Miracle-dz/UniFAR-FTUs huggingface dataset:
Photolysis of the Carbon Monoxide Complex of Myoglobin: Nanosecond Time-Resolved Crystallography

The biological activity of macromolecules is accompanied by rapid structural changes. The photosensitivity of the carbon monoxide complex of myoglobin was used at the European Synchrotron Radiation Facility to obtain pulsed, Laue x-ray diffraction data with nanosecond time resolution during the process of heme and protein relaxation after carbon monoxide photodissociation and during rebinding. These time-resolved experiments reveal the structures of myoglobin photoproducts, provide a structural foundation to spectroscopic results and molecular dynamics calculations, and demonstrate that time-resolved macromolecular crystallography can elucidate the structural bases of biochemical mechanisms on the nanosecond time scale.
Evolution of MHC Class II E Diversity Within the Genus Peromyscus

Progress in understanding the evolution of variation at the MHC has been slowed by an inability to assess the relative roles of mutation vs. intragenic recombination in contributing to observed polymorphism. Recent theoretical advances now permit a quantitative treatment of the problem, with the result that the amount of recombination is at least an order of magnitude greater than that of mutation in the history of class II genes. We suggest that this insight allows progress in evaluating the importance of other factors affecting the evolution of the MHC. We investigated the evolution of MHC class II E sequence diversity in the genus Peromyscus. We find evidence for extensive recombination in the history of these sequences. Nevertheless, it appears that intragenic recombination alone is insufficient to account for evolution of MHC diversity in Peromyscus. Significant differences in silent variation among subgenera arose over a relatively short period of time, with little subsequent change. We argue that these observations are consistent with the effects of historical population bottleneck(s). Population restrictions may explain general features of MHC evolution, including the large amount of recombination in the history of MHC genes, because intragenic recombination may efficiently regenerate allelic polymorphism following a population constric-
Influence of the Nonergot Dopamine Agonist Piribedil on Vigilance in Patients With Parkinson Disease and Excessive Daytime Sleepiness (PiViCog-PD): An 11-Week Randomized Comparison Trial Against Pramipexole and Ropinirole

Objectives The aim of this study was to investigate the effects of piribedil on vigilance and cognitive performance in patients with Parkinson disease experiencing excessive daytime sleepiness on pramipexole or ropinirole. Methods In this 11-week randomized, active-controlled, rater-blinded phase III study, eligible patients were randomly assigned to either receive piribedil or to continue on pramipexole or ropinirole. The primary outcome was the median reaction times during the second 15 minutes of the subtest “vigilance” of the Test battery for Attention Performances (TAP). Secondary outcomes included the Epworth Sleepiness Scale, Unified Parkinson’s Disease Rating Scale, neuropsychological testing, and items of the Clinical Global Impression. Results Forty-four patients received piribedil; 36 continued on either pramipexole or ropinirole. There was no difference in the primary end point reaction time of the TAP subtest vigilance between piribedil and the comparator (996 vs 954 milliseconds, P = 0.68). Piribedil reduced daytime sleepiness with lower Epworth Sleepiness Scale scores at the end of treatment compared with the comparator (−4 vs −2 points; P = 0.01). The median Unified Parkinson’s Disease Rating Scale III score at the end of treatment was comparable between the 2 groups. Neuropsychological tests revealed no significant between-treatment differences. A higher therapeutic effect and global improvement were shown by the Clinical Global Impression of piribedil-treated patients. Conclusions This study shows that switching from pramipexole or ropinirole to piribedil has no effect on the reaction time of the TAP subtest vigilance but upholds the same therapeutic motor effect and reduces daytime sleepiness to a clinically relevant degree in patients with excessive daytime sleepiness.
The autophagy machinery is required to initiate hepatitis C virus replication

In addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. To counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. Here, we report that autophagy proteins (i.e., Beclin-1, Atg4B, Atg5, and Atg12) are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but they are not required once infection is established. These results illustrate a previously unappreciated role for autophagy in the establishment of a viral infection and they suggest that different host factors regulate the translation of incoming viral genome and translation of progeny HCV RNA once replication is established.
Near-Surface-Mounted Fiber-Reinforced Polymer Reinforcements for Flexural Strengthening of Concrete Structures

