Miracle-dz/UniFAR-FTUs huggingface dataset:
A Fluorescence Resonance Energy Transfer-based M2 Muscarinic Receptor Sensor Reveals Rapid Kinetics of Allosteric Modulation*

Allosteric modulators have been identified for several G protein-coupled receptors, most notably muscarinic receptors. To study their mechanism of action, we made use of a recently developed technique to generate fluorescence resonance energy transfer (FRET)-based sensors to monitor G protein-coupled receptor activation. Cyan fluorescent protein was fused to the C terminus of the M2 muscarinic receptor, and a specific binding sequence for the small fluorescent compound fluorescein arsenical hairpin binder, FlAsH, was inserted into the third intracellular loop; the latter site was labeled in intact cells by incubation with FlAsH. We then measured FRET between the donor cyan fluorescent protein and the acceptor FlAsH in intact cells and monitored its changes in real time. Agonists such as acetylcholine and carbachol induced rapid changes in FRET, indicative of agonist-induced conformational changes. Removal of the agonists or addition of an antagonist caused a reversal of this signal with rate constants between 400 and 1100 ms. The allosteric ligands gallamine and dimethyl-W84 caused no changes in FRET when given alone, but increased FRET when given in the presence of an agonist, compatible with an inactivation of the receptors. The kinetics of these effects were very rapid, with rate constants of 80–100 ms and ≈200 ms for saturating concentrations of gallamine and dimethyl-W84, respectively. Because these speeds are significantly faster than the responses to antagonists, these data indicate that gallamine and dimethyl-W84 are allosteric ligands and actively induce a conformation of the M2 receptor with a reduced affinity for its agonists.
Prevalence of leukotoxic genotypes of Actinobacillus actinomycetemcomitans in Brazilians with chronic periodontitis

Actinobacillus actinomycetemcomitans is considered a major etiologic agent of aggressive periodontitis but this species has also been associated with other forms of periodontal disease. Further, highly leukotoxic strains are related to severity of disease. This investigation determined the prevalence of A. actinomycetemcomitans and the occurrence of the leukotoxin gene 530-bp deletion in Brazilian subjects with chronic periodontitis. Twenty periodontally healthy and 20 chronic periodontitis subjects were selected. Full-mouth clinical examination was carried out at 6 sites/tooth. Subgingival biofilm samples were collected from the 3 deepest sites and 3 healthy sites from periodontitis subjects, as well as from 3 sites of individuals with periodontal health. A. actinomycetemcomitans and the genetic deletion were determined by the polymerase chain reaction. Significant differences were sought by Mann-Whitney, Chi-square, and Wilcoxon sign tests. Periodontitis subjects presented a higher prevalence (75%) of A. actinomycetemcomitans than individuals with health (45%) (p = 0.053). A mean frequency of 57.5% of A. actinomycetemcomitans - positive sites was observed in the periodontitis group. Of those, 75% were diseased, whereas 40% were healthy sites (p = 0.0001). Healthy subjects showed a mean frequency of 35% of positive sites. In contrast, the genetic deletion was detected only in 4 diseased sites from 2 chronic periodontitis patients. A high prevalence of A. actinomycetemcomitans was observed in Brazilians with chronic periodontitis. However, the leukotoxin gene 530-bp deletion was rarely detected in the subgingival biofilm of these subjects.
Endoscopic ultrasound-guided placement of AXIOS stent for drainage of pancreatic fluid collections

Pancreatic fluid collections (PFCs) have conventionally been treated with surgery, percutaneous drainage, or with the more recently established endoscopic ultrasound (EUS)-guided drainage modality. Currently, endoscopic plastic or metallic stents are used for PFC drainage. Plastic stents present issues with stent migration and premature occlusion requiring frequent stent exchanges or placement of additional stents. Metallic stents are tubular and may migrate, resulting in inefficient drainage, content leakage, retrieval and replacement, and possible mucosal injury. The aim of this review was to summarize and evaluate the clinical and technical effectiveness of EUS-guided placement of the recently developed AXIOS stent, a lumen-apposing self-expandable metallic stent (LASEMS)for PFC drainage. A literature review was performed to identify the studies describing this technique. In this review article we have summarized case series or reports describing EUS-guided LASEMS placement. The indications, techniques, limitations and complications reported are discussed. A total of 298 patients were included across all studies described thus far in the literature. Overall, a 97% technical success rate and a 96% clinical success rate have been reported. Early and late complications related to the placement or removal of LASEMS have been reported, however few cases have presented life-threatening results. EUS-guided PFC drainage and LASEMS placement can be a safe and effective alternative approach in the management of selected patients.
The blood vessels of the dento-gingival junction.

