Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Analysis of the Human Endothelial Nitric Oxide Synthase Promoter

To gain insights into the mechanisms of endothelial nitric oxide synthase (eNOS) gene expression, we have cloned the eNOS promoter and fused it to a luciferase reporter gene to map regions of the promoter important for basal transcription in bovine aortic endothelial cells (BAEC). Transfection of BAEC with F1 luciferase (LUC) (−1600 to +22 nucleotides) yielded a 35-fold increase in promoter. Progressive deletion from −1600 to −1033 (F2 and F3 LUC) did not significantly influence eNOS promoter activity. Further deletion from −1033 to −779 (F4 LUC) resulted in an approximate 40% reduction in basal promoter activity, and still further deletion from −779 to −494 (F5 LUC) did not markedly influence activity. Deletion from −494 to −166 (F6 LUC) reduced eNOS promoter activity by 40-50%. Specific mutation of the consensus GATA site(−230) in the F3 LUC construct reduced luciferase activity (by 25-30%). Gel shift analysis and antibody depletion using BAEC nuclear extracts demonstrated in vitro binding of GATA-2 to the oligonucleotide sequence containing the −230 GATA site. Next, we mutated the Sp1 site(−103) in the F3 and F6 LUC constructs and in the F3 GATA mutant construct. Expression of these Sp1 mutants in BAEC resulted in a 85-90% reduction in normalized luciferase activity. Gel shift and antibody supershift analysis using a BAEC nuclear extracts demonstrated four specific, DNA-protein complexes binding to the eNOS Sp-1 site, with the slowest migrating form composed of Sp1 and another nuclear protein. These data demonstrate that the Sp1 site is an important cis-element in the core eNOS promoter.
The Contemporary Practice of Psychiatric Surgery: Results from a Global Survey of Functional Neurosurgeons

Background: Interest in neurosurgery for psychiatric diseases (NPD) has grown globally. We previously reported the results of a survey of North American functional neurosurgeons that evaluated general attitudes towards NPD and the future directions of the field. Objectives: The purpose of this study was to expand on our previous work and obtain a snapshot in time of global attitudes towards NPD among practicing functional neurosurgeons. We measure general and regional trends in functional neurosurgery and focus specifically on surgery for mind and mood, while exploring the future prospects of the field. Methods: We designed an online survey and distributed it electronically to 881 members of the following international organizations: World Society for Stereotactic and Functional Neurosurgery, European Society for Stereotactic and Functional Neurosurgery, Asian-Australasian Society for Stereotactic Functional Neurosurgery and the South and Latin American Society for Stereotactic and Functional Neurosurgery. Subsequent statistical and thematic analysis was performed on the data obtained. Results: Of 881 surveys distributed, 106 were returned (12.8%). Eighty-two percent of functional neurosurgeon respondents were fellowship trained, with movement disorders and pain making up the majority of their practice. Psychiatric indications are the most frequently treated conditions for 34% of survey respondents, and over half of participants (51%) perform epilepsy surgery. Of the psychiatric conditions, obsessive-compulsive disorder and depression are the most common disorders treated. The majority of respondents (90%) felt optimistic about the future of NPD. Two thirds cited the reluctance of psychiatrists to refer patients as the greatest obstacle facing the field, and a majority reported that a cultural stigma surrounding psychiatric diseases exists in their community. In response to hypothetical situations involving cognitive and personality enhancement, opinions varied, but the majority opposed enhancement interventions. Regional variations were examined as well and uncovered distinct attitudinal differences depending on geographic location. Conclusions: Surgery for psychiatric conditions is an expanding field within functional neurosurgery. The opinions of international functional neurosurgeons were largely in line with those of their North American colleagues. Optimism regarding the future of NPD predominates, and future editions of this survey can be used to track the evolution of neurosurgeons' attitudes towards NPD and neuroenhancement.
Evaluation of aquaporin‐4 antibody assays

