Miracle-dz/UniFAR-FTUs huggingface dataset:
The FDA's role in medical device clinical studies of human subjects

This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices.
Minute Time Scale Prolyl Isomerization Governs Antibody Recognition of an Intrinsically Disordered Immunodominant Epitope*

Background: Kinetic discrimination is essential in antibody·antigen recognition. Results: An otherwise fast second-order reaction is limited by a slow proline isomerization of the epitope. Conclusion: The antibody recognizes the less populated isoform, suggesting presentation of the epitope as a non-native conformer. Significance: The conformational diversity of an intrinsically disordered viral epitope slows down the reaction with the antibody without specificity cost. Conformational rearrangements in antibody·antigen recognition are essential events where kinetic discrimination of isomers expands the universe of combinations. We investigated the interaction mechanism of a monoclonal antibody, M1, raised against E7 from human papillomavirus, a prototypic viral oncoprotein and a model intrinsically disordered protein. The mapped 12-amino acid immunodominant epitope lies within a “hinge” region between the N-terminal intrinsically disordered and the C-terminal globular domains. Kinetic experiments show that despite being within an intrinsically disordered region, the hinge E7 epitope has at least two populations separated by a high energy barrier. Nuclear magnetic resonance traced the origin of this barrier to a very slow (t½ ∼4 min) trans-cis prolyl isomerization event involving changes in secondary structure. The less populated (10%) cis isomer is the binding-competent species, thus requiring the 90% of molecules in the trans configuration to isomerize before binding. The association rate for the cis isomer approaches 6 × 107 m−1 s−1, a ceiling for antigen-antibody interactions. Mutagenesis experiments showed that Pro-41 in E7Ep was required for both binding and isomerization. After a slow postbinding unimolecular rearrangement, a consolidated complex with KD = 1.2 × 10−7 m is reached. Our results suggest that presentation of this viral epitope by the antigen-presenting cells would have to be “locked” in the cis conformation, in opposition to the most populated trans isomer, in order to select the specific antibody clone that goes through affinity and kinetic maturation.
Morphology, behavior, and histogenesis of the pelagosphera larva of Phascolosoma agassizii (Sipuncula)

Rice, Mary E. Morphology, Behavior, and Histogenesis of the Pelagosphera Larva of Phascolosoma agassizii (Sipuncula). Smithsonian Contributions to Zoology, number 132, 51 pages, 14 plates, 1973. —Morphology, behavior, and histology are described for the pelagosphera larva of Phascolosoma agassizii Keferstein. Observations are reported on histology, origin, and development of the following larval structures: body wall, coelom and coelomic elements, retractor muscles, digestive tract, buccal organ, lip gland, nervous system, nephridia, larval glands and terminal organ. Functional significance of certain structures, particularly organs associated with the mouth, is considered. Moreover, available information on developmental histology of other sipunculans is reviewed and intraas well as inter-phyletic comparisons are discussed. An account is given of the general morphology of the larva and a few observations are noted on larval locomotion and feeding behavior in the laboratory. Official publication date is handstamped in a limited number of initial copies and is recorded in the Institution's annual report, Smithsonian Year. SERIES COVER DESIGN: The coral Montastrea cavernosa (Linnaeus) . Library of Congress Cataloging in Publication Data Rice, Mary E. Morphology, behavior, and histogenesis of the pelagosphera larva of Phascolosoma agassizii (Sipuncula). (Smithsonian contributions to zoology, no. 132). Bibliography: p. 1. Phascolosoma agassizii. 2. Larvae—Worms. I. Title. II. Series: Smithsonian Institution. Smithsonian contributions to zoology, no. 132. QL1.S54 no. 132 [QL391.G5] 591'. O8s [595M7] 72-8959 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, D.C., 20402 Price $1.25 (paper cover)
Trends in methadone-related deaths in

