Miracle-dz/UniFAR-FTUs huggingface dataset:
Opioid peptide receptor studies. 12. Buprenorphine is a potent and selective μ/κ antagonist in the [35S]‐GTP‐γ‐S functional binding assay

We utilized the [35S]‐GTP‐γ‐S functional binding assay to determine the selectivity of opioid receptor agonists in guinea pig caudate membranes. The study focused on two opioid agonists used for treating opioid‐dependent patients: methadone and buprenorphine. Selective antagonists were used to generate agonist‐selective conditions: TIPP + nor‐BNI to measure μ receptors, CTAP + nor‐BNI to measure γ receptors and TIPP + CTAP to measure κ receptors. The assay was first validated with opioid agonists of known subtype specificity (DAMGO for μ, SNC80 for δ, and U69,593 for κ receptors). Methadone‐stimulated [35S]‐GTP‐γ‐S binding was μ‐specific and less potent and efficacious than etorphine (Kd = 1,537 nM vs. Kd = 7.8 nM). Buprenorphine failed to stimulate [35S]‐GTP‐γ‐S binding but inhibited agonist‐stimulated [35S]‐GTP‐γ‐S binding. The antagonist‐Ki values (nM) of buprenorphine at μ, δ, and κ receptors were 0.088 nM, 1.15 nM, and 0.072 nM, respectively. The antagonist‐Ki values (nM) of naloxone at μ, δ, and κ receptors were 1.39 nM, 25.0 nM, and 11.4 nM, respectively. Autoradiographic studies showed that buprenorphine failed to stimulate [35S]‐GTP‐γ‐S binding in caudate‐level rat brain sections but blocked DAMGO‐stimulated [35S]‐GTP‐γ‐S binding. In cells expressing the cloned rat μ receptor, buprenorphine was a partial agonist and potent μ antagonist. Administration of buprenorphine to rats produced a long‐lasting (>24 h) decrease in μ and κ2 receptor binding and attenuated μ‐stimulated [35S]‐GTP‐γ‐S binding. Viewed collectively, these data indicate that, in this assay system, buprenorphine is a potent μ and γ receptor antagonist. The clinical implications remain to be elucidated. Synapse 34:83–94, 1999. Published 1999 Wiley‐Liss, Inc.
Sampling Strategies for Estimation of Parameters Related to Ground Water Quality

Multiple theoretical sampling designs are studied to determine whether sampling designs can be identified that will provide for characterization of ground water quality in rural regions of developing nations. Sampling design in this work includes assessing sampling frequency, analytical methods, length of sampling period, and requirements of sampling personnel. The results answer a set of questions regarding whether using innovative sampling designs can allow hydrogeologists to take advantage of a range of characterization technologies, sampling strategies, and available personnel to develop high‐value, water‐quality data sets. Monte Carlo studies are used to assess different sampling strategies in the estimation of three parameters related to a hypothetical chemical observed in a ground water well: mean concentration (MeanC), maximum concentration (MaxC), and total mass load (TML). Five different scenarios are simulated. These scenarios are then subsampled using multiple simulated sampling instruments, time periods (ranging from 1 to 10 years), and sampling frequencies (ranging from weekly to semiannually to parameter dependent). Results are analyzed via the statistics of the resulting estimates, including mean square error, bias, bias squared, and precision. Results suggest that developing a sampling strategy based on what may be considered lower quality instruments can represent a powerful field research approach for estimating select parameters when applied at high frequency. This result suggests the potential utility of using a combination of lower quality instrument and local populations to obtain high frequency data sets in regions where regular monitoring by technicians is not practical.
School Days

