Miracle-dz/UniFAR-FTUs huggingface dataset:
Ex vivo and in vivo evaluation of (2R,3R)‐5‐[18F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Molecular imaging of the vesicular acetylcholine transporter (VAChT) using positron emission tomography (PET) may provide insights into early diagnosis and better understanding of Alzheimer's disease. We further characterized the VAChT ligand (2R,3R)‐5‐FEOBV (1) and developed new fluoropropoxy analogues. Ex vivo studies of the new nonradiolabeled analogues (2R,3R)‐5‐FPOBV (2) (kD = 0.7 nM) and (2S,3S)‐5‐FPOBV (3) (kD = 8.8 nM) were performed in rat brain and showed an enantioselective inhibition of (−)‐5‐[125I]‐IBVM uptake in striatum, cortex, and hippocampus (e.g., 74% for 2 and only 54% for 3 in the cortex). Radiochemical procedures were developed to produce [18F]1 and [18F]2 as potential imaging agent for the VAChT. The radiochemistry was carried out in a one step procedure, with radiolabeling yields of 17 and 2.6% (range: 1–5.4), respectively, nondecay corrected with good specific activity: 124–338 GBq/μmol. The radiochemical purity was greater than 98%. The biological (ex vivo and in vivo) properties of these radioligands were evaluated in rats and showed a low (less then 0.1% of the injected dose) and homogeneous brain uptake. The in vivo PET study of [18F]2 performed in baboon also revealed rapid defluorination as the main problem. Therefore [18F]1 and [18F]2 appear to be unsuitable for in vivo imaging of the VAChT using PET. Synapse 61:962–970, 2007. © 2007 Wiley‐Liss, Inc.
Neuronal activity regulates neurotransmitter switching in the adult brain following light-induced stress

Significance The discovery that neurotransmitter identity is regulated by activity in the adult mammalian brain during a stress response raises questions about the extent and function of this plasticity. Specific synapses are associated with the release of a particular neurotransmitter or transmitters on the basis of evidence obtained under a single set of conditions. Transmitter switching endows the connectome with greater plasticity: Activity-dependent revision of signaling provides another dimension of flexibility to regulate normal behavior. Changes in transmitter identity are also positioned to contribute to diseases of the nervous system. Neurotransmitter imbalance has long been implicated in common neurological and psychiatric disorders, provoking interest in transmitter switching as a therapeutic tool for patients. Neurotransmitter switching in the adult mammalian brain occurs following photoperiod-induced stress, but the mechanism of regulation is unknown. Here, we demonstrate that elevated activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PaVN) in the adult rat is required for the loss of dopamine expression after long-day photoperiod exposure. The transmitter switch occurs exclusively in PaVN dopaminergic neurons that coexpress vesicular glutamate transporter 2 (VGLUT2), is accompanied by a loss of dopamine type 2 receptors (D2Rs) on corticotrophin-releasing factor (CRF) neurons, and can lead to increased release of CRF. Suppressing activity of all PaVN glutamatergic neurons decreases the number of inhibitory PaVN dopaminergic neurons, indicating homeostatic regulation of transmitter expression in the PaVN.
Effects of Dietary Fat and Carbohydrate Exchange on Human Energy Metabolism

Short-term effects of low-fat (10% fat energy), mixed (30% fat energy), and high-fat (50% fat energy) diets on 24-h energy expenditure, and on its components sleeping metabolic rate, diet induced thermogenesis and energy expenditure for physical activity were studied for 3 days using a respiration chamber in twelve normal-weight female volunteers classified as restrained or unrestrained eaters. There were no significant differences in any of the four measures between the restrained and unrestrained eating subjects on any of the diets. Within the group of restrained eaters, 24-h energy expenditure was significantly decreased during consumption of the mixed diet (8.21 +/- 0.21 MJ/d; p < 0.01) and tended to be decreased on the high-fat diet (8.22 +/- 0.25 MJ/d; p = 0.055), relative to the low-fat diet (8.58 +/- 0.21 MJ/d). Diet composition had no effect on 24-h energy expenditure in the women with unrestrained eating. The results suggest that a low-fat diet would be beneficial in the treatment of obesity, especially if subjects have a restrained type of eating behaviour.
Molecular basis for defective secretion of the Z variant of human alpha-1-proteinase inhibitor: secretion of variants having altered potential for salt bridge formation between amino acids 290 and 342

