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The crystal structure of integration host factor (IHF) complexed with DNA shows how a small heterodimeric protein can induce a big bend in DNA. IHF exerts leverage in the minor groove and wraps DNA around the body of the protein, providing another example of sequence-specific recognition of the minor groove.
OBJECTIVES: To identify the issues or problems that current and aspiring U.S. Department of Defense (DoD) pharmacy executives will face in the future and to define the skills, knowledge, and abilities (SKAs) required to successfully address these issues. DESIGN: Delphi method for executive decision making. SETTING: DoD. PARTICIPANTS: Ninety-three pharmacists serving in the military grades of lieutenant colonel/commander and colonel/captain, as well as pharmacists selected for promotion to those grades. INTERVENTIONS: iterations of the Delphi method for executive decision making separated by an expert panel content analysis. MAIN OUTCOME MEASURES: Round 1--participants identified five major issues believed to be of greatest importance to pharmacy executives and reported specific SKAs that might be needed to successfully manage those issues. An expert panel sorted these issues into meaningful domains, then provided an appropriate title for each domain. Round 2--on a 7-point scale, respondents rated the SKA items according to their assessment of how much a future DoD pharmacy executive would need each SKA. RESULTS: Response rates were 44.1% and 46.2% for Delphi rounds 1 and 2, respectively. The first round generated 62 unique issues facing pharmacy executives. The expert panel reviewed and sorted the issues into eight domains and selected an appropriate title for each domain. The domains identified by the panel were human resources, pharmacy operations/business practices, information management and technology, financial resources, formulary management, drug therapy management, pharmacy benefit management, and leadership. During round 2, 73.3% of the top 15 rated SKAs came from the drug therapy management, leadership, and formulary management domains. The three highest-rated SKAs were "ability to see the big picture," "ability to build strong relations with medical staffs," and "skills in both writing and verbal communication." CONCLUSION: The issues facing future DoD pharmacy executives will require them to expand their clinical abilities as well as their ability to collaborate and communicate with other professionals.
The algorithm of back projection with filtration for exponential Radon transform leads to strong distortion for big diameter objects. The main reason for this distortion is mainly the exponential increase of errors in the quadrature formula for a weighed back projection operator. So it is sometimes more convenient to use the back Radon transform R-1 and then to correct the result, taking into account attenuation. For this purpose, the approximation formulas are given, which connect f and R-1 R mu f. An appropriate iteration reconstruction algorithm is also considered. Application exponential Radon identities for projection data analysis are also discussed.
OBJECTIVE: To observe the effect of the Niaoduqing Tablet(NDT) on the diuresis in normal rats and the hemorheology in rats of blood stasis and compare it with the Niaoduqing Granule(NDG), so as to provide some laboratory data for the clinic application and innovation of the dosage forms. METHOD: Diuretic effect of the NDT on experimental rats burthened with 1% Sodium deoxycholate was observed by using the metabolize cage examination. The changes of whole blood and plasma viscosity in the blood-stasis rat-model were measured with Viscometer-R80. Plasma was separated and fibrinogen measured by using the turbidimetric method. RESULT: Every dose of NDT had the diuretic effect on experiment rats, but only the big and middle dose increasing the urine quantity in 6 hours had the significance. Each dose could reduce the viscosity of whole blood and the fibrinogen in the blood-stasis rat model, and had the superiority to NDG. CONCLUSIONS: NDT has the diuretic effect and can ameliorate the hemorheology in the blood-stasis rat model, which may delay the course of the chronic renal failure (CRF).
The clinical findings in 183 post partum periods of dairy cows from an experimental herd are reported. Sixty-nine, 30, 46, and 38 post partum periods of the Swedish Red and White Breed, the Swedish Friesian Breed, crosses between these two breeds, and the Swedish Jersey Breed, respectively, were followed by clinical examination at 10-day intervals until first service. Heat detection was done three times daily and plasma progesterone assay at 10-day intervals. The highest occurrence of big follicles (12-15 mm) was between 21-30 days, coinciding with the time of first ovulation. Fifty percent of the cows had the 1st, 2nd and 3rd ovulation at 17, 36 and 56 days post partum, respectively, and the first, second and third ovulations came at 21.2, 39.1 and 58.3 days on average, with significant differences between parities and breeds. The first two oestrous cycles lasted 17.5 +/- 5.6 and 20.8 +/- 2.1 days without differences due to parity and breeds. The data indicate a complete uterine involution between 41 and 50 days post partum.