For most children in North America, September signals the start of the school year. In my village on the outskirts of Chicago, both parents commonly accompany their 5-yearolds to the first day of kindergarten. Although the faces of the children may occasionally betray a bit of apprehension, their primary emotions are intense joy and excitement at the prospect of beginning a new phase of adventure and independence. Any tears in evidence are more likely to adorn the cheeks of their parents, who know that their little ones are indeed taking a big step toward ultimate separation. These first-day-of-school attitudes will evolve over the ensuing years—the children feeling more dread than excitement over the demise of the carefree days of summer, the parents relieved to be divested of their offspring after several months of intense proximity. As the children morph into adolescents, these feelings usually become more pronounced. This is particularly true for the parents, who may be increasingly delighted to foist their hormone-wracked teenagers onto the salaried minions of the Board of Education. The emotions of that first day of kindergarten won’t return until the kids go off to college, the youth again excited at the beginning of young adulthood, the parents realizing with dismay that they really are getting rid of their aggravating yet somehow endearing progeny. The quotation at the top of this editorial has a personal meaning for me. As a child, I had to endure the embarrassment of my father frequently repeating it in reference to his 3 sons. In fact, I thought that he had originated the metaphor until I researched it in preparation for this piece. Then I learned that it is attributed to Cornelia, the secondcentury bc Roman mother of 12 children including the famous brothers Tiberius and Gaius Gracchus. It has endured because it epitomizes the importance of our youth, not just to their parents but to the future of humankind. I was reminded of the quotation by 2 current publications, an article in this month’s American Journal of Sports Medicine and a just-released consensus statement from the International Olympic Committee (IOC). The first piece, The Effects of Timing of Pediatric Knee Ligament Surgery on Short-term Academic Performance in School-Aged Athletes, by Trentacosta et al, reminds us of the importance of education in the lives of our younger patients. Whether youngsters look forward to it or not, school plays a central role in their preparation for adulthood. In this Editorial
Risk factors for coronary heart disease among immigrant women from Iran and Turkey, compared to women of Swedish ethnicity.

OBJECTIVES The aim of the study was to compare a group of immigrant women from the Middle East living in Sweden to Swedish-born controls regarding the prevalence of certain cardiovascular risk factors. DESIGN Health survey of randomly selected foreign-born women and women native in Sweden. SETTING Uppsala, Sweden. SUBJECTS A total of 107 immigrant women aged 35-64 years from the Middle East (Iran [N=71] and Turkey [N=36]) living in Uppsala and residents in Sweden for at least three years and a control group of ethnic Swedish women (N=50). MAIN OUTCOME MEASURES A questionnaire and a clinical examination specially directed towards measuring cardiovascular risk factors and prevalence of obesity, diabetes mellitus, and hypertension. RESULTS A less beneficial cardiovascular risk profile was found among immigrant women than among ethnic Swedish women. Turkish women had substantially higher body mass index (BMI), larger waist, higher waist/hip ratio and sagittal abdominal diameter, higher levels of serum triglycerides, and lower HDL cholesterol concentration compared with Swedish-born women. A similar tendency was seen also for Iranian women. CONCLUSION The present study shows important ethnic differences in cardiovascular disease risk factor pattern. Immigrant women from Iran and Turkey are heavier than women born in Sweden and have a higher prevalence of abdominal obesity, an unfavorable lipid profile, and a high degree of physical inactivity during leisure time, which may predispose for a higher incidence of diabetes and atherosclerotic cardiovascular disease.
ION MOVEMENTS DURING NERVE ACTIVITY