Use of fiber-reinforced polymer (FRP) materials to strengthen bridges has been adopted extensively in the last decade. FRP has been used in different configurations and techniques to use the material effectively and to ensure long service life of the selected system. One of these innovative strengthening techniques is near-surface mounting (NSM) that consists of placing FRP reinforcing bars or strips into grooves precut into the concrete cover in the tension region of the strengthened concrete member. This method is relatively simple and considerably enhances the bond of the mounted FRP reinforcements, thereby using the material more effectively. This paper presents test results of reinforced concrete (RC) T-beams strengthened in flexure with different strengthening systems using FRP reinforcing bars and strips as NSM reinforcement and externally bonded FRP strips. The FRP reinforcements used in this investigation include carbon FRP (CFRP) reinforcing bars and strips and glass FRP (GFRP) thermoplastic strips. Behavior and effectiveness of the materials used for the various strengthening systems are compared. The structural performance and modes of failure of the tested beams are presented and discussed. Test results indicated that using NSM FRP reinforcing bars and strips is practical, significantly improves the stiffness, and increases the flexural capacity of RC beams. The limitations of using NSM FRP reinforcing bars and strips are controlled by serviceability requirements in terms of overall deflections and crack widths rather than delamination, observed by many researchers, of externally bonded FRP reinforcement. Strengthening of RC beams using NSM FRP strips provided higher strength capacity than externally bonded FRP strips using the same material with the same axial stiffness.
Targeted expression of anoctamin calcium-activated chloride channels in rod photoreceptor terminals of the rodent retina.

PURPOSE In the vertebrate retina, calcium-activated chloride channels are expressed in photoreceptor synaptic terminals. These channels are involved in the control of transmitter release in the dark. The search for their molecular identity has recently lead to the localization of the protein anoctamin 2 (also TMEM16B) in the outer plexiform layer of the rodent retina. Since both rod and cone photoreceptors have their terminals in this layer, it was not clear which of these express anoctamin 2. Here, we examine rod spherules and cone pedicles for expression of anoctamin 2. METHODS Expression of anoctamin genes was studied in the rat eye using RT-PCR. Immunohistochemical experiments were used to localize anoctamins and chloride transporters with their regulatory kinases. Photoreceptor synaptic proteins, as well as the lectins Peanut agglutinin and Griffonia simplicifolia agglutinin, were used to distinguish retinal structures. RESULTS Anoctamin 1, 2, and 10 were found to be expressed in the eye. Anoctamin 2 was expressed as a splice variant that includes exon 15 of the genomic structure. The protein is exclusively expressed in rod terminals and is not present in cone pedicles. Expression is not clustered at the ribbon complex, but spread across the presynaptic membrane where it colocalizes with the plasma membrane calcium pump. The electroneutral chloride transporter NKCC1 is expressed in photoreceptor terminals, together with its regulatory kinases SPAK and OSR1. CONCLUSIONS Rod photoreceptor terminals possess the molecular machinery for chloride accumulation and for the generation of calcium-dependent chloride currents conducted through anoctamin 2 channels. We discuss this finding in the framework of the established hypothesis that calcium-activated chloride channels are part of a feedback inhibition mechanism that limits transmitter release in the dark.
Attachment Styles, Coping Strategies, and Romantic Feelings Among Battered Women in Shelters

The aim of the study was to examine coping strategies, attachment styles, and romantic feelings among a sample of battered women (BWS) in shelters in Israel compared with a sample of women recruited from the community (CS; defined as nonbattered women). Results indicate that BWS were significantly more anxious and avoidant than CS and their romantic feelings for their partners were lower. However, contrary to prediction, BWS used more problem-focused than emotion-focused coping. Also contrary to prediction, attachment style and romantic feelings predicted problem-focused coping among BWS while predicting emotion-focused coping among CS. Aside from challenging common assumptions, the findings of the current study enhance our understanding of the associations between coping style, attachment style, and emotions experienced by BWS and highlight the importance of considering the larger context within which an individual instance of leaving occurs. Even so, future studies should employ a longitudinal design so as to shed additional light on interrelationships between these variables.
Reduced specialist time with direct computed tomography for suspected lung cancer in primary care.