Two studies suggest a possible interaction among sex, motor dominance, and vibrotactile threshold for the great toe and index finger. In study 1 a forced-choice procedure with the Vibratron II (Physitemp Instruments, Inc.) was used; a significant interaction between sex and foot dominance for vibratory threshold was noted with no main effects for the great toe. The greatest difference between men and women was on the nondominant side on the foot. Study 2 replicated Study 1 using the index finger as well as the great toe and used the Semmes. Weinstein monofilament test for a cross-modal comparison. A method of limits procedure was used to increase the generalizability of the data. A similar interaction was found between sex and motor dominance for the index finger but not the great toe. This was attributed to skewing of data for the toe. No effects were found for the Semmes-Weinstein test. Possible usefulness in detecting neuropathies is considered. Larger normative studies including variables such as age, height, and weight are required for generalizable conclusions.
The latest numbers on salaries and bonuses are in from the Hay Group, and it's good news from a compensation standpoint: pay for everyone, from executives to nurses, is going up. But satisfaction on the job remains low and the workforce shortage is severe, leading to the question: does more pay make everybody happy? If not, why not?
This study aims to identify genetically diverged clone mates in apomictic dandelions. Clone mates are defined as individuals that may have diverged as a result of mutation accumulation and that have undergone only clonal reproduction since their most recent common ancestor. Based on distinctive morphology and an aberrant and rare chloroplast haplotype, northwest European individuals of Taraxacum section Naevosa are well suited for the detection of clonal lineages in which mutation has occurred. In the case of strictly clonal reproduction, nuclear genetic variability was expected to be hierarchically organized. Nucleotide polymorphisms in internal transcribed spacer (ITS) sequences, however, were incompatible with a clonal structure of the Norwegian individuals, probably due to persistent ancestral polymorphisms that pre-date the origin of the Naevosa clone. This interpretation is supported by the presence of ITS variants in section Naevosa that were also found in distantly related dandelions. In contrast to the ITS sequence data, amplified fragment length polymorphisms (AFLPs), isozymes and microsatellites strongly supported the contention of prolonged clonal reproduction and mutation accumulation in Norwegian Naevosa. Because these markers are generally considered to be more variable and more rapidly evolving than ITS sequences, mutations in these markers probably evolved after the origin of the clone. Within the Norwegian clone, a surprising number of markers distinguished the clone mates. As a consequence, incorporation of mutation in the detection of clone mates is anticipated to have a big impact on estimates of size, geographical range and age of clones as well as on experimental designs of studies of clonal plants.
Today a company is not considered environmentalist unless it moves beyond mere compliance with government regulations to behavior its competitors, and even customers, do not expect. How should it set its agenda? Author Art Kleiner proposes that, to be green, a company must ask three questions: What products should we bring to market? How much disclosure of pollution information should we support? And how can we reduce waste at its source? These questions can't be answered, Kleiner says, unless managers insist on sustainable growth. In this sense, a big investment in environmentalism is like a big one in R&D--both presuppose patient capital and managerial maturity. What are green products? Kleiner cautions against giving in to misinformed public opinion--as McDonald's did in giving up its styrene "clamshells," which were more recyclable than the composite papers it switched to. Rather, companies should rely on literature that analyzes the product life cycle. As for public disclosure, the benefits may be unexpected. Federal legislation requiring companies to report the emission of potentially hazardous waste to a central data bank has not made environmentalists attack them. Rather, it has forced companies to learn what chemicals they inadvertently produce and how much--knowledge that helps them improve production processes. Sharing it helps ecological researchers study the combined effects of plant emissions. As for pollution prevention, Kleiner notes the analogy to quality and observes that it is better to design harmful waste products out of the system than catch them at the end of the line.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate the prevalence of diabetes in a rural community, 589 subjects in Laurino, Southern Italy, were submitted to a 50 g oral glucose tolerance test. Two hours later, blood glucose levels revealed 453 normal subjects, 36 diabetics and 100 borderline subjects. The borderline subjects were re-examined with 75 g OGTT and, according to criteria recommended by the National Diabetes Data Groups (NDDG), 29 subjects were found normal, 35 with impaired glucose tolerance (IGT) and 36 with diabetes. Final figures showed 72 diabetics (12.2%) and 35 IGT cases (5.9%). Obesity appeared strongly related to diabetes (p less than 0.05 in males and p less than 0.01 in females 40 years old and over). Diabetes was more prevalent in subjects with a positive family history (p less than 0.01). No significant difference in number was observed between male and female diabetics, nor between big babies delivered by normal women and big babies by diabetic women. The high diabetes prevalence might be partly explained by the changes created by an industrially-established dietetic influence on the rural communities in Southern Italy.
