested that the TMD is involved in stabilizing the high-affinity binding site; soluble receptors expressed after simple truncation at the ectodomain-TMD junction have reduced affinity for insulin. To further examine this issue, we have replaced the TMD and intracellular domain of the soluble human insulin receptor (HIRs) with constant domains from immunoglobulin Fc and lambda subunits (HIRs-Fc and HIRs-lambda). Studies of receptor biosynthesis and binding characteristics were performed following transient transfection of receptor cDNAs into human embryonal kidney 293 cells. Each hybrid receptor was initially synthesized as a single chain proreceptor, followed by cleavage into alpha- and beta-Fc or beta-lambda subunits. The majority of secreted protein appeared in the cell medium as fully processed heterotetramer. Fc fragments released from HIRs-Fc by papain digestion and analyzed by nonreducing SDS-polyacrylamide gel electrophoresis were dimeric. Furthermore, dissociation constants for both chimeras were similar to those for the full-length holoreceptor (wild-type receptor, Kd1 = 200 pM and Kd2 = 2 nM; HIRs-Fc, Kd1 = 200 pM and Kd2 = 40 nM; and HIRs-lambda, Kd1 = 200 pM and Kd2 = 5 nM). These results extend previous observations that dimerization of the membrane-proximal ectodomain is necessary to maintain an intact high-affinity insulin-binding site.
Addressing Rising Health Care Costs — A View from the Congressional Budget Office

Peter Orszag and Philip Ellis write that a variety of evidence suggests that there are opportunities to constrain health care costs without incurring adverse health consequences. Dr. Peter Orszag discusses the rising cost of health care and the potential for slowing the growth by undertaking and applying comparative efficacy studies. Dr. Orszag is the director of the Congressional Budget Office.
Stability analysis of entrainment by two periodic inputs with a fixed delay

Abstract We were able to predict stable entrainments for an open-loop neural circuit in which an endogenously rhythmic neuron is driven by two periodic inputs separated by a fixed delay, using linear stability analysis about an assumed entrainment as well as a local linearization of the measured phase resetting curve. An example using Morris Lecar oscillators found multistable entrainments for a fixed delay. A fixed delay could be applicable to interneurons that exhibit post-inhibitory rebound bursting. This research is part of an effort to extend the applicability of our previously developed methods to analyze circuits that underlie central pattern generation.
Current Status of Child and Adolescent Medical-Psychiatric Units

The rationale for child and adolescent medical psychiatric units (CAMPUs) is given, primarily emphasizing differences from adult medical-psychiatry units. Results from a national survey describe the current status of CAMPUs in the continental United States. A total of 32 units were identified, with an additional 7 hospitals planning to establish a CAMPU. Levels of treatment intensity of CAMPUs were clarified, the general administrative structure of the 11 most treatment-intensive CAMPUs were described, and their combined patient populations are descriptively analyzed to present empirical data on the numbers and types of patients currently treated on such units.
Anode Interfacial Engineering Approaches to Enhancing Anode/Hole Transport Layer Interfacial Stability and Charge Injection Efficiency in Organic Light-Emitting Diodes

The integrity of anode/organic interfacial contact is shown to be crucial to the performance and stability of archetypical small molecule organic light-emitting diodes (OLEDs). In this contribution, vapor-deposited lipophilic, hole-transporting 1,4-bis(phenyl-m-tolylamino)biphenyl (TPD) and 1,4-bis(1-naphthylphenylamino)biphenyl (NPB) thin films are shown to undergo decohesion on ITO anode surfaces under mild heating. An effective approach to ameliorate such interfacial decohesion is introduction, via self-assembly or spin-coating, of covalently bound N(p-C6H4CH2CH2CH2SiCl3)3 (TAA)- and 4,4‘-bis[(p-trichlorosilylpropylphenyl)phenylamino]biphenyl (TPD-Si2)-derived adhesion/injection layers at the anode/hole transport layer interface. The resulting angstrom-scale hole transport layers prevent decohesion of vapor-deposited hole transport layers and significantly enhance OLED hole injection fluence. OLEDs fabricated with these modified interfaces exhibit appreciably reduced turn-on voltages, considerably high...
Autonomic and baroreflex function after captopril in hypertension

Abstract Absent reflex tachycardia with captopril therapy suggests blunting of circulatory reflexes, perhaps contributing to antihypertensive efficacy, and angiotensin converting enzyme inhibition may alter sympathetic function. Captopril effects on autonomic function were investigated in five severe hypertensive patients. Mean blood pressure fell in all patients (from 141 ± 6 to 119 ± 7 mm Hg, p p > 0.1) on captopril. Captopril did not alter baroreflex sensitivity as tested by amyl nitrite hypotension or phenylephrine hypertension (both p > 0.1). Comparison of these severely hypertensive patients to age matched normotensive control subjects did reveal markedly blunted baroreflex sensitivity in both the amyl nitrite test (by 89%, p p p p
Estrone and estradiol-17β concentration in tissue of the scleractinian coral, Montipora verrucosa