There are several different ways in which the electric activity of a nerve fiber depends on movements of inorganic ions. In the first place, activity at one point on a fiber stimulates the regions ahead by means of local-circuit currents flowing forward in the axis cylinder, out through the membrane, and back in the external fluid. The current in the external fluid is clearly carried by a straightforward process of conduction in an electrolyte, and the same thing is almost certainly true of the current in the axis cylinder. Evidence for this is given by the three following facts: (1) that the longitudinal current obeys Ohm’s law fairly closely (Hodgkin and Rushton, 1946; Rashbass and Rushton, 1949); (2) that the specific resistance of the axoplasm is about what would be expected for an aqueous solution of the ions that are known by chemical analysis to be present; and (3) that the mobility and diffusion coefficient of the internal K+ are close to those in aqueous solution (Hodgkin and Keynes, 1953). The ions in question are partly inorganic-notably potassium-but organic ions are also concerned in some cases a t least. Thus, there are considerable quantities of dicarboxylic amino acids in crustacean nerve (Silber, 1941 ; Lewis, 1952); these are also present in squid nerve, but here the predominant anion appears to be isethionate (Koechlin, 1955). Phosphate esters are also likely to carry an appreciable fraction of the current in all kinds of nerve. A second way in which ion movements are important is in the maintenance of the resting potential. As is well known, Bernstein (1902) suggested, on the basis of the dependence of the demarcation potential on temperature, that the resting potential is a concentration potential, due probably to potassium ions. The ability of K ions to cross the membrane that is required on this theory has been amply demonstrated in recent years both by observing net movements (Boyle and Conway, 1941) and by tracer measurement of K exchange in the resting state (Krogh, 1946, and Keynes and Lewis, 1951u, among others). Although these downhill movements of K are clearly an important factor, they are not the only means by which positive charge is carried outward to maintain the resting potential. On the one hand, C1 ions probably act in the same way (Boyle and Conway, 1941; Hodgkin and Katz, 1949~); Bernstein himself was aware that the C1 concentration ratio was in the right direction, but he appears to have thought (1912, page 99) that an emf due to chloride ions should add to that due to K+, while in fact it is the currents carried by the various ionic species that are additive, the p.d. across the membrane being the same for all. On the other hand, there are also “active” movements of ions (Na and K), which we may regard as the third kind of ion movement of importance in nerve activity. These active movements, in which the net flux of the ion is in the direction that requires work to be done against its electrochemical gradient, have been much studied by tracer methods, and they are clearly essential for the
Is psychotherapy for personality disorders worth it?

P sychiatrists' eyes may glaze upon encountering an article with " economic " in the title and containing jargon like " QALY " (quality-adjusted life-years) and " nonparametric bootstrap replication. " As a profession, psychiatrists are not terribly good with numbers and money (or we' d be in better economic shape). Yet the study by Bamelis and colleagues in this issue 1 deserves your rapt attention. As a non-economically focused psychiatrist, I recommend it to you. There is a dearth of good studies of the cost-effectiveness, cost-utility, and cost-offset of psychiatric treatments, particularly psychotherapies. The authors of this sophisticated Dutch multisite trial compared the costs of schema therapy, clarification-oriented therapy, and treatment as usual (which in the Netherlands tends to mean adequate treatment) in a large randomized trial of 320 patients meeting DSM-IV criteria for avoidant, dependent, obsessive-compulsive, paranoid, histrionic, or narcissistic personality disorders. Schema therapy, the most clinically effective treatment, also had the best economic outcomes across a broad range of health-related and other societal variables. It is interesting to study the costs of treating personality disorders, which by definition are chronically debilitating and for which psychotherapy is the keystone of treatment. Moreover, the 6 personality disorders studied have received relatively little treatment attention relative to borderline personality disorder. Historically, the first hurdle psychotherapy research had to leap was whether psychotherapy worked. 2 With several psychotherapies having now amply demonstrated efficacy and effectiveness for multiple diagnoses, including some personality disorders, the next hurdle for psychotherapy may be cost. In the United States, insurance companies have continued to reward psychiatrists for prescribing medications rather than sitting, listening, and talking with patients, which the insurers still seem to consider an endless process and a black hole for costs. Even though most patients with mood and anxiety disorders prefer psychotherapy to pharmacotherapy, 3 the ratio of treatments they are receiving has increasingly tilted toward pharmacotherapy, 4 no doubt in part because of wrong-headed insurance-related economic incentives. 5 Personality disorders are precisely the sort of diagnoses insurance companies have most feared: chronic conditions requiring potentially endless, costly psychotherapy. This study shows not only that patients with personality disorders improved but also that delivering effective treatment saved money. American psychiatrists and other mental health professionals interested in preserving (and prescribing) psychotherapies should thank our Dutch colleagues for this economic research supporting the use of talking therapy for personality disorders. This is a study to …
The PrsA lipoprotein is essential for protein secretion in Bacillus subtilis and sets a limit for high‐level secretion

