Miracle-dz/UniFAR-FTUs huggingface dataset:
Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 2. Spiro-joined benzofuran, isobenzofuran, and benzopyran piperidines.

Spiro[isobenzofuran-1(3H),4'-piperidines] and the corresponding benzofuran and benzopyran derivatives have been synthesized and evaluated as sigma ligands. The compounds are related to Lu 28-179 (1'-[4-[1-(4-fluorophenyl)-1H-indol-3-yl]-1- butyl]spiro[isobenzofuran-1(3H),4'-piperidine]) that has been demonstrated to be a selective sigma 2 ligand with affinity in the subnanomolar range. The object of the study was to determine the structural factors governing sigma 1/sigma 2 affinity and selectivity within this class of compounds. The N-substituent in spiro[isobenzofuran-1(3H),4'-piperidines] is highly important, both for affinity and selectivity. Spiropiperidines with no or small N-substituents (H, Me, Et) exert very low affinity for both sigma 1 and sigma 2 binding sites (IC50(sigma 1, sigma 2) > 100 nM), whereas medium-sized substituents (e.g., Pr, Bu, Ph(CH2)2) result in potent, but unselective compounds (IC50(sigma 1, sigma 2) = 2-5 nM). Increasing the chain length and the lipophilicity of the N-substituent result in compounds in which high affinity for sigma 2 binding sites is retained and with selectivity for sigma 2 vs sigma 1 binding sites (e.g., 4-cyclohexyl-1-butyl: IC50-(sigma 1) = 1.5 nM, IC50(sigma 2) = 0.07 nM). Introduction of substituents in the benzene ring of the spiro[isobenzofuran-1(3H),4'-piperidine] ring system of Lu 28-179 mainly affects affinity for sigma 1 binding sites. Compounds with substituents (F, CF3) in the 4- or 7-position of the isobenzofuran display high affinity for sigma 2 binding sites (IC50(sigma 2) = 0.5-2 nM) and very low affinity for sigma 1 binding sites (IC50(sigma 1) > 100 nM). Compounds with substituents (F, CF3, Me) in the 5- or 6-position of the isobenzofuran exert increased affinity for sigma 1 binding sites (IC50(sigma 1) = 5-30 nM, IC50(sigma 2) = 0.3-7 nM), thus rendering unselective compounds. Exchanging the isobenzofuran moiety of Lu 28-179 with thioisobenzofuran, benzofuran, or benzopyran also has a pronounced effect on both affinity and selectivity for sigma binding sites. The position of the oxygen atom and the position of the spiroconnection with the 4-position of the piperidine ring were varied, and only compounds in which both the benzene ring and the heteroatom are attached directly to the piperidine ring retain high affinity and selectivity for sigma 2 binding sites (e.g., 3,4-dihydro-1'-[4-[1-(4-fluorophenyl)-1H-indol-3-yl]-1- butyl]spiro[1H-2-benzopyran-1,4'-piperidine]: IC50(sigma 1) = 53 nM, IC50(sigma 2) = 0.9 nM). (ABSTRACT TRUNCATED AT 400 WORDS)
A CMUT probe for medical ultrasonography: from microfabrication to system integration

Medical ultrasonography is a powerful and costeffective diagnostic technique. To date, high-end medical imaging systems are able to efficiently implement real-time image formation techniques that can dramatically improve the diagnostic capabilities of ultrasound. Highly performing and thermally efficient ultrasound probes are then required to successfully enable the most advanced techniques. In this context, ultrasound transducer technology is the current limiting factor. Capacitive micromachined ultrasonic transducers (CMUTs) are micro-electro-mechanical systems (MEMS)-based devices that have been widely recognized as a valuable alternative to piezoelectric transducer technology in a variety of medical imaging applications. Wideband operation, good thermal efficiency, and low fabrication cost, especially for those applications requiring high-volume production of small-area dice, are strength factors that may justify the adoption of this MEMS technology in the medical ultrasound imaging field. This paper presents the design, development, fabrication, and characterization of a 12-MHz ultrasound probe for medical imaging, based on a CMUT array. The CMUT array is microfabricated and packed using a novel fabrication concept specifically conceived for imaging transducer arrays. The performance of the developed probe is optimized by including analog front-end reception electronics. Characterization and imaging results are used to assess the performance of CMUTs with respect to conventional piezoelectric transducers.
Geriatric Syndromes in Older HIV-Infected Adults