Spawnings of scleractinian corals are affected by light, temperature, and other environmental cues, but no studies elucidate physiological mechanisms that regulate coral gametogenesis. We hypothesized that estrogens may act as bioregulators of coral reproduction. Estrone (E1) and estradiol-17 beta (E2) concentrations were measured in homogenates of tissue and skeleton from M. verrucosa. Tissue samples were collected monthly throughout the year, and more frequently in July and August around spawning. Steroids were extracted with diethyl ether, purified via celite chromatography and assayed with radioimmunoassay. Non-specific binding in coral tissue varied with sample weight and was elevated relative to standards. Monthly mean E1 ranged from 20-70 ng E1 g ash-free dry weight (AFDW)-1, with highest values in April. Smaller asynchronous peaks occurred in early July, prior to spawning. Monthly mean E2 ranged from 8-25 ng E2 g AFDW-1, with highest values in February and March. Peaks in E2 preceded peaks in E1, indicating metabolism of a pool of estrogen. E1 was positively correlated with protein concentration, which is consistent with a bioregulatory role of estrogens. Estrogen peaks in spring and prior to the July spawn corroborate our hypothesis that estrogens regulate coral gametogenesis and spawning.
Adenosine transport by a variant of C1300 murine neuroblastoma cells deficient in adenosine kinase.

The uptake of adenosine by an adenosine kinase deficient variant of C1300 murine neuroblastoma cells has been studied in the absence and in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, a potent adenine deaminase inhibitor. Although 100 μM inhibitor completely blocks the metabolism of adenosine under the conditions studied, the uptake of adenosine is concentrative, i.e., the intracellular adenosine concentration exceeds the extracellular concentration. This concentrative effect decreases as the concentration of adenosine increases and is hypothesized to be due to the binding of adenosine to an intracellular component. Despite this concentrative effect, we believe that the kinetics of uptake, as determined in experiments with short (10–20 s) uptake periods, reflect the kinetics of adenosine transport by a facilitated diffusion process. This nucleoside transport system appears to be nonspecific in that the transport of adenosine is competitively antagonized by thymidine. It does not appear to be necessary to inhibit adenosine deaminase in order to study transport in these cells as the Km for transport is not affected by the presence of erythro-9-(2-hydroxy-3-nonyl)adenine. However, erythro-9-(2-hydroxy-3-nonyl)adenine does depress the V for transport. This effect of the inhibitor is probably not due to the inhibition of adenosine deaminase as the transport of thymidine is similarly affected.
Reduction of plantar heel pressures: Insole design using finite element analysis

Plantar heel pain is a common condition that is often exacerbated by the repetitive stresses of walking. Treatment usually includes an in-shoe intervention designed to reduce plantar pressure under the heel by using insoles and a variety of off-the-shelf products. The design process for these products is often intuitive in nature and does not always rely on scientifically derived guidelines. Finite element analysis provides an efficient computational framework to investigate the performance of a large number of designs for optimal plantar pressure reduction. In this study, we used two-dimensional plane strain finite element modeling to investigate 27 insole designs. Combinations of three insole conformity levels (flat, half conforming, full conforming), three insole thickness values (6.3, 9.5 and 12.7 mm) and three insole materials (Poron Cushioning, Microcel Puff Lite and Microcel Puff) were simulated during the early support phase of gait. Plantar pressures predicted by the model were validated by experimental trials conducted in the same subject whose heel was modeled by loading the bare foot on a rigid surface and on foam mats. Conformity of the insole was the most important design variable, whereas peak pressures were relatively insensitive to insole material selection. The model predicted a 24% relief in pressure compared to barefoot conditions when using flat insoles; the reduction increased up to 44% for full conforming insoles.
Individual- and population-level toxicity of the insecticide, spirotetramat and the agricultural adjuvant, Destiny to the Cladoceran, Ceriodaphnia dubia.