Human alpha-1-proteinase inhibitor (A1PI) deficiency, associated with the Z-variant A1PI (A1PI/Z) gene, results from defective secretion of the inhibitor from the liver. The A1PI/Z gene exhibits two point mutations which specify amino acid substitutions, Val-213 to Ala and Glu-342 to Lys. The functional importance of these substitutions in A1PI deficiency was investigated by studying the secretion of A1PI synthesized in COS cells transfected with A1PI genes altered by site-directed mutagenesis. This model system correctly duplicates the secretion defect seen in individuals homozygous for the A1PI/Z allele and shows that the substitution of Lys for Glu-342 alone causes defective secretion of A1PI. The substitution of Lys for Glu-342 eliminates the possibility for a salt bridge between residues 342 and 290, which may decrease the conformational stability of the molecule and thus account for the secretion defect. However, when we removed the potential to form a salt bridge from the wild-type inhibitor by changing Lys-290 to Glu (A1PI/SB-290Glu), secretion was not reduced to the 19% of normal level seen for A1PI/Z-342Lys; in fact, 75% of normal secretion was observed. When the potential for salt bridge formation was returned to A1PI/Z-342Lys by changing Lys-290 to Glu, only 46% of normal secretion was seen. These data indicate that the amino acid substitution at position 342, rather than the potential to form the 290-342 salt bridge, is the critical alteration leading to the defect in A1PI secretion.
Organization of repeated regions within the Epstein-Barr virus DNA molecule

Virions of human Epstein-Barr virus released from the B95-8 line of marmoset lymphoblasts have linear double-stranded DNA molecules of 115 x 10(6) molecular weight (180 +/- 10 kilobase pairs). Approximately 20% of this DNA yields multiple fragments of 3,200 base pairs when cleaved with any one of the BglII, BamHI, PvuII, SacI, SstII, or XhoI restriction enzymes. The results of cleavage site mapping with these and other enzymes, together with blot hybridization experiments using the 3.2-kilobase pair BglII-R fragment as a probe, indicate that these fragments originate from an internal region between 0.710 and 0.915 map units containing a cluster of at least 12 apparently identical repetitions of a sequence with relatively high guanine plus cytosine content. The repeat units are arranged in adjacent tandem array with all copies having the same orientations, and they form a series of oligomers of tailed double-stranded circles when fragments containing portions of the cluster are denatured and reannealed. Physical maps of cleavage sites within the 3.2-kilobase pair repeat units and in the flanking sequences surrounding the repeat cluster have been constructed. We conclude that the Epstein-Barr virus DNA molecule, like those of other mammalian herpesviruses, may be regarded as being divisible into a large L segment and a smaller S segment. However, the detailed arrangement of repetitive sequences within the Epstein-Barr virus S segment differs significantly from that in all other herpesvirus genomes described so far.
Identification and Characterisation of C1q-Binding Phage Displayed Peptides

Five phage displayed peptide libraries were screened for binders to C1q, the recognition subunit of the classical complement pathway. Two rounds of panning resulted in the isolation and characterisation of several different phage displayed C1q-binding peptides from all five libraries. Two groups of the characterised peptides show sequence similarity with part of the metal ion dependent adhesion site (MIDAS) of integrin A-domains, and the site 187LRNPCPNKEKECQPPF of CD18 (integrin beta2), respectively. These results support binding of complement receptor 3 (CR3, CD11b/CD18, Mac1) to C1q and further suggest C1q binding sites in CR3. We also discuss sequence matches between the characterised peptides and proteins known to interact with C1q, as well as other proteins listed in the SwissProt databank. These findings are of interest for the study of the complement system and may lead to the development of peptides, fusion products or peptido-mimetics with C1q modulating potential.
Don’t be a flamin’ fool: Effectiveness of an adult burn prevention media campaign in two regions in Queensland, Australia—An interventional study

