Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and characterization of the type-IVA cyclic AMP-specific phosphodiesterase RD1 as a membrane-bound protein expressed in cerebellum.

An antiserum was generated against a dodecapeptide whose sequence is found at the C-terminus of a cyclic AMP (cAMP)-specific, type-IVA phosphodiesterase encoded by the rat 'dunc-like' cyclic AMP phosphodiesterase (RD1) cDNA. This antiserum identified a single approximately 73 kDa protein species upon immunoblotting of cerebellum homogenates. This species co-migrated upon SDS/PAGE with a single immunoreactive species observed in COS cells transfected with the cDNA for RD1. Native RD1 in cerebellum was found to be predominantly (approximately 93%) membrane-associated and could be found in isolated synaptosome populations, in particular those enriched in post-synaptic densities. Fractionation of lysed synaptosomes on sucrose density gradients identified RD1 as co-migrating with the plasma membrane marker 5'-nucleotidase. Laser scanning confocal and digital deconvolution immunofluorescence studies done on intact COS cells transfected with RD1 cDNA showed RD1 to be predominantly localized to plasma membranes but also associated with the Golgi apparatus and intracellular vesicles. RD1-specific antisera immunoprecipitated phosphodiesterase activity from solubilized cerebellum membranes. This activity had the characteristics expected of the type-IV cAMP phosphodiesterase RD1 in that it was cAMP specific, exhibited a low Km cAMP of 2.3 microM, high sensitivity to inhibition by 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) (Ki approximately 0.7 microM) and was unaffected by Ca2+/calmodulin and low concentrations of cyclic GMP. The phosphodiesterase activities of RD1 solubilized from both cerebellum and transfected COS cell membranes showed identical first-order thermal denaturation kinetics at 50 degrees C. Native RD1 from cerebellum was shown to be an integral protein in that it was solubilized using the non-ionic detergent Triton X-100 but not by either re-homogenization or high NaCl concentrations. The observation that hydroxylamine was unable to cause the release of RD1 from either cerebellum or COS membranes and that [3H]palmitate was not incorporated into the RD1 protein immunoprecipitated from COS cells transfected with RD1 cDNA, indicated that RD1 was not anchored by N-terminal acylation. The engineered deletion of the 25 residues forming the unique N-terminal domain of RD1 caused both a profound increase in its activity (approximately 2-fold increase in Vmax) and a profound change in intracellular distribution. Thus, immunofluorescence studies identified the N-terminal truncated species as occurring exclusively ion the cytosol of transfected COS cells. The cDNA for RD1 thus appears to encode a native full-length type-IVA phosphodiesterase that is expressed in cerebellum. (ABSTRACT TRUNCATED AT 400 WORDS)
The Charnley-Hastings Hemiarthroplasty for Fractures of the Femoral Neck with Special Reference to Complications

We report a retrospective study of the incidence of major complications following Charnley-Hastings bipolar hemiarthroplasty in 117 patients with 120 fractures of the femoral neck. Primary hemiarthroplasty (n=40) was used for irreducible or old fractures and secondary hemiarthroplasty (n=80) for fractures with disturbed healing. The mean age was 80 (54-95) years. The mean follow-up was 34 (0-149) months. There was no major complication in 87.2 percent. Mortality was 10.3 percent after 6 months and 13.7 percent after one year. Dislocation occurred in 7.5 percent, prosthetic loosening in 4.2 percent, acetabular fracture and deep infection in 0.8 percent respectively. Reoperation was required in 7.5 percent: open reduction after dislocation (2.5 percent), conversion to a Charnley total hip arthroplasty (3.3 percent), Girdlestone arthroplasty (0.8 percent) and exchange of a loose femoral component (0.8 percent). We conclude that the selective use of bipolar hemiarthroplasty for fractures of the femoral neck carries few major complications. Patient selection must be strict in order to reduce the risk of dislocation.
Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae*

The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC50 = 4.6 ± 0.4 ng/ml) and crustaceans (Artemia nauplii LD50 = 10 ± 2 μg/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity against ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-Å resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.
Visual Performance of a Multifocal Contact Lens versus Monovision in Established Presbyopes