The effects of the tetramic acid insecticide, spirotetramat and the agricultural adjuvant, Destiny, were evaluated on the Cladoceran, Ceriodaphnia dubia. These compounds were evaluated separately and as a mixture because they can be applied together for control of certain crop pests and therefore have the potential to enter surface water as a binary mixture. Acute mortality estimates (48 h) were developed followed by chronic exposure (8 days) studies where several population parameters were recorded. Acute LC50 and 95% CL for spirotetramat and Destiny were estimated to be 23.8 (14.5–35.4) and 26.71 (20.8–34.0) mg/l, respectively. Thus, spirotetramat and Destiny were equitoxic to C. dubia at LC50. For the chronic population study, C. dubia populations were exposed to a range of concentrations for spirotetramat and Destiny singly and as a mixture. Each chemical alone reduced the number of founding individuals, offspring/female, final population size, and population growth rate in a concentration-dependent manner. However, exposure to the mixture caused significantly greater reductions in these parameters than either compound alone. These results indicate that agricultural adjuvants and pesticides may cause more damage to aquatic organisms as a mixture than either product alone. Therefore, future evaluations of pesticide effects should consider the effects of adjuvants as a mixture with pesticides when these products are recommended to be applied together for pest control.
The paradox of pharmacy: A profession's house divided

Objective To describe the paradox in pharmacy between the vision of patient care and the reality of community pharmacy practice and to explore how integrated reimbursement for the retail prescription and linking cognitive patient care services directly to prescription processing could benefit the profession. Summary A dichotomy exists between what many pharmacists do and what they’ve been trained to do. Pharmacy leaders have formulated a vision for pharmacists to become more involved in direct patient care. All graduates now receive PharmD-level training, and some leaders call for requirements of postgraduate residency training and board certification for pharmacists who provide patient care. How such requirements would relate to community pharmacy practice is unclear. The retail prescription remains the primary link between the pharmacist and the health care consumer. Cognitive services, such as medication therapy management (MTM), need to be integrated into the standard workflow of community pharmacies so as to become a natural extension of the professional services rendered in the process of filling a prescription. Current prescription fees are not sufficient to support legitimate professional services. A proposed integrated pricing system for retail prescriptions includes a $15 professional fee that is scaled upward for value-added services, such as MTM. Conclusion Pharmacy includes a diversity of practice that has historically been a source of division. For pharmacists to reach their potential as patient care providers, the various factions within the profession must forge a unified vision of the future that addresses all realms of practice.
The impact of vascular leg disorders on physical activity in methadone-maintained adults.

Chronic venous disorders (CVD) and peripheral arterial disease (PAD) may affect diverse physical activity domains. How CVD and PAD and other relevant variables affect physical activity was examined in 569 opioid-addicted adults. Both CVD and PAD were significantly inversely related to daily walking, sports, and active living. Effects remained significant in the latent variable regression after controlling covariates. Overall activity was very low; most participants walked less than a half mile daily and rarely engaged in sports. Motivation for physical activity was the strongest predictor (β = .55) of daily physical activity. Health-care professionals promoting physical activity for injection users should consider the vascular health of their legs and motivational variables in addition to general health. © 2010 Wiley Periodicals, Inc. Res Nurs Health 33:426–440, 2010
Metabolism of Thyroid Hormones by Rat Thyroid Tissue in Vitro

Rat thyroid lobes or hemilobes have been incubated in Krebs-Ringer phosphate buffer containing labeled T4 and/or T3, and the products were separated by paper chromatography. Labeled T4 was actively degraded; about half of the T4 metabolized was recovered as T3. Labeled T3 was also metabolized, but less rapidly than T4. Other than T3 produced from T4, the major products from both hormones were inorganic iodide and iodoprotein; the latter was presumably a secondary product of iodide organification because its formation was inhibited by hypoxia and methimazole. Feeding the animals a low iodine diet increased their hormone-metabolizing activity. Incubation under nitrogen did not affect the rate of T4 degradation, but partially inhibited T3 degradation. Degradation of both hormones was unchanged in the presence of methimazole and ascorbate, was markedly inhibited by 1 mM propylthiouracil (PTU), and was partially inhibited by azide and cyanide. Thyroid tissues concentrated both hormones, tissue to medium gradie...
A FETI‐based domain decomposition technique for time‐dependent first‐order systems based on a DAE approach

We present a novel partitioned coupling algorithm to solve first-order time-dependent non-linear problems (e.g. transient heat conduction). The spatial domain is partitioned into a set of totally disconnected subdomains. The continuity conditions at the interface are modeled using a dual Schur formulation where the Lagrange multipliers represent the interface fluxes (or the reaction forces) that are required to maintain the continuity conditions. The interface equations along with the subdomain equations lead to a system of differential algebraic equations (DAEs). For the resulting equations a numerical algorithm is developed, which includes choosing appropriate constraint stabilization techniques. The algorithm first solves for the interface Lagrange multipliers, which are subsequently used to advance the solution in the subdomains. The proposed coupling algorithm enables arbitrary numeric schemes to be coupled with different time steps (i.e. it allows subcycling) in each subdomain. This implies that existing software and numerical techniques can be used to solve each subdomain separately. The coupling algorithm can also be applied to multiple subdomains and is suitable for parallel computers. We present examples showing the feasibility of the proposed coupling algorithm. Copyright © 2008 John Wiley & Sons, Ltd.
Optimal estimates for the inhomogeneous problem for the bi-Laplacian in three-dimensional Lipschitz domains