Background: Geriatric syndromes such as falls, frailty, and functional impairment are multifactorial conditions used to identify vulnerable older adults. Limited data exist on these conditions in older HIV-infected adults, and no studies have comprehensively examined these conditions. Methods: Geriatric syndromes including falls, urinary incontinence, functional impairment, frailty, sensory impairment, depression, and cognitive impairment were measured in a cross-sectional study of HIV-infected adults aged 50 years and older who had an undetectable viral load on antiretroviral therapy. We examined both HIV and non–HIV-related predictors of geriatric syndromes including sociodemographics, number of comorbidities and nonantiretroviral medications, and HIV-specific variables in multivariate analyses. Results: We studied 155 participants with a median age of 57 (interquartile range: 54–62) and 94% were men. Prefrailty (56%), difficulty with instrumental activities of daily living (46%), and cognitive impairment (47%) were the most frequent geriatric syndromes. Lower CD4 nadir incidence rate ratio [IRR: 1.16, 95% (confidence interval) CI: 1.06 to 1.26], non-white race (IRR: 1.38, 95% CI: 1.10 to 1.74), and increasing number of comorbidities (IRR: 1.09, 95% CI: 1.03 to 1.15) were associated with increased risk of having more geriatric syndromes. Conclusions: Geriatric syndromes are common in older HIV-infected adults. Treatment of comorbidities and early initiation of antiretroviral therapy may help to prevent development of these age-related complications. Clinical care of older HIV-infected adults should consider incorporation of geriatric principles.
Selective over‐expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer

Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1–4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over‐expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1–3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over‐expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over‐expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A Layered Communication Architecture for Power Routing in the Smart Grid

One of the main benefits of the smart grid will be the introduction of Distributed Energy Resources (DERs) into the electricity grid at large scale. These DERs will be able to supply areas with electricity when isolated from the main power grid due to system or equipment failures. Although the integration of DER into the power grid makes the energy supply more reliable and reduces its cost, it creates new issues for distributed network operators (DNOs). While in traditional power grid the electricity usually flows from the central power stations to the consumers, in a modern power grid incremented with DER, the electricity follows in two directions as these new sources of energy are introduced at lower voltages. To introduce DER technology, DNOs will be faced with the challenge of making their distribution power networks more flexible and dynamic. Power routing is an emerging concept that aims at making distribution networks more flexible and dynamic by addressing the technical challenges related to DER. Power routing is predicated on the information availability and coordination which requires a robust and scalable communication. In this paper the authors propose layered communication architecture that facilitates the implementation of power routing in distribution power networks.
Structure of a flavin-binding plant photoreceptor domain: Insights into light-mediated signal transduction

Phototropin, a major blue-light receptor for phototropism in seed plants, exhibits blue-light-dependent autophosphorylation and contains two light, oxygen, or voltage (LOV) domains and a serine/threonine kinase domain. The LOV domains share homology with the PER-ARNT-SIM (PAS) superfamily, a diverse group of sensor proteins. Each LOV domain noncovalently binds a single FMN molecule and exhibits reversible photochemistry in vitro when expressed separately or in tandem. We have determined the crystal structure of the LOV2 domain from the phototropin segment of the chimeric fern photoreceptor phy3 to 2.7-Å resolution. The structure constitutes an FMN-binding fold that reveals how the flavin cofactor is embedded in the protein. The single LOV2 cysteine residue is located 4.2 Å from flavin atom C(4a), consistent with a model in which absorption of blue light induces formation of a covalent cysteinyl-C(4a) adduct. Residues that interact with FMN in the phototropin segment of the chimeric fern photoreceptor (phy3) LOV2 are conserved in LOV domains from phototropin of other plant species and from three proteins involved in the regulation of circadian rhythms in Arabidopsis and Neurospora. This conservation suggests that these domains exhibit the same overall fold and share a common mechanism for flavin binding and light-induced signaling.
Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage.

PURPOSE Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n-3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n-3 fatty acid deficiency, on acute blue-light photochemical damage. METHODS Subjects included eight rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Of these, four had low n-3 fatty acid intake and four had adequate intakes. Control subjects had typical L, Z, and n-3 fatty acid intake. Retinas received 150-μm-diameter exposures of low-power 476-nm laser light at 0.5 mm (∼2°) eccentricity, which is adjacent to the macular pigment peak, and parafoveally at 1.5 mm (∼6°). Exposures of xanthophyll-free animals were repeated after supplementation with pure L or Z for 22 to 28 weeks. Ophthalmoscopically visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage. RESULTS In control animals, the fovea was less sensitive to blue-light-induced damage than the parafovea. Foveal protection was absent in xanthophyll-free animals but was evident after supplementation. In the parafovea, animals low in n-3 fatty acids showed greater sensitivity to damage than animals with adequate levels. CONCLUSIONS After long-term xanthophyll deficiency, L or Z supplementation protected the fovea from blue light-induced damage, whereas adequate n-3 fatty acid levels reduced the damage in the parafovea.
Sensitivities & functional gains for a flexible aircraft-inspired model