Methadone has a long and successful history in the treatment of opioid-addiction. In recent years it h as become popular again as potent and inexpensive an algesic in patients with chronic pain. Since methadone has been used fatalities have been report ed. In our study all methadone-associated deaths in Zurich from 1998 to 2007 were analysed. Most of the 146 detected deaths of the past ten years occurred during substitution programmes or illicit ntake of methadone while only three of them could be attributed to methadone used as an analgesic. No ticeable in our study was the high percentage of cases of combined drug intoxication (76%). The most frequent co-intoxicants were alcohol and cocaine. Mortalities attributed to methadone intoxi cation alone were a rare finding and could only be detected in five cases of deceased who had received methadone maintenance treatment. The aim of our study is to assess the trends in the umber and nature of methadone-related fatalities in Zurich during the last nineteen years. For this pur pose a previous study from Zurich (1989-1997) was included, whereby a very long oberservation period an large number of cases resulted.
Evaluation of Single Field Uniform Dose (SFUD) Proton Pencil Beam Scanning (PBS) Planning Strategy for Lung Mobile Tumor Using a Digital Phantom

Purpose: To quantitatively evaluate four different Proton SFUD PBS initial planning strategies for lung mobile tumor. Methods and Materials: A virtual lung patient’s four-dimensional computed tomography (4DCT) was generated in this study. To avoid the uncertainties from target delineation and imaging artifacts, a sphere with diameter of 3 cm representing a rigid mobile target (GTV) was inserted into the right side of the lung. The target motion is set in superior-inferior (SI) direction from ? 5 mm to 5 mm. Four SFUD planning strategies were used based on: 1) Maximum-In-tensity-Projection Image (MIP-CT); 2) CT_average with ITV overridden to muscle density (CTavg_muscle); 3) CT_average with ITV overridden to tumor density (CTavg_tumor); 4) CT_average without any override density (CTavg_only). Dose distributions were recalculated on each individual phase and accumulated together to assess the “actual” treatment. To estimate the impact of proton range uncertainties, +/? 3.5% CT calibration curve was applied to the 4DCT phase images. Results: Comparing initial plan to the dose accumulation: MIP-CT based GTV D98 degraded 2.42 Gy (60.10 Gy vs 57.68 Gy). Heart D1 increased 6.19 Gy (1.88 Gy vs 8.07 Gy); CTavg_tumor based GTV D98 degraded 0.34 Gy (60.07 Gy vs 59.73 Gy). Heart D1 increased 2.24 Gy (3.74 Gy vs 5.98 Gy); CTavg_muscle based initial GTV D98 degraded 0.31 Gy (60.4 Gy vs 60.19 Gy). Heart D1 increased 3.44 Gy (4.38 Gy vs 7.82 Gy); CTavg_only based Initial GTV D98 degraded 6.63 Gy (60.11 Gy vs 53.48 Gy). Heart D1 increased 0.30 Gy (2.69 Gy vs 2.96 Gy); in the presence of ±3.5% range uncertainties, CTavg_tumor based plan’s accumulated GTV D98 degraded to 57.99 Gy (+3.5%) 59.38 Gy (? 3.5%), and CTavg_muscle based plan’s accumulated GTV D98 degraded to 59.37 Gy (+3.5%) 59.37 Gy (? 3.5%). Conclusion: This study shows that CTavg_Tumor and CTavg_Muscle based planning strategies provide the most robust GTV coverage. However, clinicians need to be aware that the actual dose to OARs at distal end of target may increase. The study also indicates that the current SFUD PBS planning strategy might not be sufficient to compensate the CT calibration uncertainty.
Cardiovascular Effects of Serotonin

