Miracle-dz/UniFAR-FTUs huggingface dataset:
β-Arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors

It is becoming increasingly clear that signaling via G protein-coupled receptors is a diverse phenomenon involving receptor interaction with a variety of signaling partners. Despite this diversity, receptor ligands are commonly classified only according to their ability to modify G protein-dependent signaling. Here we show that β2AR ligands like ICI118551 and propranolol, which are inverse agonists for Gs-stimulated adenylyl cyclase, induce partial agonist responses for the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK) 1/2 thus behaving as dual efficacy ligands. ERK1/2 activation by dual efficacy ligands was not affected by ADP-ribosylation of Gαi and could be observed in S49-cyc– cells lacking Gαs indicating that, unlike the conventional agonist isoproterenol, these drugs induce ERK1/2 activation in a Gs/i-independent manner. In contrast, this activation was inhibited by a dominant negative mutant of β-arrestin and was abolished in mouse embryonic fibroblasts lacking β-arrestin 1 and 2. The role of β-arrestin was further confirmed by showing that transfection of β-arrestin 2 in these knockout cells restored ICI118551 promoted ERK1/2 activation. ICI118551 and propranolol also promoted β-arrestin recruitment to the receptor. Taken together, these observations suggest that β-arrestin recruitment is not an exclusive property of agonists, and that ligands classically classified as inverse agonists rely exclusively on β-arrestin for their positive signaling activity. This phenomenon is not unique to β2-adrenergic ligands because SR121463B, an inverse agonist on the V2 vasopressin receptor-stimulated adenylyl cyclase, recruited β-arrestin and stimulated ERK1/2. These results point to a multistate model of receptor activation in which ligand-specific conformations are capable of differentially activating distinct signaling partners.
Socioeconomic and demographic disparities in symptoms of orofacial pain.

OBJECTIVES The purpose of this study was to document the association between socioeconomic status (SES) and the prevalence and impact of orofacial pain by anatomical location. In addition, differential effects of SES on orofacial pain across levels of sex, race, and age were documented. METHODS The subjects were 724 participants in the Florida Dental Care Study, a study of oral health among dentate adults, aged 45 years and older at baseline. Pain prevalence and subjective ratings were assessed for a range of orofacial pain sites using a standardized telephone interview. RESULTS Lower SES was associated with reporting pain and pain impact at many, but not all, of the orofacial sites. Some sex, race, and age cohort differences in orofacial pain were found when adjusting for differences in socioeconomic position. The most consistent result, as evidenced by similar findings across orofacial pain sites, was that the effects of SES on orofacial pain appear to have a sex-differentiated effect. CONCLUSION Consistent with findings for other subjective measures of oral health, persons of lower SES are at increased risk for orofacial pain and pain-related behavioral impact.
Privacy concern toward using social networking services: A conceptual model

The success of social networking services (SNS) largely depends on the targeted users' adoption and usage behavior. However, privacy concern is one of the important barriers to SNS services application. A better understanding of online privacy concern and its general effect on users' intention toward using social networking services is an important research issue. This paper initiates discussion of this issue by proposing a conceptual model which places privacy concern as the focal point for SNS acceptance.
Survey finds physicians very wary of doctor ratings.

Of those who participated in the poll, 31 percent said they worked for health systems, while 24 percent worked at hospitals and 20 percent at group practices. Other answers included private practice (12 percent), academic health centers (9 percent) and managed care/insurance (1 percent). The largest number of respondents said their primary job title was medical director (147), followed by chief medical officer (115). Other titles included staff physician (103), department chair (47), vice president of medical affairs (27) and CEO (22). Although most of the respondents (69 percent) acknowledged they had checked their profiles on an online consumer website that rates physicians, a majority said they believed use of these sites among patients is low. About 55 percent believed 25 percent or fewer patients have used an online physician rating site, and an additional 35 percent put the number between 25 and 50 percent. Only 1 percent of respondents believed more than 75 percent of patients had used the sites. Among the physician leaders who said they had checked their online profile, most consulted Healthgrades.com (89 percent). Also popular were Vitals.com (33 percent) and Angie’s List (19 percent). Other sites listed by respondents were Yelp.com (13 percent), Doctorscorecard.com (9 percent), Ratemds.com (9 percent) and Mdnationwide.org (1 percent). Of the physicians who checked their online profiles, 39 percent said they agreed with their rating, and 42 percent said they partially agreed. Nineteen percent of the respondents said they didn’t agree. Of the physician leaders who said they hadn’t checked their online profile, 28 percent said their reason was because they were too busy. Another 21 percent said they didn’t think patients used them. The majority —51 percent—listed “other” and filled in their own reasons. Among them: In this article.
10 Neuropsychoanalytic notes on addiction