Aeroelastic wing micro-autonomous aerial systems (MAAS) concepts are being explored for military and civilian applications. However, on the whole, the issues of control of MAAS are largely unexplored. Controllers designed using methods applicable to larger aircraft are unlikely to realize the agile flight potential of flexible wing MAAS airframes. In this paper, the authors use two Euler-Bernoulli beams connected to a rigid mass to model an aeroelastic wing MAAS. They employ Continuous Sensitivity Equation Methods to examine the sensitivity of the controlled state with respect to variation of the H∞ control parameter, with the primary goal being to gain insight into the flexible dynamics of the system in order to exploit the flexibility for control purposes. Further, the authors examine functional gains in order to determine optimal sensor placement while taking advantage of the flexibility of the MAAS model.
Radiation breakage of human chromosomes in vivo and in vitro.

Chromosomes in the leukocytes from the peripheral blood constitute an almost ideal biological dosimeter: they are readily available for study, they show damage immediately following irradiation, and they also may show radiation changes years after the exposure of the person concerned. The immediate effects are exhibited by cells which were irradiated while circulating in the blood. Since the lifetime of the leukocytes in the blood stream is probably only a few days, the immediate effect should disappear rapidly as they are replaced by new leukocytes. This phenomenon is seen clearly in the work of Tough et al. (1), which showed the disappearance of cells exhibiting radiation damage in a matter of days from the peripheral blood of a patient who received a single dose of partial body irradiation. On the other hand, radiation injury to the precursors of the monocytes and large lymphocytes—the two kinds of leukocyte which can divide—persist probably for the lifetime of the individual. Thus irradiation to the l.
Posttraumatic Stress Disorder in Peacekeepers: A Meta-Analysis

A meta-analysis was conducted to estimate the prevalence of posttraumatic stress disorder (PTSD) among peacekeepers. A systematic review was carried out using Medline, Institute for Scientific Information/Web of Science and Published International Literature on Traumatic Stress databases, leading to a total of 12 studies reporting PTSD estimates. Pooled current PTSD prevalence was 5.3%, ranging from 0.05% to 25.8%, and a metaregression was used to investigate the variables that could account for the lack of homogeneity. However, none of the extracted information was capable of explaining the heterogeneity of the estimates. Peacekeeping studies presented different methodologies such as several screening instruments and different times from the deployment to the moment of PTSD assessment. The wide difference found among those estimates highlights the importance of the creation of standards for PTSD evaluation among peacekeepers.
Queering Genres, Battering Males: The Wife of Bath's Narrative Violence

����� Why does the Wife of Bath tell a romance? This question is virtually a critical clichA©, but for good reason: "The General Prologue," the pilgrims' prologues, and the narratives preceding her tale establish the expectation that she will tell a tale suited to her social class and vocation. As even the most casual reader of The Canterbury Tales cannot help but observe, the speaker of a tale generally chooses a genre that reflects his or her character: in the majority of the tales, the speaker's economic class or vocation relates at least peripherally to the genre of his/her tale.1 The Wife of Bath, however, disrupts this pattern: although her "Prologue" establishes her as a bawdy and raucous figure, on a similar economic level of such other fabliau-tellers as the Miller and the Merchant, she breaks from her socioeconomic position to tell a romance rather than a fabliau. Furthermore, Alison's "Prologue" and "Tale" are virtually surrounded by fabliaux.2 They must follow the texts of the introductory Fragment I, which contains the Miller's and the Reeve's fabliaux, and they immediately precede the fabliaux of Fragment III, "The Friar's Tale" and "The Summoner's Tale. "3 Given her social position, her bawdy temperament, and her place in the overarching narrative of The Canterbury Tales, it seems much more likely that Alison would tell a fabliau than a romance.4
The Influence of Changes in Asset Volatilities and Correlations on Minimum Variance Portfolio Risk

This paper makes a number of contributions to the understanding of minimum variance portfolio (MVP) risk. First, it presents several results connecting changes in MVP risk to changes in portfolio asset volatilities and correlations. Second, it explores the efficacy of three alternative methods of attributing changes in MVP risk to either changes in asset volatility or changes in asset correlations. Lastly, Dow Jones stocks are employed to empirically measure the relative importance of changes these two influences to the dynamics of MVP risk during the period 2001 to 2010 with particular emphasis on the financial crisis years 2008 and 2009.
Supplemental Nutrition Assistance Program participation is associated with an increase in household food security in a national evaluation.