INTRODUCTION Lung cancer (LC) is the most common cause of cancer death in Denmark, and triaging patients through fast-track diagnostic pathways is recommended to improve patient outcome. Data on the most efficient triage organisation of such pathways are limited. The aim of this study was to test a strategy of a straight-to-test model for patients referred to the fast-track pathway. Outcomes were number of computed tomographies (CT) performed, use of specialist time and staff acceptability. MATERIAL AND METHODS We performed a randomised controlled study enrolling 493 patients who were referred from general practice to fast-track LC evaluation (1 January-1 December 2012). Half of the patients were randomly assigned to the intervention and went straight to a chest CT before chest-physician evaluation. Time was measured for patients at random days. Acceptability was examined in a focus group interview. RESULTS In the intervention group, 95.5% of patients had a CT performed compared with 97.2% in the control group. There was no difference in the number of CTs between the groups (risk difference (RD) = 1.3% (95% confidence interval (CI): 4.4-2.0; p = 0.454)). In the intervention group, chest-physician time was 13.3 min. (min.-max.: 7.7-19.5 min.) lower per referred patient than in the control group. CONCLUSION Giving general practitioners direct access to a CT did not change the number of CTs performed and significantly reduced chest-physician time per patient. In addition, the strategy was associated with high levels of staff acceptability. FUNDING The project was supported by the Danish Cancer Research Foundation, the Danish Cancer Society and the Novo Nordisk Foundation. TRIAL REGISTRATION ClinicalTrials.gov: NCT01779726.
Greenhouse gas emission reduction potentials in air transport: a structural equation modelling-based multi-group analysis

ABSTRACT In this study, we used a structural equation modelling (SEM) approach to identify the key factors that influence greenhouse gas (GHG) emission reduction potentials in air transport (ERPAT). We explored the correlations among constructs from the perspectives of aviation GHG emission reduction. Organisation type is one of the contextual factors that may change the nature of these correlations. Person- and self-administered questionnaires were used to collect data from 249 aviation experts. The results obtained using SEM showed that aircraft technology and design, aviation operations and infrastructure, socio-economic and policy measures, and alternative fuels and fuel properties are the key factors for reducing GHG emission. Conclusively, organisation type can help in controlling the relationship among the constructs. Thus, organisation type acts as a moderator in the research model. The outputs can be used to measure the level of knowledge and understanding regarding ERPAT and can provide policy-makers, government organisations, and airlines with valuable information for designing appropriate air transport policies for emission reduction.
Preparation of single-cell suspensions from normal liver, regenerating liver, and Morris hepatomas 9121 and 5123tc.

Suspensions of single cells were prepared from normal adult rat liver either by mincing the tissue and incubating it in various concentrations of sodium tetraphenylborate, ethylene-diaminetetraacetate, and 0.1% hyaluronidase plus 0.05% collagenase or by continuous recirculating perfusion of the liver with 0.1% hyaluronidase plus 0.05% collagenase. Only the latter method produced cells in good yield that were not stained with trypan blue. Incorporation of l-leucine-1-14C into protein was up to 60 times higher in cells prepared by continuous perfusion with hyaluronidase plus collagenase than in cells prepared by incubation of the minced tissue in sodium tetraphenylborate or in hyaluronidase plus collagenase. Liver cells prepared by continuous perfusion had a better preserved ultrastructure than cells obtained by the other methods. In regenerating liver, cells that were not stained with trypan blue were obtained by the two methods with hyaluronidase plus collagenase, the yield being highest after continuous perfusion. In Morris hepatomas 9121 and 5123tc, continuous perfusion could not be established. However, mincing the tissue and incubating it in hyaluronidase plus collagenase yielded cells with an intact ultrastructure. Those cells excluded trypan blue. The amount of the incorporation of l-leucine-1-14C into protein was about 300 times higher than in cells prepared by sodium tetraphenylborate.
How health care regionalisation in Italy is widening the North–South gap

Abstract The Italian National Health Service began experimenting with a significant regionalisation process during the 1990s. The purpose of this article is to assess the effects that this regionalisation process is having on the rift between the north and the south of the country. Has the gap between the health care systems of the northern and southern regions been increasing or decreasing during the 1999–2009 decade? Three indicators will be utilised to answer this question: (1) the level of satisfaction expressed by the citizens towards the regional hospital system; (2) the mobility of the patients among regions; (3) the health care deficit accumulated by the individual regions. On the basis of these three indicators, there is evidence to conclude that, during the decade under study, the gap between the North and the South, already significant, has increased further.
Exploring the use of social comparison by individuals recovering from traumatic brain injury

Objective: To explore if and how individuals with traumatic brain injury (TBI) use social comparison during adjustment to disability. It was hypothesized that comparison activity may change with time since injury. Methods: Fifty-eight participants with TBI were surveyed within 1 or 6 months of discharge from inpatient rehabilitation. Group responses to instruments measuring social comparison and other measures of emotional and physical functioning were compared. Results: Both groups expressed a need for social comparison at a rate comparable to non-clinical populations. The group surveyed at 6 months expressed a greater need for social comparison and scored lower on a measure of mental health, as compared to the group surveyed earlier. Conclusions: Individuals with TBI appear to successfully use social comparison, at least early in recovery, with a possible reduction in effectiveness of use with increased time from injury. Possible mediating factors and implications for adjustment and future study are discussed.
Perceived sleep quality among edentulous elders.