In other words, during development masturbation is normally replaced by adult sexual satisfaction, but where it is not it may be substituted by (another) addiction. These are quintessentially Freudian claims, museum-quality examples of the type. For that reason, perhaps, they are all too easily dismissed by addiction researchers today. If readers are willing to suspend judgment for a moment, though, and permit us to unpack the meaning of these claims and reconsider them in the light of contemporary neuroscience, their patience will be amply repaid. For all of his failings, Freud had an uncanny ability to identify the essence of a psychological problem. The fundamental problem of addiction exposed by the parallel that Freud drew with masturbation is that substance abuse (like masturbation) is an affectively rewarding activity that serves no biological purpose. Substance abuse generates hedonically positive affects in the brain (or reduces negative ones; for full discussion of this ‘opponent process’ issue in addiction research, see Khantzian, 2003) but does not sustain reproductive fitness. In fact, it does the opposite. Addiction therefore cannot be an evolutionarily proper use of the brain mechanisms in question, but it is psychologically compelling nonetheless.
Tools for Searching, Annotation and Analysis of Speech, Music, Film and Video - A Survey

This article examines the actual and potential use of software tools in research in the arts and humanities focusing on audiovisual (AV) materials such as recorded speech, music, video and film. The quantity of such materials available to researchers is massive and rapidly expanding. Researchers need to locate the material of interest in the vast quantity available, and to organize and process the material once collected. Locating and organizing often depend on metadata and tags to describe the actual content, but standards for metadata for AV materials are not widely adopted. Content-based search is becoming possible for speech, but is still beyond the horizon for music, and even more distant for video. Copyright protection hampers research with AV materials, and Digital Rights Management (DRM) systems threaten to prevent research altogether. Once material has been located and accessed, much research proceeds by annotation, for which many tools exist. Many researchers make some kind of transcription of materials, and would value tools to automate this process. Such tools exist for speech, though with important limits to their accuracy and applicability. For music and video, researchers can make use of visualizations. A better understanding (in general terms) by researchers of the processes carried out by computer software and of the limitations of its results would lead to more effective use of Information and Communications Technology (ICT).
A L-band active cold noise source for radiometer calibration

For application in radiometer calibration, a L-band(1400–1430MHz) active cold noise source(ACNS) is designed. A hybrid circuit has been realized with a Pseudomorphic High Electron Mobility Transistor(pHEMT), lumped elements and microstrip transmission lines. At ambient temperature, the ACNS exhibits an excellent noise temperature of only 68.7 K, a return loss higher than 25 dB and a negative temperature sensitivity of −1.64 K/O in the 1400–1430 MHz frequency range.
Postoperative arterial oxygen saturation in the pediatric population during transportation.

Hypoxemia (Sao, 90%, Pao, 58 mm Hg) in the recovery room (RR) is well documented in both the pediatric (1) and adult (2) population. The possibility of hypoxia during transport from operating rom (OR) to RR was examined by Tyler et al. (3) in the adult population; they reported that 35% of their patients were hypoxic and 12% severely hypoxic (Sao, <85%, Pao, 50 mm Hg). They attributed this high incidence of hypoxemia to obseity, N 2 0 diffusion, and decrease in functional residual capacity (FRC) below closing capacity resulting in ventilationlperfusion imbalance. However, we know of only one other report studying the pediatric population for oxygen desaturation (Sao,) during transport from OR to RR (4). To study the pattern of Sao, in healthy pediatric patients during transport from OR to RR has been made simple by the availability of the noninvasive pulse oximeter (Nellcor). This tool is easy to use, gives continuous oxygen saturation readings and, above all, has good correlation with arterial samples (5). We used this simple, widely accepted device to monitor desaturation in the healthy pediatric population during transport from OR to RR.
Dopamine D2 receptor gene expression and binding sites in adrenal medulla and pheochromocytoma.