We establish the well-posedness of the inhomogeneous Dirichlet problem for Δ2 in arbitrary Lipschitz domains in $ {\mathbb{R}^3} $ , with data from Besov–Triebel–Lizorkin spaces, for the optimal range of indices. The main novel contribution is to allow for certain nonlocally convex spaces to be considered, and to establish integral representations for the solution. Bibliography: 57 titles. Illustrations: 1 figure.
Physical control of biological processes in the central equatorial Pacific Ocean

Abstract A five-component (phytoplankton, zooplankton, ammonium, nitrate, detritus) physical–biological model was developed to investigate the effects of physical processes on daily to interannual time scales, on the lower trophic levels of the central equatorial Pacific. Many of the biological processes included in the ecosystem model respond to environmental fluctuations with time scales between 1 and 10 d, which are not typically resolved by basin- to global-scale circulation models. Therefore, the equatorial Pacific ecosystem model is forced using daily information (solar radiation, velocity, temperature) from the Tropical Atmosphere Ocean (TAO) mooring array. The ecosystem model also requires vertical velocity information which necessitated the development of a method for computing daily vertical velocities from the TAO array. Much of the variability in primary production, plankton and nutrient concentrations observed in 1992 during the US Joint Global Ocean Flux Study Equatorial Pacific Process Study time-series cruises (TS1 and TS2), is well reproduced in the model simulations. Simulations demonstrate that lower primary productivities during TS1 as compared to TS2 result from the deeper thermocline that persisted during TS1 as a result of El Nino conditions; however, because of the simultaneous reduction in grazing pressure, simulated chlorophyll levels are similar for these two time periods. Simulations of this single-species ecosystem model successfully reproduce data collected both during and after the El Nino, suggesting that species composition changes are not of first-order importance when examining the effects of the 1991–92 El Nino on the equatorial Pacific ecosystem. A 60–70% increase in chlorophyll concentration and a 400% increase in the chlorophyll contribution by diatoms was associated with the passage of a tropical instability wave (20-d period) across the study site during TS2. This period of high chlorophyll concentration and diatom abundance coincided temporally with strong northward velocities and strong downwelling velocities in the upper euphotic zone. Observations and simulations suggest that this increase in chlorophyll concentration and change in species composition not only results from in situ diatom growth stimulated by increased iron concentrations, but also results from the advection of diatoms toward the convergent front located along the leading (western) edge of the instability wave. Equatorially trapped internal gravity waves can also stimulate in situ phytoplankton growth as high-frequency vertical motions introduce limiting micronutrients, such as iron, into the euphotic zone. Because iron can be taken up by the picoplankton on time scales much shorter than the wave period (6–8 days), these waves may provide a mechanism for effecting a large flux of iron into the euphotic zone. Exclusion of these high-frequency motions results in an iron flux to the euphotic zone that may be underestimated by more than 30%.
When the Gut Talks to Bone

Mutations in LRP5, a coreceptor for Wnt proteins, cause the disease osteoporosis pseudoglioma. A new study by Yadav et al. (2008) now challenges the view that LRP5 controls bone mass through Wnt signaling in bone and argues instead that LRP5 regulates bone mass indirectly through its effects on serotonin synthesis in the gut.
Using FlowVis techniques to study ocean flows

This paper presents an application of two methods — a new pseudo-LIC method and a novel streamline placement method — for improving the performance of ocean flow visualization over current methods. Instead of directly texture mapping streamlines as previous methods, the new pseudo-LIC method varies the thickness of a streamline according to its distance from its neighbors before mapping a periodic intensity onto the streamline. This method produces LIC-like image with better contrast and finer delineation. With the novel streamline placement method, topology-aware and evenly-spaced streamline placement, intuitive flow characteristics are presented with visually pleasing streamlines. First, singularities and separatrices are extracted to decompose the flow field into topological regions. Then, a preferred seeding path is selected in each region. The uniform sample points on this path are used as seeds to generate streamlines. We applied these two methods to Navy Coastal Ocean Model (NCOM) data. The resulting visualizations demonstrate the effectiveness of these two methods.
Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice.