Endothelin (ET) is a 21-residue potent vasoconstrictive peptide produced by vascular endothelial cells and formed from its precursor, big endothelin (big ET), by endothelin-converting enzyme (ECE). This paper describes the cloning and functional expression of a cDNA encoding a human ECE from human umbilical vein endothelial cells (HUVEC). Human ECE consists of 758 amino acid residues and has high homology to rat and bovine ECE. Immunoblot analysis using a monoclonal antibody risen against rat lung ECE showed the presence of immunoreactive protein in membrane fraction prepared from both HUVEC and COS-1 cells transfected with human ECE cDNA. Both COS-1 cells expressing human ECE and its membrane fraction converted big ET-1 most efficiently among big ETs.
INTRODUCTION: Of all forms of stroke, spontaneous intracerebral haemorrhage (ICH) causes the highest morbidity and mortality. The Surgical Trial in Intracerebral Haemorrhage (STICH) found no difference in outcomes between patients randomized to surgical or conservative treatment. PATIENTS AND METHODS: Of 530 patients randomized to initial conservative treatment, 140 crossed over to surgery. This study examines the variables associated with crossover. RESULTS: Dominant features of the crossover group were: male, (p = 0.04), right-sided clot (p = 0.03), lobar clot (p = 0.003), clot volume (median 64 mL for crossovers vs. 38 mL for others, p < 0.00001), midline shift (median 6 mm for crossovers vs. 3 mm for others, p < 0.00001), superficial clot (median 1.3 mm for crossovers vs. 11.5 mm for others, p < 0.00001), and randomization within 12 hours of ictus (p < 0.0005). Thalamic location (p = 0.002) was under-represented. Intraventricular haemorrhage, hydrocephalus, and focal deficits were not associated with crossover. Craniotomy was the method of evacuation in 85% of crossover patients. CONCLUSIONS: Crossover to surgery was more likely when ICH had these features: Right side, lobar location, superficial, large volume, big shift, and early randomization. Crossovers formed a worse prognostic group compared to non-crossovers. Surgery did not affect trial results, which were analyzed by intention-to-treat.
A method of assessing biological age by the application of principal component analysis is reported. Healthy individuals (462) randomly selected from about 6000 men who had taken a 2-day health examination were studied. Out of the 30 physiological variables examined in routine check-ups, 11 variables were selected as suitable for the assessment of biological age based on the results of factor analysis and the physiological meaning of each test. This variable set was then submitted to principal component analysis, and the 1st principal component obtained from this analysis was used as an equation for assessing one's biological age. However, the biological age calculated from this equation is expressed as a score, so the estimated score was transformed to years (biological age) using the T-score idea. The biological age estimated by this method is practically useful and theoretically valid in contrast with the multiple regression model, because this approach eliminates and overcomes the following 2 big problems of the multiple regression model: (1) the distortion of the individual biological age at the regression edges; and (2) a theoretical contradiction in that a perfect model will merely be predicting the subject's chronological age, not his biological age.
OBJECTIVE: To estimate the prevalence of smoking among Saudi rural secondary school students and to explore their attitudes towards smoking. DESIGN: A cross-sectional study was conducted during May and June 1993, using a modified and translated version of the World Health Organization (WHO) standard questionnaire for the survey of smoking. Six rural male secondary schools near Riyadh were randomly selected, and 358 students representing half of the classes were included. RESULTS: Current smokers represented 17% of the students. The most common reasons for smoking were desire (32%), idleness (28%), imitation (22%) and enjoyment (20%). The majority knew about and understood the hazards of smoking. Around half of the smokers had started the habit before the age of 15. The media were the primary source of knowledge about smoking hazards for 66% of students; doctors (45%) and educators (30%) had a less significant role. Religion was the most important reason for not smoking among non-smokers. Financial reasons were less important (11%), probably reflecting the relatively cheap price of cigarettes. CONCLUSION: The size of the smoking problem is big enough to be considered a warning of an impending epidemic. Schools should have a greater role in health education. The government should adopt a policy of regular increases in cigarette taxes to cover part of the cost of treating smoking-related diseases.