To determine whether dopamine D2 receptors are present in normal and neoplastic chromaffin tissues, 10 pheochromocytomas and 5 human adrenal glands were studied. Dopamine D2 receptor messenger ribonucleic acid corresponding to a single band of approximately 2.5 kilobases was detected in both pheochromocytoma and human adrenal gland by Northern blot analysis. D2 receptor messenger ribonucleic acid levels determined by dot blot analysis were 3.1-fold lower in human adrenal medullas than in pheochromocytomas (P < 0.001). Simultaneous Scatchard analysis of [3H]spiperone binding experiments demonstrated the presence of two different binding sites in membrane preparations from bovine adrenal medullas [R1: Kd = 0.14 nmol/L; binding capacity (Bmax) = 6.2 fmol/mg protein: R2: Kd = 16 nmol/L; Bmax = 223 fmol/mg protein]. Similarly, two binding sites were present in membrane preparations from pheochromocytomas (R1: Kd = 0.39 nmol/L; R2: Kd = 61 nmol/L]. Binding capacities were greatly variable among pheochromocytomas (R1: Bmax = 12.0-372.5 fmol/mg protein; R2: Bmax = 1,000-11,586 fmol/mg protein). The relative potencies of different compounds to displace [3H]spiperone were spiperone > domperidone > (+)-butaclamol > quinpirole > SCH 23390 in bovine adrenal medulla, and spiperone >> domperidone > quinpirole > (+)-butaclamol > SCH 23390 in pheochromocytoma. We conclude that dopamine D2 receptors are synthesized in human adrenal medulla and pheochromocytoma tissues.
Knowledge Discovery Based on Multidisciplinary Simulation Data

The overall performance of a complex product generally depends on a number of specifications distributed in multi-teams from different disciplines. Multidisciplinary simulation analysis has been used widely in multidisciplinary design process. However, the knowledge discovery keeps bottleneck yet in building knowledge base for multidisciplinary design. In this paper, firstly, a framework of knowledge discovery from multidisciplinary simulation data is proposed. Secondly, a fuzzy-rough algorithm is developed to deal with the simulation data by combining the fuzzy set theory and rough set theory. The proposed knowledge discovery process is applied respectively to obtain some useful, implicit production rules with efficient measure. Finally, the method is demonstrated by a metal forming simulation problem. The results prove that knowledge discovery from simulation data is feasible, and the proposed method can be applied in other disciplinary simulation
T‐tubule swelling in hypertonic solutions: a freeze substitution study.

Striated muscles from Rana pipiens have been exposed for variable periods of time to Ringer solutions made hypertonic by addition of either sucrose or sodium chloride. The muscles have been rapid‐frozen and then prepared for electron microscopy by either freeze‐substitution, freeze‐fracture or cryoultramicrotomy. The only compartment greatly affected by hypertonicity is the transverse tubular system, which is visibly swollen. None of the elements of the sarcoplasmic reticulum increase in size.
Nonspecific serum iron in thalassemia: Quantitation and chemical reactivity

We reported earlier an abnormal iron population in the serum of patients with transfusional hemosiderosis secondary to thalassemia. The iron is not bound to transferrin, ferritin, or hemoglobin and is referred to as nonspecific iron. This publication reports studies of the chemical reactivity and nature of the nonspecific iron and the development and validation of a method for its quantitative analysis. The quantitation depends on the mobilization of this iron from nonspecific macromolecular binding sites by ethylenediamine tetraacetic acid and subsequent separation from Fe3+‐transferrin‐CO⅔− and residual hemoglobin by ultrafiltration. Analyses of filtrate iron were carried out by atomic absorption and colorimetric methods. The accuracy of the test was established via an ultrafiltration titration of serum of known unsaturated iron‐binding capacity. The method proved to be accurate and highly reproducible. Sera containing artificial introduced nonspecific iron were prepared. The reactivity of artificial and thalassemic nonspecific iron was examined with regard to reduction and chelation, and chelation by apotransferrin. Artificial and thalassemic nonspecific iron were found to be virtually identical in reactivity and to exhibit multiphasic kinetics consistent with nonspecific binding to several serum protein sites. The reaction of apotransferrin with nonspecific iron was complete within one minute. The reduction‐chelation and apotransferrin reactivity studies offer independent analyses of nonspecific serum iron concentrations which compared closely with the chelation‐ultrafiltration technique.
Integrating or disintegrating effects of customised care: the role of professions beyond NPM.