Purpose To compare subjective and objective visual performance of the Air Optix Aqua Multifocal lens to monovision in a group of subjects requiring a medium level of reading-addition power. Methods Fifty participants with reading additions between 1.25 and 2.00 diopters (inclusive) were randomized into a prospective, crossover clinical trial. They wore monovision and multifocals for 2 weeks in a randomized order. High- and low-contrast logMAR (logarithm of the minimum angle of resolution) acuity and stereopsis were measured at the beginning and end of each period. During each phase, participants performed specific tasks followed by subjective rating surveys and also completed satisfaction rating surveys on days 3, 7, and 12; all were transferred in real time using BlackBerry smartphones. A general rating survey was completed at the dispensing and 2-week visits. Results Forty-nine participants completed the study (mean age, 52 years). Distance and near high- and low-contrast acuities were significantly better (p < 0.05) with monovision at all visits. High-contrast intermediate acuity was only better (p < 0.05) with multifocals after 2 weeks. Stereopsis was equivalent after 2 weeks, but better (p < 0.05) with multifocals at dispensing. Subjective ratings were generally equivalent between modalities although there was a trend for multifocals to be rated higher for focus changing and driving, whereas monovision tended to be rated higher for near tasks. For both corrections, the satisfaction survey showed no significant change between days 3, 7, and 12, and the general survey showed that comfort was maintained but subjective vision ratings decreased significantly over the 2 weeks. Twenty-five participants (51%) preferred multifocals, 18 (37%) preferred monovision, and the remaining 6 (12%) declared both unacceptable. Conclusions In this cohort, distance and near acuities were better with monovision, whereas the subjective ratings tended to favor the Air Optix Aqua Multifocal, with the exception of near performance. Preference was statistically similar between both corrections, with a trend toward preferring the multifocal.
Don't think of a white bear: An fMRI investigation of the effects of sequential instructional sets on cortical activity in a task‐switching paradigm

Using functional magnetic resonance imaging (fMRI), we investigated processes involved in switching between two ongoing tasks, thought to be paradigmatic of executive control processes. Subjects were considerably slower and less accurate when switching between two tasks than when repeatedly carrying out one task, so‐called “switch costs. ” Switch costs, however, generally occur only when more than one task is associated with each stimulus type. This has led to the surmise that switch costs may be due largely to ongoing interference from previously learned stimulus‐response (S‐R) associations, which are no longer relevant for the task at hand. We used a paradigm that specifically assessed this hypothesis and investigated three stages. In Stage 1, a single task was carried out with each stimulus type; in Stage 2, a second novel task was introduced for each stimulus type; and in Stage 3, subjects reverted to carrying out solely the original tasks (as in Stage 1). In Stage 1, only one task was associated with each stimulus type, whereas two tasks were associated with each stimulus type in Stages 2 and 3. We compared images obtained during Stage 3 to those obtained during Stage 1 and show that during Stage 3, there was robust activation in the network of areas associated with the Stage 2 tasks, even though these tasks were no longer relevant. Our data strongly suggest that switch costs may derive largely from continued activation of areas associated with carrying out the now‐irrelevant task(s). We posit that a large component of executive control processes involves resolution of competition between potentially relevant tasks. Our data also revealed widespread activation of a frontoparietal network of areas, and we discuss how this network might be involved in mediating this competition. Hum. Brain Mapping 21:279–297, 2004. © 2004 Wiley‐Liss, Inc.
Key Management for Multicast: Issues and Architectures

This report contains a discussion of the difficult problem of key management for multicast communication sessions. It focuses on two main areas of concern with respect to key management, which are, initializing the multicast group with a common net key and rekeying the multicast group. A rekey may be necessary upon the compromise of a user or for other reasons (e.g., periodic rekey). In particular, this report identifies a technique which allows for secure compromise recovery, while also being robust against collusion of excluded users. This is one important feature of multicast key management which has not been addressed in detail by most other multicast key management proposals [1,2,4]. The benefits of this proposed technique are that it minimizes the number of transmissions required to rekey the multicast group and it imposes minimal storage requirements on the multicast group.
Cloning, characterization, and functional expression of acs, the gene which encodes acetyl coenzyme A synthetase in Escherichia coli