We have identified a beta-thalassemia gene that carries a novel nonsense mutation in a Chinese patient. This mutation, a G to T substitution at the first position of codon 43, changes the glutamic acid coding triplet (GAG) to a terminator codon (TAG). Based on oligonucleotide hybridization studies of 78 Chinese and Southeast Asian beta-thalassemia chromosomes, we estimate that this mutation accounts for a small minority of the beta-thalassemia mutations in that population. Study of the expression of this cloned gene in a transient expression system demonstrated a 65% decrease in levels of normally spliced mutant beta-globin mRNA. However, the study of reticulocyte RNA isolated from an individual heterozygous for this mutation demonstrated a total absence of this mutant mRNA in vivo. The basis for this big discrepancy between the level of accumulated mRNA in vivo and in vitro is probably the result of differences in the stabilities of the mutant mRNA in erythroid cells.
Patch-clamp experiments on isolated nuclei revealed the existence of ionic channels on the nuclear envelope, but their exact localization and function are still unknown. Recent studies have demonstrated that ATP and calcium ions play an important role in nucleocytoplasmic protein traffic. ATP is essential to allow big molecules in and out of the nucleus. However, a cytoplasmic rise of calcium ions above 300 nm decreases both ATP-dependent transport and passive diffusion through the nuclear envelope. The use of isolated nuclei placed in a saline solution provides the possibility for testing only the compounds added in the bath or in the recording pipette. In the present study, we show that ATP is responsible for an increase of nuclear ionic permeability on isolated nuclei. This result not only confirms data previously reported in in situ nuclei, but also suggests that ATP is directly involved in the modulation of passive ionic permeability. In these particular experimental conditions, calcium ions decrease the channel current starting from a concentration of 1 microM. The parallelism in the modulation action of ATP and Ca++ between nuclear pores and ionic channels present on the nuclear envelope contributes to the support of the idea that an ionic pathway is associated with the pore complex.
High-throughput sequencing of human genomes and those of important model organisms (mouse, Drosophila melanogaster, Caenorhabditis elegans, fungi, archaea) and bacterial pathogens has laid the foundation for another "big science" initiative in biology. Together, X-ray crystallographers, nuclear magnetic resonance (NMR) spectroscopists, and computational biologists are pursuing high-throughput structural studies aimed at developing a comprehensive three-dimensional view of the protein structure universe. The new science of structural genomics promises more than 10,000 experimental protein structures and millions of calculated homology models of related proteins. The evolutionary underpinnings and technological challenges of automating target selection, protein expression and purification, sample preparation, NMR and X-ray data measurement/analysis, homology modeling, and structure/function annotation are discussed in detail. An informative case study from one of the structural genomics centers funded by the National Institutes of Health and the National Institute of General Medical Sciences (NIH/NIGMS) demonstrates how this experimental/computational pipeline will reveal important links between form and function in biology and provide new insights into evolution and human health and disease.
In order to determine whether various sensibility tests, not in common use at our hospital, are appropriate for the neurological screening of leprosy patients, an extended nerve function assessment (NFA) was done on 50 in- and outpatients who had been diagnosed as suffering from leprosy (100 hands and feet). The nerve function assessment battery consisted of Semmes-Weinstein monofilament testing (SWMT), moving 2-point discrimination (M2PD). Pinprick (PP), position sense (PS), vibration sense (VS) and voluntary muscle testing (VMT). In addition the SWMT was performed on 637 hands and 634 feet of field patients' in order to get a better indication of the prevalence of sensory impairment as measured with the SWMT. The SWMT has been shown to be a sensitive test of peripheral nerve function, therefore the other tests were compared with the SWMT. Results are reported separately for the ulnar, median and posterior tibial nerve. Test sites were the pulp of the distal phalanx of the index finger, the little finger and the big toe. Correlation between the SWMT and each of the other tests proved statistically significant; the closest correlations were between the SWMT, M2PD and PP for both ulnar and median nerves (r > 0.7, F test > 100, p < 0.0001). It is argued that the first tests to show nerve function impairment (NFI) are the M2PD and the SWMT. VS and PS were also absent in a significant proportion of patients. Arguments are presented that this may indicate advanced NFI. Results are compared with other data currently available in the literature.