Previously, we have shown in a model of hypersensitivity pneumonitis that Th1-biased C57BL/6 mice are susceptible and Th2-biased DBA/2 mice are resistant to disease. We also showed that this was explained in part by differential regulation of IL-12 by IL-4. For these reasons, we postulated that C57BL/6 and DBA/2 mice differentially express IL-4. In this study, we show that C57BL/6 immune cells express Th2 but not Th1 cytokines at lower levels than DBA/2 cells. We also found that C57BL/6 splenocytes exhibit decreased mRNA stability of Th2 cytokines, relative to DBA/2 splenocytes. Stability of IL-2 and IFN-γ were similar in the two strains of mice. Differences in Th2 cytokine mRNA stability between C57BL/6 and DBA/2 cells were not due to sequence polymorphism at specific regions of the IL-4/IL-13 locus. Furthermore, expression of Th1- and Th2-specific transcription factors T-bet and GATA-3, as well as the nuclear factor of activated T cells transcription factor, NFATc, was not significantly different between the two mice. Our data suggest that decreased mRNA stability of Th2 cytokines in C57BL/6 splenocytes may underlie the differential susceptibility to hypersensitivity pneumonitis between C57BL/6 and DBA/2 mice. Moreover, our results indicate that regulation of mRNA stability may serve as an important mechanism underlying Th1/Th2 immune polarization.
The Köhler effect: Motivation gains and losses in real sports groups.

Two investigations aimed to document motivation gains and losses (the Kohler effect and social-loafing effects) in real-life group work. Specifically, using archival data, motivation changes were analyzed from individual to additive group competition in collegiate swim, and high school track and field relays. Results showed that inferior group members had significantly greater motivation gains than noninferior teammates in preliminary and final swim races. Motivation gains also were significantly higher in the final compared to the preliminary race. Similar results were replicated with the track and field athletes with the weakest member of the team showing larger difference scores from individual to group competition compared to middle-ranked and higher-ranked teammates. On the whole, both studies provide ecological support for the Kohler effect, and that inferior team members showed the greatest motivation gains. No significant differences were found to support social-loafing effects within the same groups, but performances of superior group members tended to be slower.
Does Type of Pancreaticojejunostomy after Pancreaticoduodenectomy Decrease Rate of Pancreatic Fistula? A Randomized, Prospective, Dual-Institution Trial

Background Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy. There have been no large prospective randomized trials evaluating PF rates comparing invagination versus duct to mucosa pancreaticojejunostomy. We tested the hypothesis that a duct to mucosa pancreaticojejunostomy would reduce the PF rate. Study Design Between August 2006 and May 2008, 197 patients at two institutions underwent pancreaticoduodenectomy by a total of 8 experienced pancreatic surgeons as part of this prospective randomized trial (clinical trial no. NCT00359320). All patients were stratified by pancreatic texture and randomized to either an invagination or a duct to mucosa pancreaticojejunal anastomosis. Recorded variables included pancreatic duct diameter, operative time, blood loss, complications, and pathology. Primary end point was PF rate, as defined by the International Study Group on Pancreatic Fistula. Secondary end points included PF grade, postoperative length of hospital stay, other morbidities, and mortality. Results Rate of PF for the entire cohort was 17.8%. There were 23 fistulas (24%) in the duct to mucosa cohort and 12 fistulas (12%) in the invagination cohort (p Conclusions This dual-institution prospective randomized trial reveals considerably fewer fistulas with invagination compared with duct to mucosa pancreaticojejunostomy after pancreaticoduodenectomy. Results confirm increased PF rates in soft as compared with hard glands. Additional studies are needed to define the optimal technique of pancreatic reconstruction after pancreaticoduodenectomy.
Bridging the gap: A regulator of NF-κB linking inflammation and cancer

Background A close connection between inflammation and cancer has now been firmly established. While tumor initiation is typically independent of inflammatory events, immune cells infiltrating the tumor microenvironment secrete inflammatory cytokines that enhance the aberrant growth of tumor cells and thus facilitate tumor progression. Therefore, inflammation and tumor growth are usually interpreted as closely related on a systemic level but as distinct, independently regulated processes at a molecular level.
A Fluorescent Adenosine Analogue as a Substrate for an A‐to‐I RNA Editing Enzyme

Adenosine to inosine RNA editing catalyzed by ADAR enzymes is common in humans, and altered editing is associated with disease. Experiments using substrate RNAs with adenosine analogues at editing sites are useful for defining features of the ADAR reaction mechanism. The reactivity of ADAR2 was evaluated with RNA containing the emissive adenosine analogue thieno[3,4-d]-6-aminopyrimidine ((th)A). This nucleoside was incorporated into a mimic of the glutamate receptor B (GluR B) mRNA R/G editing site. We found that (th)A is recognized by AMV reverse transcriptase as A, and is deaminated rapidly by human ADAR2 to give (th)I. Importantly, ADAR reaction progress can be monitored by following the deamination-induced change in fluorescence of the (th)A-modified RNA. The observed high (th)A reactivity adds to our understanding of the structural features that are necessary for an efficient hADAR2 reaction. Furthermore, the new fluorescent assay is expected to accelerate mechanistic studies of ADARs.
A Note on Walter Block’s Defending the Undefendable