BACKGROUND The Supplemental Nutrition Assistance Program (SNAP) provides nutrition assistance benefits to low-income families in an effort to reduce hunger and improve health and well-being. Because 1 in 7 Americans participate in the program each month, policymakers need to know whether the program is meeting these objectives effectively. OBJECTIVE The objective of this study was to estimate the association between SNAP participation and household food security using recent data from the largest national survey of the food security of SNAP participants to date. METHODS The analysis used a survey of nearly 6500 households and a quasi-experimental research design that consisted of 2 sets of comparisons. Using a cross-sectional sample, we compared information collected from SNAP households within days of program entry with information collected from a contemporaneous sample of SNAP households that had participated for ∼6 mo. Next, using a longitudinal sample, we compared baseline information collected from new-entrant SNAP households with information from those same households 6 mo later. Multivariate logistic regression analysis was used to estimate associations between SNAP and household food security. RESULTS SNAP participation decreased the percentage of SNAP households that were food insecure in both samples by 6-17%. SNAP participation also decreased the percentage of households experiencing severe food insecurity--designated very low food security--by 12-19%. Findings were qualitatively robust to different empirical specifications. CONCLUSION SNAP serves a vital role in improving the health and well-being of households by increasing food security. Given recent legislation to reduce program size and limit program eligibility, this study underscores SNAP's continued importance in affecting households' well-being. Future research is needed to determine whether specific groups of households experience differential improvements in food security.
Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]‐(+)‐PHNO is a D3 receptor preferring agonist in vivo

[11C]PHNO is a recently introduced agonist to image DA D2‐like receptors with Positron Emission Tomography (PET). In cats and humans, [11C]PHNO revealed an atypical distribution compared to radiolabeled D2‐like antagonists (such as [11C]raclopride) or other D2‐like agonists (such as [11C]NPA), as it displayed unusual high binding in the globus pallidus (GP). The goal of this study was to assess the pharmacological nature of the binding of [11C]PHNO in the GP in nonhuman primates. As previously reported in humans, [11C]PHNO equilibrium specific to nonspecific equilibrium partition coefficients (V3″) in baboons was much higher in GP (3.88 ± 1.15) than in the dorsal striatum (DST, 2.07 ± 0.43), whereas the reverse was true for [11C]raclopride (1.48 ± 0.41 in GP, 2.56 ± 0.91 in DST) and [11C]NPA (0.87 ± 0.19 in GP, 1.02 ± 0.13 in DST). Administration of unlabeled raclopride resulted in similar reductions of [11C] PHNO V3″ and [11C]raclopride V3″ in both the GP and the DST. This observation demonstrated that the [11C]PHNO binding in the GP was specific to D2‐like receptors. To evaluate the respective contribution of D3 and D2 receptors to the binding potential (BP) of [11C]PHNO and [11C]raclopride, experiments were carried out with the selective D3 partial agonist 1‐(4(2‐Napthoylamino)butyl)‐4‐(2‐methoxyphenyl)‐1A‐piperazine HCL (BP897). BP897 reduced [11C]raclopride V3″ by 29% ± 9%, 19% ± 8%, and 10% ± 7% in GP, VST, and DST, respectively, a result consistent with expectation from postmortem studies (D3/D2 ratio in GP > VST > DST). BP897 reduced [11C]PHNO V3″ by 57% ± 11%, 30% ± 11%, and 13% ± 8% in GP, VST, and DST, respectively, indicating that the D3 receptor contribution to [11C]PHNO signal is higher than that of [11C]raclopride. From these experiments we conclude that [11C]PHNO is a D3 preferring agonist, and that this property explains the high GP signal not observed with [11C]raclopride or [11C]NPA. This property might contribute to its higher vulnerability to endogenous DA compared to [11C]raclopride and [11C]NPA. Synapse 60:485–495, 2006. © 2006 Wiley‐Liss, Inc.
Characteristics of Newly Formed Bone in Sockets Augmented With Cancellous Porous Bovine Bone and a Resorbable Membrane: Microcomputed Tomography, Histologic, and Resonance Frequence Analysis

Aim:Microcomputed tomography (micro-CT) has become a highly accurate and nonintrusive method for analysis of bone. This study aims to determine the microstructural characteristics of the bone formed in grafted extraction sockets. Methods:This prospective study comprised 10 patients. Cancellous porous bovine bone (CPBB) was used for socket grafting. Ten bone samples were harvested from implant site 9 months after grafting, before implant placement, and histologic and microstructural characteristics were analyzed. Cone-beam computed tomography scans were performed, and implant stability was also determined. Results:Four men and 6 women, with a mean age of 44 years, were included in the study. Micro-CT revealed a compact structure with high bone volume fraction, trabecular thickness and number, but a low trabecular separation and pattern factor, which made it an optimal structure that is expected to resist occlusal loads. Histologic examination revealed an abundant amount of CPBB particles (27.5%) and new bone formation (23.3%) 40.6 months after bone grafting surgery. Moreover, mean implant stability quotient was 75.7 units. Conclusion:This investigation demonstrated marked de novo bone formation after a healing period of 9 months. This trabecular bone had a compact structure with abundant thick trabeculae.