Mutations of the prsA gene of Bacillus subtilis have indicated that the gene is involved in protein secretion and it encodes a novel component of the cellular secretion machinery. We now demonstrate that the gene product is a membrane‐associated lipoprotein, presumably bound to the outer face of the cytoplasmic membrane. Experiments to inactivate the prsA gene with insertions indicated that it is indispensable for viability. The cellular level of PrsA protein was shown to be decreased in prsA mutants with decreased level of exoproteins, consistent with an essential function in protein secretion. An increased amount of cellular PrsA protein was introduced by Increasing the copy number of prsA in B. subtilis. This enhanced, from six‐ to twofold, the secretion of α‐amylases and a protease in strains, which expressed high levels of these exoenzymes. This suggests that PrsA protein is the rate‐limiting component of the secretion machinery, a finding that is of considerable biotechnological interest.
Osteoprotegerin in pediatric Crohn's disease and the effects of exclusive enteral nutrition

Background: Osteoprotegerin (OPG) may have proinflammatory roles in addition to its contribution to the maintenance of bone mass. Exclusive enteral nutrition (EEN) is an established therapy for the induction of remission in Crohn's disease (CD). The aims of this study were to ascertain serum, fecal, and mucosal expression of OPG in children with CD and to investigate the effects of EEN on OPG expression. Methods: OPG was measured by enzyme‐linked immunosorbent assay in serum, mucosal, and fecal samples collected from children with CD and controls. Fecal and Serum OPG was measured prior to and following 6‐8 weeks of EEN therapy. Results: Children with CD (n = 82) and controls (n = 45) were included. Mucosal and fecal OPG levels were elevated in CD compared to controls (P = 0.018 and P < 0.0001, respectively). Serum OPG was elevated in children with severe CD (P = 0.005). Serum and fecal OPG levels dropped significantly following EEN therapy (P = 0.0001 and P = 0.002, respectively). Conclusions: Increased serum and fecal OPG are seen in active CD and likely originate from the inflamed gut. Fecal and serum OPG decrease following EEN therapy. Further investigation of OPG and related proteins in the setting of IBD is now required. (Inflamm Bowel Dis 2011;)
Managing health problems in people with intellectual disabilities

#### Summary points People with intellectual disabilities have a higher prevalence of health problems than the general public, and their health needs are often unrecognised and unmet.1 People with intellectual and other disabilities are also more likely to develop secondary health conditions.w1 Improving the health of people with disabilities during their lives is a specific aim of the Healthy People 2010 initiative in the United States,2 the Valuing People initiative in the United Kingdom,w2 and the Pomona project (www.pomonaproject.org),3 a public health initiative funded by the European Union to develop and test a set of health indicators for people with disabilities. A recent randomised controlled trial on annual health screening in people with intellectual disabilities found an improvement in health in the intervention group.4 Nevertheless, epidemiological research on the health of people with intellectual disabilities is limited. We present here an up-to-date overview for medical generalists. Epidemiological research shows a prevalence of intellectual disability of about 0.7% (a figure mostly derived from service registrations—funding bodies or service providers). 5 w3 In a recent conceptual review, Mont challenges the usefulness of a single summary indicator to capture disability,6 which is not a health condition borne by an individual. Rather, disability is, he says, “complex and multifaceted, with …
Origin of the hematopoietic system in the human embryo

The continuous generation of blood cells throughout life relies on the existence of hematopoietic stem cells (HSC) generated during embryogenesis. Given the importance of HSC transplantation in cell‐based therapeutic approaches, considerable efforts have been made toward understanding the developmental origins of embryonic HSC. Adult‐type HSC are first generated in the aorta‐gonad‐mesonephros (AGM) region between days 27 and 40 of human embryonic development, but an elusive blood‐forming potential is present earlier in the underlying splanchnopleura. It is relatively well accepted that the HSC emerge in the AGM through a hemogenic endothelium, but the direct precursor of this cell type remains to be clearly identified. This review is intended to summarize the recent advances made to understand the origins of hematopoietic stem cells in the early human embryo. In addition, we discuss in detail the discovery of the angiotensin‐converting enzyme (ACE) as a novel marker of human HSC and of prehematopoietic precursors inside the embryo.
Potential and Electric Field Distribution Analysis of Field Limiting Ring and Field Plate by Device Simulator