BACKGROUND Major burn injuries cause devastating physical and psychosocial morbidity, combined with significant health care and community costs. The aim of this study was to evaluate the effectiveness of a targeted burn prevention message on burn safety knowledge and behavior. METHODS An 11-year retrospective review of patients admitted to an adult tertiary burn center identified flammable liquid burn injuries in males older than 15 years as 23% of admissions and the most common preventable injury. Burn safety knowledge and experience were measured in a single-blinded, controlled, restricted (male, >15 years), interventional, (therapeutic) prevention study using a total of 2,053 computer-assisted telephone interviews in an intervention region (IR) and control region. A two-week multimedia campaign with the theme “Don’t Be a Flamin’ Fool” was delivered in the IR. RESULTS The preintervention survey revealed that 13% (218 of 1,637) reported having previously had a gasoline (petrol) burn. Following the intervention, there was a higher percentage of respondents in the IR that had seen or heard a burn prevention message in the previous 3 months (51% vs. 10%; p < 0.001) and perceived that gasoline was a danger when used to start a fire (97% vs. 91%; p = 0.001), that any volume of gasoline was unsafe (85% vs. 65%; p < 0.001), and that gasoline can explode (96% vs. 92%; p = 0.001). Awareness and memory reverted to preintervention levels at 12 months. Eighty-three percent of respondents (100 of 120) who had seen the “Flamin’ Fool” campaign thought it was effective in getting its message across. CONCLUSION This collaborative study found that a media prevention message had a significant impact on burn safety knowledge, which diminished over time.
Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia

The BZLF1 protein of Epstein-Barr virus (EBV) is a key immediate-early protein which has been shown to disrupt virus latency in EBV-infected B cells. We have generated a monoclonal antibody, BZ1, to BZLF1 which reacts in immunohistology, immunoblotting, and immunoprecipitation and which recognizes both the active, dimeric form and the inactive, monomeric form of the protein. Biopsies of oral hairy leukoplakia, an AIDS-associated lesion characterized by high-level EBV replication, were examined by immunohistochemistry using the BZ1 monoclonal antibody. A differentiation-associated pattern of BZLF1 expression was observed, BZ1 reacting with nuclei of the upper spinous layer of the lesion. This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation. A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication. The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium.
Two-Country Segmented and Partially Segmented Market Cross-section Regression (CSR) Test Specification and Inference

Empirical methods of Shanken (1992) are extended to the case in which different factors are related to particular countries' security expected returns. We show that Shanken's "three-pass Gauss-Newton" estimator is both consistent and asymptotically efficient. This estimator is analogous to Gibbon's (1982) multivariate regression method (MVRM), and heteroskedasticity and autocorrelation adjustments to this method are discussed. As an alternative to full maximum likelihood estimation or its robust variants, the linearized method that we develop will, minimally, be useful for both determining reasonable parameter starting values and for pre-screening higher dimensional model alternatives. We also find that Shanken's consistent and asymptotically efficient integrated market two-pass covariance estimator is not asymptotically efficient in the segmented markets case.
Zero Lower Bound Risk and Long-Term Inflation in a Time Varying Economy

Using a Time Varying Parameters Vector Auto Regression framework, I construct an index, the Zero Probability Index (ZPI), based on the probability of the nominal interest rate hitting the zero lower bound (ZLB) within 10 quarters. I show how the probability of reaching the ZLB evolves over time and measure how a rise in the inflation target can reduce this probability. High ZPI episodes tend to occur during recessions and are c by a combination of the initial state of the variables and the estimated volatility of the shocks. However, not all episodes of a high ZPI share the same causes. In the US recessions of the 1980s, the probability was influenced significantly by an exceptionally volatile environment that overcame the dampening influence of the period’s high nominal interest rates. On the other hand, the high ZPI for the 2001 and 2007 recessions were mainly defined by an initial state of low interest rates. Because of this difference, an increase in the inflation target was much more effective in reducing the estimated probability of the interest rate reaching the ZLB in the latter episodes.
The Process of Coping with Domestic Violence in Adult Survivors of Childhood Sexual Abuse