Abstract. Walter Block’s amusing and popular Defending the Undefendable offers an intentionally shocking collection of short chapters, each praising a different “rogue” of modern society—including the pimp, slumlord, and corrupt cop—from a libertarian viewpoint. However, Block’s defense of the “heroic” counterfeiter is based on faulty economic analysis and is hence completely unwarranted.
Event Sequencing as an Organizing Cultural Principle

Abstract One common cultural organizing principle is event sequencing. This article describes and illustrates two widespread examples of this kind of organization, cultural routines, and cultural templates. Cultural routines organize recurrent activities in time and space. Cultural templates rely on causally linked sequences of more abstract events to support reasoning and narrative. Why should so much of culture be organized thusly? My argument rests on evidence from childhood development and evolutionary history. Recognition of discrete events and their sequencing in routines occurs early in childhood. Although event sequencing is an ancestral trait in humans, it is the full-blown human capacity to understand how the events in such a sequence are causally linked, including intentionally linked, that finds its way into the organization of cultural templates. In taking advantage of event sequencing and causality, culture has piggybacked on human cognitive capacities. It follows that a full accounting of human culture requires recognition of the way both world and brain are organized.
Recognition memory for pictures: Dynamic vs. static stimuli

In prior research, pictorial recognition memory typically has been measured by having subjects encode static visual stimuli, such as photographs and projected photoslides. An experiment explored short-term recognition memory for the content of a 10-min segment of film. In one testing condition, 8-sec film segments derived from the study film segment and from other sections of the same film were used as targets and foils. In another testing condition, still pictures (“freeze frames”) derived from the film segment and from other portions of the film were presented as targets and foils. Control subjects saw still pictures and were tested on still targets and foils, all derived from the films. Pictorial recognition memory for dynamically presented material was significantly better than memory for the same information presented statically.
Effects of Air Pollution on Heart Rate Variability: The VA Normative Aging Study

Reduced heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with air pollution, especially fine particulate matter [< 2.5 μm in aerodynamic diameter (PM2.5)]. We examined the relationship between HRV [standard deviation of normal-to-normal intervals (SDNN), power in high frequency (HF) and low frequency (LF), and LF:HF ratio] and ambient air pollutants in 497 men from the Normative Aging Study in greater Boston, Massachusetts, seen between November 2000 and October 2003. We examined 4-hr, 24-hr, and 48-hr moving averages of air pollution (PM2.5, particle number concentration, black carbon, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide). Controlling for potential confounders, HF decreased 20.8% [95% confidence interval (CI), 4.6–34.2%] and LF:HF ratio increased 18.6% (95% CI, 4.1–35.2%) per SD (8 μg/m3) increase in 48-hr PM2.5. LF was reduced by 11.5% (95% CI, 0.4–21.3%) per SD (13 ppb) increment in 4-hr O3. The associations between HRV and PM2.5 and O3 were stronger in people with ischemic heart disease (IHD) and hypertension. The associations observed between SDNN and LF and PM2.5 were stronger in people with diabetes. People using calcium-channel blockers and beta-blockers had lower associations between O3 and PM2.5 with LF. No effect modification by other cardiac medications was found. Exposures to PM2.5 and O3 are associated with decreased HRV, and history of IHD, hypertension, and diabetes may confer susceptibility to autonomic dysfunction by air pollution.
Contribution of excessive alcohol consumption to deaths and years of potential life lost in the United States.

Introduction Excessive alcohol consumption is a leading cause of premature mortality in the United States. The objectives of this study were to update national estimates of alcohol-attributable deaths (AAD) and years of potential life lost (YPLL) in the United States, calculate age-adjusted rates of AAD and YPLL in states, assess the contribution of AAD and YPLL to total deaths and YPLL among working-age adults, and estimate the number of deaths and YPLL among those younger than 21 years.
Approximation of the error caused by the radio deviation in the automatic direction finder

Summary form only given. For the compensation of the error caused by the radio deviation in the automatic direction finder a mechanical compensator or quadrantal corrector is used. A systematic characteristic of this error allows the approximation and electronic compensation. Different methods for the approximation are explored. The result is that the discrete Fourier transform (DFT) is the best method. A structural scheme for the electronic compensator of the error caused by the radio deviation is offered.
Resonant scattering of edge waves by longshore periodic topography: finite beach slope

The resonant scattering of low-mode progressive edge waves by small-amplitude longshore periodic depth perturbations superposed on a plane beach has recently been investigated using the shallow water equations (Chen & Guza 1998). Coupled evolution equations describing the variations of edge wave amplitudes over a finite-size patch of undulating bathymetry were developed. Here similar evolution equations are derived using the full linear equations, removing the shallow water restriction of small (2N + 1)θ, where N is the maximum mode number considered and θ is the unperturbed planar beach slope angle. The present results confirm the shallow water solutions for vanishingly small (2N + 1)θ and allow simple corrections to the shallow water results for small but finite (2N + 1)θ. Additionally, multi-wave scattering cases occurring only when (2N + 1)θ = O(1) are identified, and detailed descriptions are given for the case involving modes 0, 1, and 2 that occurs only on a steep beach with θ = π/12.
DNA bending and twisting properties of integration host factor determined by DNA cyclization.