The arrangement of the blood vessels at the dento-gingival junction was studied in dogs, after perfusion with a carbon-gelalin mixture. In clinically healthy gingivae a plexus of blood vessels was observed close to the crevicular epithelium. This plexus extended under the entire surface of the crevicular epithelium, from the gingival margin to the base of the crevice. In chronically inflamed gingivae the layered arrangement of the blood vessels seen in healthy gingivae was replaced by a vascular bed with loop-like formations.
HOW CAN AUTHENTIC LEADERS CREATE ORGANIZATIONAL IDENTIFICATION ? AN EMPIRICAL STUDY ON TURKISH EMPLOYEES

This research presents the empirical results of a study exploring the relationships between the concepts of transactional and authentic leadership, trust in leader and organizational identification. The sample used in the analysis (N = 232) was taken in Turkish companies that abide by corporate governance rules. The results of the study indicate that transactional leadership has a positive relation with trust in leader and that this relationship is moderated by authentic leadership. Furthermore, trust in leader, as a full mediator, develops organizational identification among followers. The results also identify authentic transactional leadership behaviors that promote followers’ trust for their leaders and thus help to develop organizational identification. Implications and directions of future research are discussed at the end of the paper.
Acute endoscopic intervention in non-variceal upper gastrointestinal bleeding

Upper gastrointestinal bleeding is one of the commonest emergencies encountered by general physicians. Once haemodynamic stability has been achieved, therapeutic endoscopy is vital in control and arrest of bleeding. Various methods are available and the evidence is reviewed as to the most optimal approach. Clinical parameters including timing of endoscopy, risk stratification, and predictors of failure will also be discussed together with a summary of recommendations based on current available evidence.
Michelin Tire Syndrome: A Report of Two Siblings

Abstract: Michelin tire syndrome is a rare syndrome characterized by excessive folding of the skin. The diagnosis is mainly clinical. It has been found to be associated with noncutaneous anomalies, and probably reflects multiple underlying disorders. We report two siblings with Michelin tire syndrome, a 5‐year‐old boy and his sister both of whom had marked skin folds and facial anomalies. Histologic study found an increase in smooth muscle fibers of the dermis. Electron microscopy showed details of smooth muscle cells. We also review reported cases in the literature to contribute to a better understanding of this syndrome.
Probability models for estimating the probabilities of cascading outages in high-voltage transmission network

This paper discusses a number of probability models for multiple transmission line outages in power systems, including generalized Poisson model, negative binomial model, and exponentially accelerated model. These models are applied to the multiple transmission outage data for a 20-year period for North America. The probabilities of the propagation of transmission cascading outage are calculated. These probability magnitudes can serve as indexes for long-term planning and can also be used in short-term operational defense to such events. Results from our research show that all three models apparently explain the occurrence probability of higher order outages very well. However, the exponentially accelerated model fits the observed data and predicts the acceleration trends best. Strict chi-squared fitness tests were done to compare the fitness among these three models, and the test results are consistent with what we observe
Community Structure of a Mental Health Internet Support Group: Modularity in User Thread Participation

Background Little is known about the community structure of mental health Internet support groups, quantitatively. A greater understanding of the factors, which lead to user interaction, is needed to explain the design information of these services and future research concerning their utility. Objective A study was conducted to determine the characteristics of users associated with the subgroup community structure of an Internet support group for mental health issues. Methods A social network analysis of the Internet support group BlueBoard (blueboard.anu.edu.au) was performed to determine the modularity of the community using the Louvain method. Demographic characteristics age, gender, residential location, type of user (consumer, carer, or other), registration date, and posting frequency in subforums (depression, generalized anxiety, social anxiety, panic disorder, bipolar disorder, obsessive compulsive disorder, borderline personality disorder, eating disorders, carers, general (eg, “chit chat”), and suggestions box) of the BlueBoard users were assessed as potential predictors of the resulting subgroup structure. Results The analysis of modularity identified five main subgroups in the BlueBoard community. Registration date was found to be the largest contributor to the modularity outcome as observed by multinomial logistic regression. The addition of this variable to the final model containing all other factors improved its classification accuracy by 46.3%, that is, from 37.9% to 84.2%. Further investigation of this variable revealed that the most active and central users registered significantly earlier than the median registration time in each group. Conclusions The five subgroups resembled five generations of BlueBoard in distinct eras that transcended discussion about different mental health issues. This finding may be due to the activity of highly engaged and central users who communicate with many other users. Future research should seek to determine the generalizability of this finding and investigate the role that highly active and central users may play in the formation of this phenomenon.
Neurophysiological Alterations During Strategy-Based Verbal Learning in Traumatic Brain Injury