BACKGROUND Anatomical changes associated with edentulism are thought to disturb seniors' sleep. OBJECTIVES (1) To determine sleep quality and daytime sleepiness of edentulous elders. (2) To examine the association between oral health-related quality of life and sleep quality. METHODS Data were collected at a 1-year follow-up from 173 healthy edentulous elders who had participated in a randomised controlled trial and randomly received two types of mandibular prosthesis. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI, range 0-21), with higher scores indicating poorer sleep quality. The Epworth Sleepiness Scale (ESS) was used to measure the level of perceived daytime sleepiness, and scores ≥10 indicated sleepiness. RESULTS The mean global PSQI and ESS scores were 4.7 ± 3.5 and 5.3 ± 3.9. There were no differences in sleep quality or sleepiness between those who wore their dentures at night and those who did not. Elders with frequent denture problems were sleepier during the day than those with fewer problems (p = 0.0034). General health (p = 0.02) and oral health-related quality of life (p = 0.001) are significant predictors of sleep quality. CONCLUSION Healthy edentulous elders, independent of nocturnal wearing of their prosthesis, are good sleepers. Maintaining high oral health quality of life could contribute to better sleep.
Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons

Neuronal differentiation often requires target-derived signals from the cells they innervate. These signals typically activate neural subtype-specific genes, but the gene regulatory mechanisms remain largely unknown. Highly restricted expression of the FMRFa neuropeptide in Drosophila Tv4 neurons requires target-derived BMP signaling and a transcription factor code that includes Apterous. Using integrase transgenesis of enhancer reporters, we functionally dissected the Tv4-enhancer of FMRFa within its native cellular context. We identified two essential but discrete cis-elements, a BMP-response element (BMP-RE) that binds BMP-activated pMad, and a homeodomain-response element (HD-RE) that binds Apterous. These cis-elements have low activity and must be combined for Tv4-enhancer activity. Such combinatorial activity is often a mechanism for restricting expression to the intersection of cis-element spatiotemporal activities. However, concatemers of the HD-RE and BMP-RE cis-elements were found to independently generate the same spatiotemporal expression as the Tv4-enhancer. Thus, the Tv4-enhancer atypically combines two low-activity cis-elements that confer the same output from distinct inputs. The activation of target-dependent genes is assumed to 'wait' for target contact. We tested this directly, and unexpectedly found that premature BMP activity could not induce early FMRFa expression; also, we show that the BMP-insensitive HD-RE cis-element is activated at the time of target contact. This led us to uncover a role for the nuclear receptor, seven up (svp), as a repressor of FMRFa induction prior to target contact. Svp is normally downregulated immediately prior to target contact, and we found that maintaining Svp expression prevents cis-element activation, whereas reducing svp gene dosage prematurely activates cis-element activity. We conclude that the target-dependent FMRFa gene is repressed prior to target contact, and that target-derived BMP signaling directly activates FMRFa gene expression through an atypical gene regulatory mechanism.
Course and Prognosis in Rheumatoid Arthritis *

In a previous communication (Duthie, Thompson, Weir, and Fletcher, 1955), the results of treatment in hospital and the subsequent progress of a group of patients with rheumatoid arthritis were described. At the time of the first report the mean duration of follow-up was 24-4 months. Certain factors which might influence prognosis were considered. It was concluded that improvement following treatment in hospital was reasonably well maintained in the majority of patients if subsequent medical and social supervision were adequate. The most important factors in prognosis proved to be the duration of disease on admission, sex, and type of course run up to the time of admission. Patients admitted within one year of the onset of symptoms fared substantially better than those admitted at a later stage of the disease; the prognosis in males was better than in females; an acute onset followed by
A new SGK1 knockout mouse.

the serum and glucocorticoid- regulated Kinase (SGK1) is a component of the pathway mediating activation of the epithelial sodium channel, ENaC, in the aldosterone-sensitive distal nephron (ASDN). Aldosterone is released when the body needs more sodium or when blood pressure is low, leading to