The binding of many proteins to DNA is profoundly affected by DNA bending, twisting, and supercoiling. When protein binding alters DNA conformation, interaction between inherent and induced DNA conformation can affect protein binding affinity and specificity. Integration host factor (IHF), a sequence-specific, DNA-binding protein of Escherichia coli, strongly bends the DNA upon binding. To assess the influence of inherent DNA bending on IHF binding, we took advantage of the high degree of natural static curvature associated with an IHF site on a 163-bp minicircle and measured the binding affinity of IHF for its recognition site contained on this DNA in both circular and linear form. IHF showed a higher affinity for the circular form of the DNA when compared to the linear form. In addition, the presence of IHF during DNA cyclization changed the topology of cyclization products and their ability to bind IHF, consistent with IHF untwisting DNA. These results show that inherent DNA conformation anisotropy is an important determinant of IHF binding affinity and suggests a mechanism for modulation of IHF activity by local DNA conformation.
Handling churn in a DHT

This paper addresses the problem of churn--the continuous process of node arrival and departure--in distributed hash tables (DHTs). We argue that DHTs should perform lookups quickly and consistently under churn rates at least as high as those observed in deployed P2P systems such as Kazaa. We then show through experiments on an emulated network that current DHT implementations cannot handle such churn rates. Next, we identify and explore three factors affecting DHT performance under churn: reactive versus periodic failure recovery, message timeout calculation, and proximity neighbor selection. We work in the context of a mature DHT implementation called Bamboo, using the ModelNet network emulator, which models in-network queuing, cross-traffic, and packet loss. These factors are typically missing in earlier simulation-based DHT studies, and we show that careful attention to them in Bamboo's design allows it to function effectively at churn rates at or higher than that observed in P2P file-sharing applications, while using lower maintenance bandwidth than other DHT implementations.
Rethinking the role of the rTPJ in attention and social cognition in light of the opposing domains hypothesis: findings from an ALE-based meta-analysis and resting-state functional connectivity

The right temporo-parietal junction (rTPJ) has been associated with two apparently disparate functional roles: in attention and in social cognition. According to one account, the rTPJ initiates a “circuit-breaking” signal that interrupts ongoing attentional processes, effectively reorienting attention. It is argued this primary function of the rTPJ has been extended beyond attention, through a process of evolutionarily cooption, to play a role in social cognition. We propose an alternative account, according to which the capacity for social cognition depends on a network which is both distinct from and in tension with brain areas involved in focused attention and target detection: the default mode network (DMN). Theory characterizing the rTPJ based on the area's purported role in reorienting may be falsely guided by the co-occurrence of two distinct effects in contiguous regions: activation of the supramarginal gyrus (SMG), associated with its functional role in target detection; and the transient release, during spatial reorienting, of suppression of the angular gyrus (AG) associated with focused attention. Findings based on meta-analysis and resting functional connectivity are presented which support this alternative account. We find distinct regions, possessing anti-correlated patterns of resting connectivity, associated with social reasoning (AG) and target detection (SMG) at the rTPJ. The locus for reorienting was spatially intermediate between the AG and SMG and showed a pattern of connectivity with similarities to social reasoning and target detection seeds. These findings highlight a general methodological concern for brain imaging. Given evidence that certain tasks not only activate some areas but also suppress activity in other areas, it is suggested that researchers need to distinguish two distinct putative mechanisms, either of which may produce an increase in activity in a brain area: functional engagement in the task vs. release of suppression.
Valve morphology of four species of Frustulia (Bacillariophyta), including two described as new

We present here descriptions and light and scanning electron micrographs for four species of Frustulia . Two of the species, F. rexii and F. cf. saxonica , were collected from the northern portion of the lower peninsula of Michigan, U.S.A. The third, F. cf. krammeri , can be found on at least two islands in Hawaii, U.S.A., while the fourth, F. lacrima , was collected from lakes in Brasil. We refer to the four species as “typical” Frustulia because their longitudinal rib systems resemble that seen in the generitype, F. saxonica Rabenh., and they share other valve features with this group. The new species differ from congeners in valve shape, organization and density of the striae, and degree of physical integration between the longitudinal ribs and helictoglossae. In both well-studied (Michigan) and less-studied (Hawaii, Brasil) parts of the world it appears there is more work to do to document the diversity of the genus Frustulia.
Robotic Neuromuscular Facilitation for Regaining Neural Activation in Hemiparetic Limbs