Aquaporin‐4 (AQP4) is a water channel protein that is most highly, but not exclusively, expressed in the central nervous system. In 2005 AQP4 was shown to be the antigenic target of neuromyelitis optica‐immunoglobulin G (NMO‐IgG, or AQP4‐IgG), an antibody found specifically in patients with NMO and in formes frustes of NMO, such as longitudinally extensive transverse myelitis (LETM) or optic neuritis (ON). This discovery facilitated the clinical, pathological, and radiological distinction of NMO and the spectrum of NMO‐related disorders from classical multiple sclerosis. In addition to its use as a diagnostic tool, AQP4‐IgG predicts a high risk of relapse in patients with a clinically isolated syndrome of either LETM or ON. As disability in NMO is attack‐related, early diagnosis and treatment are predicted to have a major effect on long‐term disability. Thus, the importance of sensitive and specific assays to detect AQP4‐IgG cannot be overstated. Both academic institutions and commercial companies have developed assays to identify AQP4‐IgG in patients' sera or cerebrospinal fluid. Both AQP4 isoforms from different species have been used as the antigenic target in the form of frozen tissue sections in indirect immunofluorescence assays, partially purified protein for fluorescence immunoprecipitation assay, radioimmunoprecipitation assay or enzyme‐linked immunosorbent assay, or transfected into cells for cell based assays or flow cytometry. We carried out a systematic review of the literature reporting different methodologies used to identify AQP4‐IgG, examine whether longitudinal AQP4‐IgG titers predict relapses in seropositive patients, and attempt to establish a reasonable timeframe for retesting negative serum samples.
Doppler study of the uterine artery in patients using an intrauterine contraceptive device

A Doppler flow study of the uterine artery was performed using transvaginal sonography in 68 women, including 44 using an intrauterine contraceptive device (IUCD) and 24 control women who were not using any method of contraception. Both the pulsatility index (PI) and resistance index (RI) were significantly lower in women with IUCD‐induced bleeding than in those without abnormal vaginal bleeding (p < 0.001) or in women not using any method of contraception (p < 0.001). No significant variations in PI and RI levels (p > 0.05) were found with the duration of IUCD application or the duration of IUCD‐induced bleeding in patients using the device. Also, no significant changes in blood flow indices were demonstrated between women using the device without abnormal vaginal bleeding and the control group. These preliminary results suggest that some women are more prone to develop IUCD‐induced bleeding than others, and this bleeding may be due to decreased vascular resistance in the uterine artery. Transvaginal Doppler study of the uterine artery may be a helpful technique to identify such women. Copyright © 1994 International Society of Ultrasound in Obstetrics and Gynecology
Serum leptin levels during pregnancy in multiple sclerosis

Background Disease activity in patients with multiple sclerosis (MS) is suppressed during pregnancy, whereas attack frequency increases after delivery. It is yet unclear, which immuno – endocrinological processes mediate these disease fluctuations. Leptin has been identified as a hormone that can influence inflammatory activity. Objective The aim of this study was to investigate whether pregnancy-induced fluctuations of serum leptin levels differed between patients with MS and controls and whether serum leptin levels correlate with periods of enhanced and diminished disease activity. Methods Women with MS and healthy women were prospectively followed during and after pregnancy. The MS group could be studied already at a timepoint before pregnancy. Serum leptin and soluble leptin receptor (SLR) levels were measured using enzyme-linked immunosorbent assay. Results Pre-pregnancy serum leptin levels were (mean ± SD) 22.9 ± 12.8 ng/ml in the MS group. These levels increased in the third trimester to 28.5 ± 15.0 ng/ml (P = 0.007). The third trimester serum leptin levels in healthy women were comparable, 29.4 ± 19.0 ng/ml. Serum leptin levels after delivery dropped to 18.5 ± 12.8 ng/ml in women with MS (P < 0.001) and to a lesser extend (22.0 ± 17.5 ng/ml) in healthy women (P = 0.04). SLR levels showed the same pattern. Remarkably, women with the highest relative decrease in serum leptin levels after delivery had more often a postpartum relapse (P = 0.008). Conclusion In women with MS, leptin increased during late pregnancy. A postdelivery drop in leptin levels was observed in both the MS and control group. The postdelivery drop was associated with the occurrence of postpartum relapse.
Profinite rigidity and surface bundles over the circle