Acetyl coenzyme A synthetase (Acs) activates acetate to acetyl coenzyme A through an acetyladenylate intermediate; two other enzymes, acetate kinase (Ack) and phosphotransacetylase (Pta), activate acetate through an acetyl phosphate intermediate. We subcloned acs, the Escherichia coli open reading frame purported to encode Acs (F. R. Blattner, V. Burland, G. Plunkett III, H. J. Sofia, and D. L. Daniels, Nucleic Acids Res. 21:5408-5417, 1993). We constructed a mutant allele, delta acs::Km, with the central 0.72-kb BclI-BclI portion of acs deleted, and recombined it into the chromosome. Whereas wild-type cells grew well on acetate across a wide range of concentrations (2.5 to 50 mM), those deleted for acs grew poorly on low concentrations (< or = 10 mM), those deleted for ackA and pta (which encode Ack and Pta, respectively) grew poorly on high concentrations (> or = 25 mM), and those deleted for acs, ackA, and pta did not grow on acetate at any concentration tested. Expression of acs from a multicopy plasmid restored growth to cells deleted for all three genes. Relative to wild-type cells, those deleted for acs did not activate acetate as well, those deleted for ackA and pta displayed even less activity, and those deleted for all three genes did not activate acetate at any concentration tested. Induction of acs resulted in expression of a 72-kDa protein, as predicted by the reported sequence. This protein immunoreacted with antiserum raised against purified Acs isolated from an unrelated species, Methanothrix soehngenii. The purified E. coli Acs then was used to raise anti-E. coli Acs antiserum, which immunoreacted with a 72-kDa protein expressed by wild-type cells but not by those deleted for acs. When purified in the presence, but not in the absence, of coenzyme A, the E. coli enzyme activated acetate across a wide range of concentrations in a coenzyme A-dependent manner. On the basis of these and other observations, we conclude that this open reading frame encodes the acetate-activating enzyme, Acs.
Reliability of ophthalmic accident and emergency referrals: a new role for the emergency nurse practitioner?

Background and objectives: Annual attendances at the accident and emergency (A&E) department of St Bartholomew’s and The Royal London NHS Trust exceed 100 000 people of which 6% are ophthalmic. This study evaluated the accuracy of eye referrals from A&E senior house officers (SHOs) and emergency nurse practitioners (ENPs) and the impact any inaccuracies may have had on out of hours work. Methods: Over a four week period a record of all referrals from the A&E department was made. The doctor receiving the referral made a note of clinical variables as reported by the referring clinician. When the patient was subsequently reviewed by an ophthalmologist, a record was again made of these findings. Any discrepancies were recorded. Results: A total of 67 patients were recruited. ENPs were found to be consistently more accurate than SHOs in every aspect of the assessment, most notably in visual acuity (p = 0.0029), and provisional diagnosis (p = 0.012). Furthermore, had the examination findings been accurate, 58% of all SHO referrals seen after hours would have been triaged to the next available clinic but only 10% of ENP referrals could have been seen at the next clinic session (p = 0.027). Conclusion: This study found ENPs to be more accurate than A&E SHOs in history taking, recording visual acuity, describing ocular anatomy, and making provisional diagnoses. A significant reduction in out of hours ophthalmic workload may be achieved in the authors’ unit if ENPs were to see all eye emergencies.
Projections of U.S. Edentulism Prevalence Following 5 Decades of Decline

After decades of decline in prevalence of complete tooth loss (edentulism), the trend continues to be misinterpreted, producing flawed projections and misdirected health goals. We investigated population trends in edentulism among U.S. adults aged ≥15 yr by creating time-series data from 5 national cross-sectional health surveys: 1957-1958 (n ≈ 100,000 adults), 1971-1975 (n = 14,655 adults), 1988-1998 (n = 18,011 adults), 1999-2002 (n = 12,336 adults), and 2009-2012 (n = 10,522 adults). Birth cohort analysis was used to isolate age and cohort effects. Geographic and sociodemographic variation in prevalence was investigated with a sixth U.S. survey of 432,519 adults conducted in 2010. Prevalence through 2050 was projected with age-cohort regression models using Monte-Carlo simulation of prediction intervals. Across the 5-decade observation period, edentulism prevalence declined from 18.9% in 1957-1958 (95% confidence limits: 18.4%, 19.4%) to 4.9% in 2009-2012 (95% confidence limits: 4.0%, 5.8%). The most influential determinant of the decline was the passing of generations born before the 1940s, whose rate of edentulism incidence (5%-6% per decade of age) far exceeded later cohorts (1%-3% per decade of age). High-income households experienced a greater relative decline, although a smaller absolute decline, than low-income households. By 2010, edentulism was a rare condition in high-income households, and it had contracted geographically to states with disproportionately high poverty. With the passing of generations born in the mid-20th century, the rate of decline in edentulism is projected to slow, reaching 2.6% (95% prediction limits: 2.1%, 3.1%) by 2050. The continuing decline will be offset only partially by population growth and population aging such that the predicted number of edentulous people in 2050 (8.6 million; 95% prediction limits: 6.8 million, 10.3 million) will be 30% lower than the 12.2 million edentulous people in 2010.
Framing Contests: Strategy Making Under Uncertainty