ABSTRACT Research suggests that the use of disengaged or avoidant strategies to cope with interpersonal violence contributes to the development of depressive symptoms and other psychological difficulties. Survivors of childhood sexual abuse (CSA) who are exposed to subsequent episodes of abuse may be more likely to rely on disengaged coping strategies, placing them at elevated risk of psychological symptomatology. In this study, we explored the interrelationships between coping, depression, and self-esteem in an ethnically diverse sample of domestic violence survivors (N = 219) with and without a history of CSA. As predicted, CSA survivors (n = 86) reported significantly greater use of disengaged coping strategies (wishful thinking, self-criticism, and social withdrawal) than non-CSA survivors (n = 133). As hypothesized, both a CSA history and the use of disengaged coping significantly predicted higher levels of depression and lower self- esteem. Clinical implications of the findings are discussed.
Time-shift estimation and focusing through distributed aberration using multirow arrays

The effects of element height on time-shift estimation and transmit focus compensation are demonstrated experimentally. Multirow ultrasonic transducer arrays were emulated by combining adjacent elements of a 3.0-MHz, 0.6-mm pitch, two-dimensional array to define larger virtual elements. Pulse-echo data were acquired through tissue-mimicking distributed aberrators, and time-shift maps estimated from those data were used for transmit focus compensation. Compensated beams formed by arrays with fine row pitches were similar, but focus restoration was significantly less effective for "1.75-D" arrays with a coarse row pitch. For example, when focus compensation was derived from strongly aberrated random scattering data [70-ns nominal rms arrival time fluctuation with 7 mm FWHM (full-width at half-maximum) correlation length], the mean -20 dB lateral beamwidths were 5.2 mm for f/2.0 arrays with 0.6- and 1.8-mm row pitches and 9.5 mm for an f /2.0 array with 5.4-mm pitch. Time-shift maps estimated from random scattering data acquired with 5.4-mm pitch arrays included large discontinuities caused by low correlation of signals received on vertically and diagonally adjacent emulated elements. The results indicate that multirow arrays designed for use with aberration correction should have element dimensions much less than 75% of the correlation length of the aberration and perhaps as small as 25 to 30% of the correlation length.
Subclinical atherosclerosis among rheumatoid arthritis patients without overt cardiovascular risk factors

Abstract Objective. To determine the associated factors of subclinical atherosclerosis measured with carotid intima media thickness (CIMT) among rheumatoid arthritis (RA) patients without any overt traditional cardiovascular (CV) risk factors. Methods. Forty RA patients with matched age and gender healthy controls were recruited. Carotid ultrasound was performed to all subjects. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex reference values. Univariate and multivariate analyses were performed to determine the association between the sociodemographics and disease characteristics of RA with thickened CIMT. Results. Abnormally thickened CIMT were observed in 11 RA patients (27.5%) and in 4 control subjects (10%), p = 0.04. It was highly prevalent among RA patients with active disease (54.5% vs 17.2%), p = 0.02. Patients with thickened CIMT also tend to have erosive disease, p = 0.06. Seropositive rheumatoid factor (RF) patients also had significantly higher CIMT values as compared with sero-negative patients, p = 0.03. Multivariable logistic regression analysis revealed that active disease was independently associated with thickened CIMT. Conclusions. RA patients are at risk for subclinical atherosclerosis despite absence of traditional CV risk co morbidities and active disease was the independent factor associated with it.
Protein S levels modulate the activated protein C resistance phenotype induced by elevated prothrombin levels