If M is a compact 3‐manifold whose first betti number is 1, and N is a compact 3‐manifold such that π1N and π1M have the same finite quotients, then M fibres over the circle if and only if N does. We prove that groups of the form F2⋊Z are distinguished from one another by their profinite completions. Thus, regardless of betti number, if M and N are punctured‐torus bundles over the circle and M is not homeomorphic to N , then there is a finite group G such that one of π1M and π1N maps onto G and the other does not.
Ultra-Wideband Low-Loss Switch Design in High-Resistivity Trap-Rich SOI With Enhanced Channel Mobility

In this paper, the stress memorization technique (SMT) effects upon ultra-wideband RF switch performance are investigated for the first time. Low insertion loss (IL), high isolation, ultra-wideband (dc to 50 GHz) single-pole double-throw (SPDT), and single-pole four-throw (SP4T) switches designed with commercial 0.13-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> high-resistivity (HR) trap-rich SOI technology with/without SMT are presented and investigated. 2.5 V nMOS transistor (<inline-formula> <tex-math notation="LaTeX">$L_{g} = 0.2~\mu \text{m}$ </tex-math></inline-formula>) with low <inline-formula> <tex-math notation="LaTeX">$R_{\mathrm{\scriptscriptstyle ON}} {^\ast} C_{\mathrm{\scriptscriptstyle OFF}}$ </tex-math></inline-formula> from GF 130RFSOI PDK is used. It is found that channel mobility of switch transistor is improved by SMT and thus switch performance can be further improved. Moreover, the impact of transistor channel length, which has dominant effects on both IL and isolation of the switches, under different gate bias on switch performance are also studied and verified experimentally. Low measured IL of less than 2.1 dB and good isolation of better than 27 dB from dc to 50 GHz are obtained for the SPDT switch. For SP4T switch, the measured IL of less than 2.6 dB and isolation of better than 27 dB are achieved from dc to 35 GHz. The active chip areas of designed SPDT and SP4T switches are compact with size of only <inline-formula> <tex-math notation="LaTeX">$0.214 \times 0.19~\text {mm}^{2}$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$0.36 \times 0.19~ \text {mm}^{2}$ </tex-math></inline-formula>, respectively.
Chimeric subgroup A respiratory syncytial virus with the glycoproteins substituted by those of subgroup B and RSV without the M2-2 gene are attenuated in African green monkeys.

Using the existing reverse genetics system developed for the subgroup A respiratory syncytial virus (RSV), a chimeric virus (designated rA-G(B)F(B)) that expresses subgroup B-specific antigens was constructed by replacing the G and F genes of the A2 strain with those of the 9320 strain of subgroup B RSV. rA-G(B)F(B) grew well in tissue culture, but it was attenuated in the respiratory tracts of cotton rats and African green monkeys. To further attenuate this chimeric RSV, the M2-2 open reading frame was removed from rA-G(B)F(B). rA-G(B)F(B)DeltaM2-2 was highly attenuated in replication in the respiratory tracts of the infected monkeys, but it provided complete protection against wild-type subgroup B RSV challenge following two doses of infection. In this study, rA2DeltaM2-2 (a recombinant A2 RSV that lacks the M2-2 gene) was also evaluated in African green monkeys. The replication of rA2DeltaM2-2 was highly restricted in both the upper and lower respiratory tracts of the infected monkeys and it induced titers of serum anti-RSV neutralizing antibody that were slightly lower than those induced by wild-type rA2. When rA2DeltaM2-2-infected monkeys were challenged with wild-type A2 virus, the replication of the challenge virus was reduced by approximately 100-fold in the upper respiratory tract and 45,000-fold in the lower respiratory tracts. rA2DeltaM2-2 and rA-G(B)F(B)DeltaM2-2 could represent a bivalent RSV vaccine composition for protection against multiple strains from the two RSV subgroups.
Judgement criteria for molar incisor hypomineralisation (MIH) in epidemiologic studies: a summary of the European meeting on MIH held in Athens, 2003.