The major target for circulating serotonin (released from aggregating platelets) appears to be the blood vessel wall (although little evidence is available), suggesting a role for the monoamine in controlling cardiac function. In cerebral blood vessels, serotonergic neurons are present, implying a potential serotonergic neurogenic control. Serotonin causes contraction of most large arteries and veins; it also causes contraction of venules. This is due mainly to direct activation of vascular smooth muscle, although amplification of the response to other endogenous vasoconstrictors (e.g., angiotensin II and norepinephrine) as well as facilitated release of norepinephrine may contribute. In peripheral blood vessels, the receptors mediating the contractions evoked by serotonin belong mainly to the 5-HT2-serotonergic subtype; in the coronary and cerebral arteries, this need not be the case. Vasodilator responses to serotonin are seen mainly at the arteriolar level, but they can also be observed in larger blood vessels. They can be caused by the release of other endogenous vasodilators (e.g., vasoactive intestinal polypeptide), direct relaxation of vascular smooth muscle, inhibition of adrenergic neurotrans-mission, or production of endothelium-derived relaxing factors). The dilator responses to serotonin are mediated by receptors with characteristics similar to 5-HT1-serotonergic binding sites. Aggregating platelets release enough serotonin to evoke both constrictor and dilator responses. The absence of endothelium may change the primary response to aggregating platelets from relaxation to contraction. The responsiveness of the blood vessel wall to serotonin can be augmented acutely by local hypoxia or by cooling. It is exaggerated in blood vessels taken from hypertensive or atherosclerotic animals. In hypertensive blood vessels, vasoconstrictor responses to serotonin may be augmented by the release of endothelium-derived contracting factors). Vasoconstrictor responses to serotonin may play a role in the etiology of vasospasm or in the maintenance of the augmented peripheral resistance in certain cases of arterial hypertension.
SURVEY PAPER FOR DIFFERENT SPARQL QUERY OPTIMIZATION TECHNIQUES

Motivated by the ongoing success of semantic web and the increasing amount of Linked Data available on the Web, new challenges to SPARQL query optimization are emerging. According to the static vs. dynamic and top down vs. bottom up type of query optimization, the paper describes survey of different approaches for query optimization like query rewriting, query analysis, selectivity of triple patterns, mixed strategy, and evaluating graph traversal algorithms for query optimization. It also discusses each optimization technique, their characteristics, the comparisons and several challenging problems in detail.
Imaging pulmonary emboli and deep venous thrombi with 99mTc-bitistatin, a platelet-binding polypeptide from viper venom.

UNLABELLED An imaging test that could locate both pulmonary emboli (PE) and their source, active deep venous thrombi (DVT), would be valuable in patient management. Bitistatin, an 83-amino-acid polypeptide isolated from Bitis arietans venom, binds avidly to the glycoprotein IIb/IIIa receptor on platelets. The goal of this study was to label bitistatin with 99mTc and assess its potential for imaging thrombi and emboli in vivo. METHODS Molecular modeling of bitistatin indicated that its primary amines are located on the opposite side of the molecule from the receptor-binding domain. The primary amines were reacted with succinimidyl-4-hydrazino nicotinate hydrochloride to place 2.4 hydrazino nicotinate (Hn) chelating groups per peptide molecule. Hn-bitistatin was labeled by incubation with 99mTc-glucoheptonate to 96 TBq/mmol and then tested for binding to platelets in vitro and for imaging of 24-h-old DVT and PE in a canine model used previously for other thrombus tracers. RESULTS 99mTc-Hn-bitistatin bound to stimulated platelets with a dissociation constant (Kd) = 32 nmol/L, similar to that of 125I-bitistatin (Kd = 41 nmol/L). In vivo, focal uptake was observed in planar images as early as 30 min (DVT) and 60 min (PE) after injection. Lesion uptake of 99mTc-Hn-bitistatin at 4 h after injection was calculated in terms of percentage injected dose per gram (%ID/g) of tissue and averaged 0.89 %ID/g PE and 0.79 %ID/g DVT. Lesion-to-background ratios averaged 34:1 (PE-to-lung), 18:1 (DVT-to-blood), and 284:1 (DVT-to-muscle). These values were not significantly different from iodinated bitistatin, but uptakes were higher than other tracers tested in the same model. CONCLUSION 99mTc-Hn-bitistatin retains the functional activity of the iodinated peptide, has higher DVT and PE uptakes than other thrombus tracers in this standardized model, and has target-to-background characteristics suitable for imaging both PE and DVT in a single test.
A slotted post-wall waveguide array with inter-digital structure for 45-deg linear and dual polarization