I develop a model of framing contests to elucidate how cognitive frames influence organizational strategy making. By using ethnographic techniques to study the day-to-day practices of strategy making in one firm, I examine the ways actors attempted to transform their own cognitive frames of a situation into predominant frames through a series of interactions. Frames are the means by which managers make sense of ambiguous information from their environments. Actors each had cognitive frames about the direction the market was taking and about what kinds of solutions would be appropriate. Where frames about a strategic choice were not congruent, actors engaged in highly political framing practices to make their frames resonate and to mobilize action in their favor. Those actors who most skillfully engaged in these practices shaped the frame that prevailed in the organization. This framing perspective suggests that frames are not only instrumental tools for the ex post justification of actions taken through power, but rather are an ex ante part of the political process that produces decisions. Uncertainty opens up the possibility for new actors to gain power, and contesting frames is a way of changing the power structures in the organization. A principal contribution of the framing contests model is to locate a middle ground between cognitive and political models of strategy making, one in which frames are both constraints and resources and outcomes can be shaped by purposeful action and interaction to make meaning.
Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome

Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies.
Inequality and Decision Making: Imagining a New Line of Inquiry

The substantial increase in inequality in the United States over the past three decades has provoked considerable debate, with some analysts characterizing rising inequality as among the greatest threats facing the nation and others dismissing it as little more than a hiccup – or even celebrating it as a favorable development – in the progress of American capitalism. Despite numerous claims in popular venues that high inequality has slowed growth, precipitated financial instability, and profoundly distorted the nation’s political system, our review of the literature finds no academic consensus on the consequences of inequality for the health of the economy or the democracy, or for nearly any other macro-level outcome. With the academic community reaching inconclusive and conflicting findings, we suggest that careful empirical study of possible mechanisms by which income inequality may exert macro-level effects is warranted. We suggest further that that one potential mechanism that may be especially worthy of investigation relates to possible effects of high or rising inequality on individual decision making. Drawing on nascent research, we examine a handful of pathways through which inequality may plausibly influence individual decisions. Finally, we propose ways that these and other pathways might be productively explored and assessed through behavioral experiments. By bringing together what are today two separate areas of research – decision making and inequality (or social disparity) – this new line of inquiry could help to break the stalemate that has, until now, characterized the study of inequality and its consequences.
Influence of back ground plane on new radio frequency monochip systems

Every high frequency circuits need inductors for proper work. This is more and more true with new radio-frequency MOS transistors systems. But with the increase in frequency, lower inductors are required and MOS transistors offer less gain. Radio-frequency circuits in MOS technology are also obedient to the layout of low inductance high quality factor inductors. It has been shown that they can be better realized by microstrips. However, classical MOS digital technologies have no back ground plane under the substrate. This article analyzes the influence of parasitic back ground planes in the case of an often used coplanar solution: coplanar waveguide.
Arabidopsis TCP Transcription Factors Interact with the SUMO Conjugating Machinery in Nuclear Foci

In Arabidopsis more than 400 proteins have been identified as SUMO targets, both in vivo and in vitro. Among others, transcription factors (TFs) are common targets for SUMO conjugation. Here we aimed to exhaustively screen for TFs that interact with the SUMO machinery using an arrayed yeast two-hybrid library containing more than 1,100 TFs. We identified 76 interactors that foremost interact with the SUMO conjugation enzyme SCE1 and/or the SUMO E3 ligase SIZ1. These interactors belong to various TF families, which control a wide range of processes in plant development and stress signaling. Amongst these interactors, the TCP family was overrepresented with several TCPs interacting with different proteins of the SUMO conjugation cycle. For a subset of these TCPs we confirmed that the catalytic site of SCE1 is essential for this interaction. In agreement, TCP1, TCP3, TCP8, TCP14, and TCP15 were readily SUMO modified in an E. coli sumoylation assay. Strikingly, these TCP-SCE1 interactions were found to redistribute these TCPs into nuclear foci/speckles, suggesting that these TCP foci represent sites for SUMO (conjugation) activity.