This paper introduces an effective engineered rehabilitation system for understanding and inducing functional recovery of hemiparetic limbs based on the concept of timing-dependent induction of neural plasticity. Limb motor function is commonly impaired after neurologic injury such as stroke, with hemiparesis being one of the major impairments. In an emerging unique intervention for hemiparesis, named repetitive facilitation exercise, or RFE, a therapist manually applies brief mechanical stimuli to the peripheral target muscles (e.g., tapping, stretching of tendon/muscle) immediately before a patient intends to produce a movement with the muscle. The practice of this rehabilitation procedure by a skilled therapist often leads to dramatic rehabilitation outcomes. However, unskilled therapists, most likely due to the inaccuracy of the timing of peripheral stimulation in reference to the intention of movement (i.e. motor command), are unable to recreate the same rehabilitation results. Robotic rehabilitation, on the other hand, can improve the reliability and efficacy of the operation by satisfying the timing precision required by the therapy. This study demonstrates the use of a pneumatically-driven MRI-compatible robot for RFE assessment. The pressure dynamics of the system is studied for an accurate estimation on the time of response of the robot. The required temporal precision of the therapy is obtained and the use of the device is validated through experiments on a human subject.Copyright © 2015 by ASME
Determination of Myofilament Calcium Distributions from Electron Probe X-ray Microanalysis Images

The quantity and spatial distribution of calcium bound to myofilaments is of considerable interest to physiologists studying the regulation of contraction in striated muscle, but few techniques allow these distributions to be directly measured. Methods are described here by which such data can be derived from electron probe X-ray microanalysis (EPXMA) images. Combination of data from multiple half sarcomeres improves the signal-to-noise level and allows assessment of variation between half sarcomeres. Profiles of calcium counts, calcium counts normalized to local bremstrahlung counts, and calcium counts normalized to the average bremstrahlung counts for the entire half sarcomere provide differing but complementary information. Such data help to identify and characterize spatial variations in Ca binding to regulatory proteins in muscle.
Design Approach for A Customer Care IVRU: Conversational Prompting Style Compared to Directed Dialog

Interactive Voice Response Units (IVRUs) answer the phones more often than people do in many business domains, including Telecommunication, Personal Finance, Utilities, etc. This paper presents the results of a research study that Sprint initiated to solve a specific business problem within its IVRU. Two design approaches were assessed, pitting a Natural Language with Directed Dialog Fallback structure versus a traditional Directed Dialog framework. Key measurements included task completion and efficiency. The Natural Language with Directed Dialog Fallback design slightly outperformed the Directed Dialog approach by providing a compelling hybrid of two archetypal IVRU approaches.
Cerebrospinal Fluid and Interstitial Fluid Motion via the Glymphatic Pathway Modelled by Optimal Mass Transport

It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the `glymphatic pathway' plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs [1,2]. It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through peri-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns. We have accordingly analyzed a series of MRI images, taken at different times, of the brain of a live rat, which was injected with a paramagnetic tracer into the CSF via the lumbar intrathecal space of the spine. Our goal is twofold: (a) find glymphatic (tracer) flow directions in the live rodent brain; and (b) provide a model of a (healthy) brain that will allow the prediction of tracer concentrations given initial conditions. We model the liquid flow through the brain by the diffusion equation. We then use the Optimal Mass Transfer (OMT) approach [3] to model the glymphatic flow vector field, and estimate the diffusion tensors by analyzing the (changes in the) flow. Simulations show that the resulting model successfully reproduces the dominant features of the experimental data.
Analysis on clinical application of self-made preparation in our hospital

Objective To analyze the role of hospital preparations in our hospital clinical drug use,evaluate the importance of its existence. Methods Summing up our varieties of hospital preparations and statistical analysis of the clinical usage from January 1,2010 to December 31,2012. Results Number of hospital preparations varieties slightly reduced,total sales and sales rise year by year. Hospital preparations sales accounted for about 7. 5% of total drug sales. Conclusion Hospital preparations were necessary to clinical diagnosis and treatment,it was indispensable.
Molecular and gene therapies for wound repair

Abstract: The basic concept of gene therapy is to introduce into a cell a therapeutic gene whose expression can offer a transient advantage for tissue growth and regeneration or lead to the cure of a disease. In this chapter, we look at current gene therapy for cutaneous wound healing, focusing on the most commonly used genes for wound healing enhancement. We have included a short account of the important ethical issues related to gene therapy and conclude with a discussion on future prospects of gene therapy.