We propose a slotted post-wall waveguide array with an inter-digital structure for a 45/spl deg/ dual linear polarization antenna. Two arrays inter-digitally share the common aperture. The whole structure is fabricated perfectly in a single layer using post-wall waveguides. The unique difficulty for this array is that the adjacent waveguides for the same polarization are sparsely spaced by two times of the broadwall width. So, dielectric filling in the waveguide is indispensable for reducing the physical width of the waveguide and the resulting grating lobes. Another specific feature is that the two arrays are excited by traveling waves propagating in opposite directions. Five types of two-dimensional arrays were fabricated. The measurement results are reported.
The Relative Roles of Sulfate Aerosols and Greenhouse Gases in Climate Forcing

Calculations of the effects of both natural and anthropogenic tropospheric sulfate aerosols indicate that the aerosol climate forcing is sufficiently large in a number of regions of the Northern Hemisphere to reduce significantly the positive forcing from increased greenhouse gases. Summer sulfate aerosol forcing in the Northern Hemisphere completely offsets the greenhouse forcing over the eastern United States and central Europe. Anthropogenic sulfate aerosols contribute a globally averaged annual forcing of –0.3 watt per square meter as compared with +2.1 watts per square meter for greenhouse gases. Sources of the difference in magnitude with the previous estimate of Charlson et al. are discussed.
Gold nanorod probes for the detection of multiple pathogens.

Foodborne diseases are associated with ﬁve majorpathogens,includingE.coliO157:H7(E.coli)andSalmonellaTyphimurium(S.Typhimurium),andthecostsassociatedwithpreventive and curative measures to combat these ﬁve majorpathogens is estimated to be at least $6.9 billion annually,according tothe Economic ResearchService(ERS) in2000.
Financial Inclusion, Governance and Institution: Evidence from Developing Economies

This paper argues that strong economic governance and institution are important elements in improving financial inclusion especially for the poor segment of the society because markets, economic activity and transactions more generally, cannot function well in its absence. This paper utilizes the data of more than 100,000 individuals’ characteristics in the Global Findex database to examine how these different characteristics are associated with financial inclusion. This paper employs probit model to explain measures of financial inclusion and then augmented the model with governance and institutional variables using principal component analysis. The results suggest that neither the impacts of governance indicators nor the freedom indexes are conclusive, while economic freedom show mixed results on financial inclusion. Governance has positive influenced on people wanting to open an account and make saving in formal financial institutions, but negatively impacted on borrowing behaviour. There is also significant differences across countries in particular between Muslim countries and non-Muslim countries in explaining financial inclusion. The study suggests that removing corruption, increasing transparent legal framework, fair judicial proceedings and administration are essential for development and raising financial inclusiveness prospects.
Selective suppression of granuloma formation and delayed hypersensitivity in rabbits

The relationship between dermal delayed hypersensitivity (DH) and granulomatous hypersensitivity was studied in rabbits sensitized with killed mycobacteria. Specific antigen challenge of sensitized animals resulted in extensive pulmonary granulomatous inflammation and induced suppression of both dermal DH and dermal granuloma formation. Whereas suppression of DH was concomitant with pulmonary granuloma formation, as is the case in a number of granulomatous diseases, a causal relationship between the two did not exist. Both DH and dermal granulomatous hypersensitivity were significantly suppressed whether or not the antigen challenge was of a granulomagenic (particulate) or nongranulomagenic (soluble) form. The data presented indicate that granulomatous hypersensitivity and DH are selectively suppressed with regard to different anatomical sites.
Reduced Order Modeling for Feedback Control of a Flexible Wing at Low Reynolds Numbers

A variety of unsteady aerodynamic models for a twodimensional rigid plate undergoing pitching and plunging motion is present in the literature. For a two-dimensional flexible wing, unsteady forces are generated by the wing deflection in time. Hence the necessity of unsteady models that also take into account the flexible degrees of freedom of the wing. In the present work, the deflection of a flexible wing immersed in a uniform free-stream has been decomposed using a truncated Fourier series. The effects of a prescribed deflection of the flexible wing on the flowfield in terms of each one of the leading modes (from 1 to 10) have been investigated using high-fidelity Direct Numerical Simulation (DNS) for viscous, compressible flows at low Reynolds numbers. System identification techniques are applied to obtain reduced order state-space models that relate the deflection of the wing to the measured lift. The system identification procedure is presented and the accuracy and validity of the reduced order models are discussed. Finally, the characteristics and the performance of the reduced order models are addressed from a feedback control point of view.
Treatment options of asthma in infancy