PURPOSE This paper aims to describe the integrating and disintegrating effects of professional actions in customised care. DESIGN/METHODOLOGY/APPROACH Using a qualitative case study, the authors examine the work practices and cultures of three Swedish child and adolescent psychiatric care units (CAP) charged with providing customised care in collaboration with other organisations. The authors conducted 62 interviews, made 11 half-day observations, and shadowed employees for two days. FINDINGS The social embeddedness of action is crucial to understanding the professions' integrating/disintegrating activities. In the internal social context of CAP, the professions adapt to productivity-enhancing new public management (NPM) principles, resulting in integrating effects between the different professions and administrative management in the CAP units. However, CAP exercises professional dominance over the cooperating organisations. Thus, in the external social context, CAP's resistance to customised care principles exacerbates the disintegration problems among the different organisations. PRACTICAL IMPLICATIONS The study concludes that, contrary to findings in many other studies, neither the professional logic nor NPM/customised care reforms determine the actions of professionals. In this case, the institutionalisation of some NPM methods blocks the adoption of customised care practices. ORIGINALITY/VALUE Contrary to the widely accepted idea that resource restriction is a main source of conflict between management and the professions, the professions accept and adapt to resource restrictions, even at the expense of de-emphasising the practices of customised care. Thus, since professionals choose different operational strategies depending on the social context, the success of a normative reform measure may depend in part on its social context.
177Lu-DOTATATE Molecular Radiotherapy for Childhood Neuroblastoma

This study tested the principle that 68Ga-DOTATATE PET/CT may be used to select children with primary refractory or relapsed high-risk neuroblastoma for treatment with 177Lu-DOTATATE and evaluated whether this is a viable therapeutic option for those children. Methods: Between 2008 and 2010, 8 children with relapsed or refractory high-risk neuroblastoma were studied with 68Ga-DOTATATE PET/CT. The criterion of eligibility for 177Lu-DOTATATE therapy was uptake on the diagnostic scan equal to or higher than that of the liver. Results: Of the 8 children imaged, 6 had abnormally high uptake on the 68Ga-DOTATATE PET/CT scan and proceeded to treatment. Patients received 2 or 3 administrations of 177Lu-DOTATATE at a median interval of 9 wk and a median administered activity of 7.3 GBq. Of the 6 children treated, 5 had stable disease by the response evaluation criteria in solid tumors (RECIST). Of these 5 children, 2 had an initial metabolic response and reduction in the size of their lesions, and 1 patient had a persistent partial metabolic response and reduction in size of the lesions on CT, although the disease was stable by RECIST. One had progressive disease. Three children had grade 3 and 1 child had grade 4 thrombocytopenia. No significant renal toxicity has been seen. Conclusion: 68Ga-DOTATATE can be used to image children with neuroblastoma and identify those suitable for molecular radiotherapy with 177Lu-DOTATATE. We have shown, for what is to our knowledge the first time, that treatment with 177Lu-DOTATATE is safe and feasible in children with relapsed or primary refractory high-risk neuroblastoma. We plan to evaluate this approach formally in a phase I–II clinical trial.
Achtsamkeitsmeditation bei chronischen Erschöpfungs-, Überforderungs- und Schmerzsyndromen

Chronische Erschöpfung und Überforderung sind begünstigende Faktoren für chronische Schmerzsyndrome. Dies gilt auch umgekehrt. Ein Behandlungsziel in einem multimodalen Therapiekonzept sollte sein, dem Patienten Zugang zu Handlungsmöglichkeiten zu verschaffen, um Stresssituationen zu bewältigen. Die Achtsamkeitsmeditation hat sich dabei als erfolgreiche Methode erwiesen, die von den Patienten im Alltag eingesetzt werden kann, wie Sie im folgenden Beitrag lesen.
The cutaneous pathology of lupus erythematosus: a review