Potential and strength of surface electric field distribution have strongly influence on breakdown voltage and reliability of power semiconductor devices. Potential distribution can be determined by different field-limiting ring and field plate design which can be described by solving Poisson's equation in one dimension briefly. In this paper, the influence of design factors such as spacing between main junction and ring, ring width, and field plate width on potential and strength of surface electric field distribution are analyzed. From the simulation results, the relationship between those factors and potential and strength of surface electric field distribution can be found. Understanding the effect of design factors upon the junction termination edge, multi field-limiting rings and field plates of high breakdown power devices can be designed.
The seas of language

1. What is a Theory of Meaning? (I) 2. What is a Theory of Meaning? (II) 3. What do I Know When I Know a Language? 4. What does the Appeal to Use do for the Theory of Meaning? 5. Language and Truth 6. Truth and Meaning * 7. Language and Communication 8. The Source of the Concept of Truth 9. Mood, Force, and Convention * 10. Frege and Husserl on Reference 11. Realism 12. Existence 13. Does Quantification Involve Identity? 14. Could there be Unicorns? + 15. Causal Loops 16. Common Sense and Physics 17. Testimony and Memory * 18. What is Mathematics About? 19. Wittgenstein on Necessity: Some Reflections 20. Realism and Anti-Realism *
Anti‐neutrophil cytoplasm antibodies, anti‐GBM antibodies and anti‐dsDNA antibodies in glomerulonephritis

Abstract. The diagnostic potential of assays detecting anti‐neutrophil cytoplasm antibodies (ANCA), anti‐GBM antibodies and anti‐dsDNA antibodies was evaluated by examining sera from time of admission in a consecutive series of 455 patients with biopsy verified primary or secondary glomerulonephritis (GN). ANCA were classified into c‐ and p‐ANCA by indirect immunofluorescence (IIF) and ELISAs using alfa‐granule extract, proteinase‐3, myeloperoxidase (MPO), elastase and lactoferrin. C‐ANCA was virtually confined to 64 patients with systemic small vessel vasculitis, 66–74% being c‐ANCA positive. P‐ANCA against MPO, seen in 47 patients, segregated through many diagnostic categories of primary and secondary severe GN. ANCA against lactoferrin and elastase were rare. Anti‐dsDNA positive patients constituted 57% of the 44 ANA‐positive patients with systemic lupus erythematosus.
Predictors of early retirement and rehabilitation for use in a screening to detect workers in need of rehabilitation

In the German pension insurance sector a screening is being suggested to ensure the participation in rehabilitation measures of workers at risk of health-related early retirement. Screening presupposes empirical indicators of rehabilitation needs. A study is presented that determined predictors of early retirement and rehabilitation from longitudinal data for use in a screening for the selection of workers likely to be in need of rehabilitation. We gathered longitudinal data by conducting a second survey with a cohort for which the first survey had delivered clinical findings, lab. values, medical diagnoses and self reports regarding morbidity, medication, health-related behavior, family- and occupational-related strains, and sociodemographic information (first survey T0: 1975/76, n = 3.968; second survey T1: 1992/93, n = 28.463). The survey of T1 also comprised inquiries of the pension insurance institutions concerning the retirement and rehabilitation status for pension-insured study subjects (n = 1.794). Based on these subjects, using multi- and bivariate regression analysis, we determined those T0 variables which were significantly related to the events of early retirement (98 cases/357 controls), rehabilitation (127 cases/200 controls) and early retirement or rehabilitation (185 cases/270 controls) in the period T0-T1. The significant T0 variables were subsequently used for the definition of a selection index which measured rehabilitation need by a simple sum score (number of significant T0 variables present). We tested the discriminative power of this index for a subsample of the cohort (cases who retired early or underwent rehabilitation and controls). The index classified 68% of the cases correctly. The sensitivity reached 57% and the specificity 76%. In connection with this result, the long prognostic time interval (up to 17 years) has to be considered. In the case of screening the preselection of workers via the index would occur at the same time as the medical assessment of the actual need for rehabilitation. An earlier study showed that this would raise sensitivity and specificity of an index based on predictors of early retirement substantially.