Background. Verbal learning and strategic processing deficits are common sequelae of traumatic brain injury (TBI); however, the neurophysiological mechanisms underlying such deficits remain poorly understood. Methods. We performed functional magnetic resonance imaging (fMRI) in 25 individuals with chronic TBI (>1 year after injury) and 20 matched healthy controls. Subjects were scanned while encoding word lists, with free recall and recognition assessed after each scanning run. To vary the strategic processing load, participants learned semantically unrelated words (Unrelated condition), semantically related words under null instruction conditions (Spontaneous condition), and semantically related words following training on the use of a semantic clustering strategy (Directed condition). Results. Behavioral performance on recall, recognition, and semantic clustering improved significantly as follows: Unrelated < Spontaneous < Directed. Individuals with TBI exhibited impaired yet parallel behavioral performance relative to control participants. The fMRI measures of brain activity during verbal encoding revealed decreased activity in participants with TBI relative to controls in left dorsolateral prefrontal cortex (DLPFC; BA 9) and in a region spanning the left angular and supramarginal gyri (BA 39/40). Functional connectivity analysis revealed evidence of a functional—but not anatomical—breakdown in the connectivity between the DLPFC and other regions specifically when participants with TBI were directed to use the semantic encoding strategy. Conclusion. After TBI, the DLPFC appears to be decoupled from other active brain regions specifically when strategic control is required. We hypothesize that approaches designed to help re-couple DLPFC under such conditions may aid TBI cognitive rehabilitation.
Pharmacological Chaperone-mediated in Vivo Folding and Stabilization of the P23H-opsin Mutant Associated with Autosomal Dominant Retinitis Pigmentosa*

Protein conformational disorders, which include certain types of retinitis pigmentosa, are a set of inherited human diseases in which mutant proteins are misfolded and often aggregated. Many opsin mutants associated with retinitis pigmentosa, the most common being P23H, are misfolded and retained within the cell. Here, we describe a pharmacological chaperone, 11-cis-7-ring retinal, that quantitatively induces the in vivo folding of P23H-opsin. The rescued protein forms pigment, acquires mature glycosylation, and is transported to the cell surface. Additionally, we determined the temperature stability of the rescued protein as well as the reactivity of the retinal-opsin Schiff base to hydroxylamine. Our study unveils novel properties of P23H-opsin and its interaction with the chromophore. These properties suggest that 11-cis-7-ring retinal may be a useful therapeutic agent for the rescue of P23H-opsin and the prevention of retinal degeneration.
Effect of a biopsychosocial approach on patient satisfaction and patterns of care

AbstractBACKGROUND: There is a growing tendency to include in medical curricula teaching programs that promote a biopsychosocial (BPS) approach to patient care. However, we know of no attempts to assess their effect on patterns of care and health care expenditures. OBJECTIVE: To determine whether 1) a teaching intervention aiming to promote a BPS approach to care affects the duration of the doctor-patient encounter, health expenditures, and patient satisfaction with care, and 2) the teaching method employed affects these outcomes. METHODS: We compared two teaching methods. The first one (didactic) consisted of reading assignments, lectures, and group discussions. The second (interactive) consisted of reading assignments, small group discussions, Balint groups, and role-playing exercises. We videotaped patient encounters 1 month before and 6 months after the teaching interventions, and recorded the duration of the videotaped encounters and whether the doctor had prescribed medications, ordered tests, and referred the patient to consultants. Patient satisfaction was measured by a structured questionnaire. RESULTS: Both teaching interventions were followed by a reduction in medications prescribed and by improved patient satisfaction. Compared to the didactic group, the interactive group prescribed even fewer medications, ordered fewer laboratory examinations, and elicited higher scores of patient satisfaction. The average duration of the encounters after the didactic and interactive teaching interventions was longer than that before by 36 and 42 seconds, respectively. CONCLUSIONS: A BPS teaching intervention may reduce health care expenditures and enhance patients’ satisfaction, without changing markedly the duration of the encounter. An interactive method of instruction was more effective in achieving these objectives than a didactic one.
Reversal of Diffusion Restriction After Embolization of Dural Arteriovenous Fistula: Case Report

BACKGROUND AND IMPORTANCE:We report a rare case of diffusion restriction caused by venous hypertension resulting from a dural arteriovenous fistula (DAVF) that completely reversed after successful embolization. CLINICAL PRESENTATION:A 54-year-old man presented with symptoms secondary to a DAVF. Magnetic resonance imaging (MRI) revealed left parieto-temporo-occipital diffusion restriction. The angiogram revealed a Cognard type III left lateral tentorial DAVF resulting in severe venous hypertension. Transarterial Onyx embolization was performed, resulting in angiographic cure of the fistula with normalization of the venous drainage in the left parieto-temporo-occipital region. A follow-up MRI examination performed 4 weeks after the embolization revealed resolution of the previously seen area of restricted diffusion. CONCLUSION:It is important to consider the possibility of diffusion restriction reversal, because misdiagnosis or the false assumption that irreversible cerebral infarction has occurred may inappropriately alter or delay the treatment of these aggressive lesions.
The genetics of Fuchs’ corneal dystrophy