The presentation of lupus erythematosus (LE) ranges from a skin rash unaccompanied by extracutaneous stigmata to a rapidly progressive lethal multiorgan disease. The diagnosis and subclassification is traditionally based on the correlation of serological and clinical findings. The latter include a photoinduced skin rash, arthralgia, arthritis, fever, Raynaud’s phenomenon, anemia, leukopenia, serositis, nephritis and central nervous sysdtem disease. The conventional classification scheme includes systemic, subacute cutaneous and discoid LE. Recent advances in our understanding of the cutaneous histopathology which correlates with the traditional forms of LE, along with certain novel LE subtypes, are the focus of this review. In addition to the main subtypes of LE, we will discuss associated vasculopathic lesions and the contribution of immunofluorescence microscopy to the diagnosis of LE and related connective tissue disease syndromes. Consideration will be given to unusual variants of LE such as anti‐Ro/SSA‐positive systemic lupus erythematosus (SLE), bullous SLE, lymphomatoid LE, lupus erythematosus profundus, drug induced LE, linear cutaneous LE, chiblains LE and parvovirus B19‐associated LE.
Robust 2-bit dual-linearly-polarised unit-cell for reflectarray applications

A new configuration of 2-bit dual-linearly-polarised unit-cell is introduced in X-band. It consists of two orthogonal and symmetrical cross-type printed triangular dipoles loaded by p.i. n diodes. This cell exhibits good performance with insertion loss lower than 2 dB and an isolation level better than 26 dB between both orthogonal polarisations. The impact of the diode features (off state capacitance) upon the phase response degradation is also investigated numerically. An improved cell design is then proposed to reduce the influence of the dipole loaded by non-symmetrical capacitances. This unit-cell exhibits 1.8 equivalent bit with 1.5% bandwidth obtained in measurement and a simulated cross-polarisation below −20dB.
Interface between Vascular Dementia and Alzheimer Syndrome: Nosologic Redefinition

Abstract: Vascular dementia is redefined so as to include noninfarct vascular dementia: vascular dementia caused by underlying vascular factors other than cerebral infarction. Data are presented that bring into focus the interface between vascular dementia and Alzheimer syndrome, and the ambiguous transition between multifocality and diffuse or generalized disease. By cross‐cutting both stroke and nonstroke vascular groups, arteriosclerosis, abnormal blood pressure, abnormal electrocardiogram, and other vascular factors are implicated in the distal causality of both infarct and noninfarct vascular dementia.
Occupational therapy's role in preventing acute readmissions.

Marla R. Robinson, MSc, OTR/L, BCPR, is Assistant Director, Inpatient Therapy Services, University of ChicagoMedicine, Chicago. The Patient Protection and Affordable Care Act of 2010 (ACA; Pub. L. No. 111–148) is designed to change the way health care services are delivered and reimbursed in the United States. Health care reform efforts stemming from the ACA will result in critical changes for providers and consumers of care. The ACA provides opportunities to examine and act on critical points of weakness in the health care system. One of those points of weakness is the high rate of readmissions to acute care. In this article we discuss the issues around this problem and suggest ways occupational therapy could serve the systemic goal of preventing these occurrences.
Estructura económica de los mercados turísticos

Este libro se dirige a estudiantes universitarios del Grado de Turismo, en concreto para la asignatura de Estructura de Mercados, aunque sus contenidos son tambien de gran utilidad para los profesionales de los diferentes ambitos relacionados con la actividad turistica. Para su redaccion, se ha contado con un amplio grupo de expertos en Economia del Turismo, la mayor parte de ellos con docencia en esta asignatura en sus respectivas universidades, que proponen un analisis riguroso, claro y ameno de los principales componentes de la actividad turistica. Para facilitar su uso como libro de texto, ademas de realizarse una exposicion clara, ordenada y pedagogica de los temas tratados, en cada capitulo se incluye un resumen con las ideas mas importantes que debe retener el alumno, asi como un conjunto de actividades para realizar en clase, preguntas de repaso y una bateria de preguntas tipo test (con un solucionario al final del libro). Ademas, se incluye una propuesta de Actividad Academicamente Dirigida para cada uno de los capitulos.