Summary Elevated plasma prothrombin levels, due to the prothrombin 20210 G/A mutation or to acquired causes, area risk factor for venous thrombosis,partly because of prothrombin-mediated inhibition of the protein C anticoagulant pathway and consequent activated proteinC (APC) resistance. We determined the effect of plasma prothrombin concentration on the APC resistance phenotype and evaluated the role of protein S levels asa modulating variable. The effect of prothrombin and protein S levels on APC resistance was investigated in reconstituted plasma systems and in a population of healthy individuals using both the aPTT-based and the thrombin generation-based APC resistance tests. In reconstituted plasma, APC resistance increased at increasing prothrombin concentration in both assays. Enhanced APC resistance was caused by the effect of prothrombin on the clotting time in the absence of APC in the aPTT-based test, and on thrombin formation in the presence of APC in the thrombin generation-based test. In plasma from healthy individuals prothrombin levels were highly correlated to protein S levels. Since prothrombin and proteinS had opposite effects on the APC resistance phenotype, the prothrombin/protein S ratio was a better predictor of APC resistance than the levels of either protein alone. Prothrombin titrations in plasmas containing different amounts of proteinS confirmed that proteinS levels modulate the ability of prothrombin to induce APC resistance. These findings suggest that carriers of the prothrombin 20210 G/A mutation, who have a high prothrombin/protein S ratio, may experience a higher thrombosis risk than non-carriers with comparable prothrombin levels.
Barriers to Implementing Common Principles of Interagency Collaboration. Lessons Learned from the Marin City Families First Program.

Marin City Families First (MCFF) provides advocacy and case management for 25 residents of Marin City (Marin County, California) with young children as it works to develop service and decision-making links among community agencies and networks. In this report, principles that relate to the successful delivery of comprehensive community-based child and family services are outlined, and barriers to strategies for intervention and collaboration are revealed through interviews with program directors and line workers. The focus is on barriers in the areas of: (1) collaborative case management and service integration; (2) collaborating in an ethnically diverse community; (3) collaborating with funders; and (4) collaborating with community developers. These barriers are discussed from the perseectives of those interviewed. Whenever possible insights and suggestions for improvement are made. Reflection on the barriers that impede successful service delivery can help others anticipate problems and structure tglys to enhance their own local efforts in family support and community development. (SLD) *********************************************************************** Reproductions supplied by EDRS are the best that can be made from the original document. ***********************************************************************
Awareness of Publication Guidelines and the Responsible Conduct of Research

We have conducted a longitudinal survey of NIH-funded F32 postdoctoral fellows to determine if mandated instruction in the responsible conduct of research (RCR) has measurable effects on awareness of, attentiveness to, and behavioral judgments about research ethics and authorship and publication. Of 418 F32 fellows participating in the study, 50% were aware of and had referred to guidelines on authorship and publication practices while 50% were either unaware of or had not referred to guidelines. Groups were similar with regard to total number of peer-reviewed publications and total number of first author publications, years of research experience, years since completing their doctoral degree, and receipt of RCR training. The equal distribution of guideline awareness and use, and group similarities with regard to career development and achievement provided us with an opportunity to consider whether awareness of and use of guidelines is associated with broader judgments about author roles and responsibilities. The findings suggest that awareness and utilization of guidelines are, at best, only modestly associated with more ethically appropriate judgments and attitudes about author roles and responsibilities among novice F32’s. K.A. B. , C.L. F. , and F.L. M. designed the survey instrument. K.A. B. oversaw data collection, and K.A. B. and C.L. F. performed data compilation and statistical analysis. All three authors participated equally in data interpretation. K.A. B. wrote the first draft of the Methods and Results section and F.L. M. wrote the Introduction section and performed the literature search. All authors co-wrote and co-edited the Discussion section. None of the authors have any financial, personal, or institutional conflicts of interest related to the performance of this research or the reporting of its results. This research was carried out under a human subject research protocol, reviewed and approved by the Virginia Commonwealth University Institutional Review Board (VCU IRB # 2826; current approval date, 5/12/04) This research was supported by the Research on Research Integrity Program, an ORI/NIH collaboration: USPHS Grant NS042494 to Virginia Commonwealth University (F.L.M., Principal Investigator). We gratefully acknowledge the assistance of William E. McGarvey and Walter Schaffer, Office of the Director, National Institutes of Health.