AIM This paper reviews the proceedings and conclusions of a meeting of experts concerned with the problem of hypomineralised incisors and molars (MIH). The aims of this meeting were to establish criteria for the judgement of MIH, to select representative cases and to discuss how the name of the condition was best described as hypomineralised, or hypomaturated, first permanent molars. CONCLUSION There was not complete agreement as to the correct diagnosis and aetiology of the condition. A suggested list of definitions of the judgement criteria to be used in diagnosing Molar Incisor Hypomineralisation (MIH) for prevalence studies was agreed upon.
Sustained-release naltrexone for alcoholism treatment: a preliminary study.

UNLABELLED This 12-week study examined the bioavailability, tolerability, and potential efficacy of an injectable sustained-release preparation (SRP) of naltrexone (NTX). Twenty alcohol-dependent subjects took NTX 50 mg po daily for 2 weeks, followed by a 2-week, no-medication Washout Period, a 4-week Injection Period, and a 4-week Follow-up Period. Fifteen subjects (75%) received a single subcutaneous injection of 206 mg of sustained-release NTX, and five subjects (25%) received a placebo injection. All subjects also received eight weekly coping skills sessions during the Oral NTX, and the Washout and Injection Periods. RESULTS After injection, NTX plasma concentrations exceeded a mean of 1 ng/ml for 21 days. Adverse effects produced by the SRP of NTX were comparable with those resulting from oral NTX therapy. Compared with placebo, the SRP of NTX significantly reduced the frequency of heavy drinking days during the Injection and Follow-up Periods. CONCLUSIONS The results of this preliminary study support the potential clinical utility of the SRP of NTX for treatment of alcohol dependence.
CYBB, an NADPH‐oxidase gene: restricted diversity in humans and evidence for differential long‐term purifying selection on transmembrane and cytosolic domains

CYBB encodes the gp91‐phox protein of the phagocytic NADPH oxidase; the innate immunity‐related enzymatic complex responsible for the respiratory burst. Mutations in CYBB can cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by ineffective microbicidal activity, for which over 150 family‐specific mutations have been described. It is also plausible that common SNPs in CYBB alter the expression or function of gp91‐phox, determining differences in susceptibility to complex disorders such as autoimmune or infectious diseases. We have resequenced the exons, UTRs, and intronic regions of CYBB in 102 ethnically diverse individuals and genotyped nine tag‐SNPs in 942 individuals from 52 worldwide populations. The 28 observed SNPs (none of which nonsynonymous) reside on 28 haplotypes that can be collapsed into five clades. CYBB shows lower diversity than other X‐chromosome genes and most of the between‐population genetic variance was observed among Africans and non‐Africans. The African population shows the highest diversity and the lowest linkage disequilibrium (LD). Because there is extensive shared LD among non‐Africans, tag‐SNPs can be effectively employed in gene‐centric association studies and are portable across Eurasian and Native American populations. Comparison of CYBB coding sequences among mammals evidences the action of long‐term purifying selection, which is stronger on the C‐terminal cytosolic domain than on the N‐terminal transmembrane domain of gp91‐phox. Hum Mutat 29(5), 623–632, 2008. Published 2008 Wiley‐Liss, Inc.
The effect of exogenous oestrogen on nitric oxide production in women: a placebo controlled crossover study