Fuchs’ corneal dystrophy (FCD) is a common late-onset genetic disorder of the corneal endothelium. It causes loss of endothelial cell density and excrescences in the Descemet membrane, eventually progressing to corneal edema, necessitating corneal transplantation. The genetic basis of FCD is complex and heterogeneous, demonstrating variable expressivity and incomplete penetrance. To date, three causal genes, ZEB1, SLC4A11 and LOXHD1, have been identified, representing a small proportion of the total genetic load of FCD. An additional four loci have been localized, including a region on chromosome 18 that is potentially responsible for a large proportion of all FCD cases. The elucidation of the causal genes underlying these loci will begin to clarify the pathogenesis of FCD and pave the way for the emergence of nonsurgical treatments.
Design support for Wireless Sensor Networks based on the IEEE 802.15.4 standard

Within this paper a modeling environment for wireless sensor networks (WSN) is proposed. This environment consists of a framework, which represents the behavior of wireless sensor networks (WSN) in general and a library containing simulation models for the used hardware components (e.g. CPU and Transceiver) and software stacks. This library can be easily extended by new component models, node hardware configurations or embedded software. The developed environment allows the simulation of WSNs on a detailed level including all important parameters like RAM usage, power consumption and processor utilization. Therefore, the outcome of the simulation results can, among others, be used for software optimizations and for design of a suitable power supply. Even though the simulation environment allows this level of detail, it is not limited to this. E.g. at the starting point of the development, the user can implement more abstract models, which do not use all the features offered by the framework. Instead, during this phase of the development one could focus on the functional behavior of the implemented algorithms (e.g. routing) or the application itself. These models created in this early phase of the development can be refined throughout the development process. At this more detailed level of abstraction the software design can be verified very efficiently. Finally, this software can be transferred to an embedded target.
Free and bound propofol concentrations in human cerebrospinal fluid.

AIMS The aim of this study was to define the relationship between unbound propofol concentrations in plasma and total drug concentrations in human cerebrospinal fluid (CSF), and to determine whether propofol exists in the CSF in bound form. METHODS Forty-three patients (divided into three groups) scheduled for elective intracranial procedures and anaesthetized by propofol target control infusion (TCI) were studied. Blood and CSF samples (taken from the radial artery, and the intraventricular drainage, respectively) from group I (17 patients) were used to investigate the relationship between unbound propofol concentration in plasma and total concentration of the drug in CSF. CSF samples taken from group II (18 patients) were used to confirm the presence of the bound form of propofol in this fluid. The CSF and blood samples taken from group III (eight patients) were used to monitor the course of free and bound CSF propofol concentrations during anaesthesia. RESULTS For group I patients the mean (and 95% confidence interval) total plasma propofol concentration was 6113 (4971, 7255) ng ml(-1), the mean free propofol concentration in plasma was 63 (42, 84) ng ml(-1), and the mean total propofol concentration in CSF was 96 (76, 116) ng ml(-1) (P < 0.05 for the difference between the last two values). For group II patients the fraction of free propofol in CSF was 31 (26, 37)%. For group III patients the fraction of free propofol in CSF during TCI was almost constant (about 36%). CONCLUSIONS The unbound propofol concentration in plasma was not equal to its total concentration in CSF and cannot be directly related to the drug concentration in the brain. Binding of propofol to components of the CSF may be an additional mechanism regulating the transport of the drug from blood into CSF.
Triggered Earthquakes and the 1811-1812 New Madrid, Central United States, Earthquake Sequence

The 1811–1812 New Madrid, central United States, earthquake sequence included at least three events with magnitudes estimated at well above M 7.0. I discuss evidence that the sequence also produced at least three substantial triggered events well outside the New Madrid Seismic Zone, most likely in the vicinity of Cincinnati, Ohio. The largest of these events is estimated to have a magnitude in the low to mid M 5 range. Events of this size are large enough to cause damage, especially in regions with low levels of preparedness. Remotely triggered earthquakes have been observed in tectonically active regions in recent years, but not previously in stable continental regions. The results of this study suggest, however, that potentially damaging triggered earthquakes may be common following large mainshocks in stable continental regions. Thus, in areas of low seismic activity such as central/eastern North America, the hazard associated with localized source zones might be more far reaching than previously recognized. The results also provide additional evidence that intraplate crust is critically stressed, such that small stress changes are especially effective at triggering earthquakes.