Both beta-2 agonists and anticholinergics are widely used even in young children. Response in the individual is difficult to predict, and a therapeutic trial of either or both is usually legitimate. Paradoxical broncho-constriction with nebulized ipratropium has been reported, probably related to the tonicity of the solution [1]. Bronchodilators can worsen symptoms due to tracheobronchomalacia due to reduction in smooth muscle tone [2]. There is little experience of long-acting beta-2 agonists in this age group.
ColTop: Visual Topic-Based Analysis of Scientific Community Structure

Personal networks formed within scientific communities and the collaborations they yield are one of the driving forces behind innovation and new discoveries. Luckily, successful collaboration produces analyzable data points in the form of publications that allow us to learn and understand some of the connections and collaborative structures in a scientific community. Co-author information is one important aspect of this, and various solutions to the fundamental visualization problems of co- author graphs exist. In this work, we introduce \emph{ColTop}, a multi- level, interactive graph visualization system that allows users to effectively analyze publication data. It combines co- author information with other meta- data and information extracted from textual content to support comprehensive analyses. ColTop includes a novel, heuristics-based approach to create a meaningful abstraction of co-author networks, and enriches them with topic information. To demonstrate the applicability of our approach, we discuss an example analysis scenario based on a practical data set.
The BRENDA Model: Integrating Psychosocial Treatment and Pharmacotherapy for the Treatment of Alcohol Use Disorders

While the U.S. Food and Drug Administration has approved several medications for the treatment of alcohol-related problems, their use has not gained wide acceptance in the United States. Typically, patients with alcohol use disorders are only referred to psychosocial support (e.g., Alcoholics Anonymous). However, the use of pharmacotherapy may complement psychosocial treatments, as evidence shows that pharmacotherapy can improve treatment outcomes. The effectiveness of pharmacotherapy depends on patient compliance with taking the medication and the context in which the medication is administered. BRENDA is a psychosocial program designed specifically to be used by many types of healthcare providers, including primary care clinicians. Designed to enhance medication and treatment compliance, BRENDA is an ideal approach for use in conjunction with pharmacotherapy. The BRENDA approach has 6 components: 1) a biopsychosocial evaluation; 2) a report of findings from the evaluation given to the patient; 3) empathy; 4) addressing patient needs; 5) providing direct advice; and 6) assessing patient reaction to advice and adjusting the treatment plan as needed. This paper describes these components and discusses how the empirical support for each component is linked to the enhancement of medication compliance and the improvement of treatment outcomes.
Citizens' Position in Service Quality Perception. An Approach Analysis in the Case of Spanish Local Administrations

Public sector organizations are not immune to pressure in order to improve their services to citizens. At this point, a major problem is that of “citizen-customer” satisfaction surveys being prone to focus on individuals’ perceptions on service delivery: what the individual think about the quality of delivered service. Authors have usually considered tools like the SERVQUAL scale (useful at measuring service quality in a diverse number of organizations and situations, both in private and public sector spheres) as a prior reference when researching in the quality field, but as being the “source”, then changed (modified) into a more or less “new” proposal. Following this research guideline, in this paper a new model for measuring perceived quality level in local government activities is presented. Three dimensions are suggested for citizens to valuate service quality: technical, functional and overall features.
Developmental Dyslexia: Re-Evaluation of the Corpus callosum in Male Adults

Using a new method based upon the measurement of four angles, we analyzed the corpus callosum of 23 adult male dyslexics and 25 age-matched controls on MRI sagittal scans. Two out of the four angles measured showed significant differences between the groups that are consistent with previous findings concerning the size of the corpus callosum in dyslexics. In particular, posterior regions are concerned, displaying a lowered corpus callosum in dyslexics. These findings are discussed in relation to cortical parietal asymmetries and possible hormonal events, referring to the testosterone hypothesis, that could occur in utero or in the perinatal period in the dyslexic population.