Nitric oxide is produced from L-arginine and is oxidised rapidly into nitrite and nitrate in vivo. The physiological roles of nitric oxide include vasodilatation, regulation of platelet aggregation, neurotransmission and modulation of host defences (Moncada et al. 1991). There is a growing body of evidence linking the L-arginine nitric oxide pathway to the sex steroid oestrogen. These data are limited to animal studies at present due to the difficulty of obtaining direct measures of nitric oxide production in vivo. It is well known that oestrogen induces vasodilatation (Magness & Rosenfield 1989). This effect may be partially mediated by nitric oxide since the increase in uterine artery blood flow produced by oestrogen in sheep can be reduced by 60 % by administration of N-monomethylarginine (L-NMMA), a specific inhibitor of nitric oxide (Van Buren et a/. 1992). Human uterine artery blood flow, assessed using Doppler ultrasound, can be increased by administration of nitric oxide donor drugs (Ramsay et af. 1994) and also is increased in association with high oestrogen levels during the menstrual cycle (Goswamy & Steptoe 1988), which suggests that the vasodilatory effect of oestrogen in humans may be mediated through nitric oxide. In addition, work with isolated aortic ring preparations has shown gender differences in responses to vasoconstrictors (Zhang et a/. 1992), as well as in basal nitric oxide production (Hayashi et al. 1992). Oestrogens therefore appear to alter vascular smooth muscle tone, an effect which may be partially mediated by nitric oxide. The aim of this study was to investigate the
Opinion Versus Knowledge: The Influence of Testimony Format on Children’s Judgments in Morally Relevant Contexts

ABSTRACT Research Findings: To test children’s use of testimony of others, 3 – 9 years (N = 227) made judgments about a potential peer transgression in which the intentions of the protagonist were ambiguous, after hearing two different forms of testimony. The 2 forms of testimony were (a) opposing opinion-based testimony from an adult authority versus a peer consensus group and (b) knowledge-based testimony (eyewitness testimony) that was counter to the participants’ initial judgments. Findings revealed that when testimony was presented in an opinion-based format, children were likely to side with the opinion that reflected their own interpretation of the peer encounter, regardless of whether the opinion came from a peer consensus or an adult authority. However, when knowledge-based testimony was introduced in support of the opposite of children’s initial interpretation of the ambiguous peer encounter, children most often changed their initial judgment to align with the new testimony. That is, children used knowledge-based testimony but not opinion-based testimony to evaluate a potential transgression. Practice or Policy: These findings demonstrate that the way in which testimony is delivered to children has a direct influence on their decision making about peer interactions and has relevance for teacher–student discourse in the classroom.
Valley polarized relaxation and upconversion luminescence from Tamm-plasmon trion–polaritons with a MoSe2 monolayer

Transition metal dichalcogenides represent an ideal testbed to study excitonic effects, spin-related phenomena and fundamental light-matter coupling in nanoscopic condensed matter systems. In particular, the valley degree of freedom, which is unique to such direct band gap monolayers with broken inversion symmetry, adds fundamental interest in these materials. Here, we implement a Tamm-plasmon structure with an embedded MoSe2 monolayer and study the formation of polaritonic quasi-particles. Strong coupling conditions between the Tamm-mode and the trion resonance of MoSe2 are established, yielding bright luminescence from the polaritonic ground state under non-resonant optical excitation. We demonstrate, that tailoring the electrodynamic environment of the monolayer results in a significantly increased valley polarization. This enhancement can be related to change in recombination dynamics shown in time-resolved photoluminescence measurements. We furthermore observe strong upconversion luminescence from resonantly excited polariton states in the lower polariton branch. This upconverted polariton luminescence is shown to preserve the valley polarization of the trion–polariton, which paves the way towards combining spin-valley physics and exciton scattering experiments.
Spatio-temporal Analysis of Molecular Determinants of Neuronal Degeneration in the Aging Mouse Cerebellum*

The accumulation of cellular damage, including DNA damage, is hypothesized to contribute to aging-related neurodegenerative changes. DNA excision repair cross-complementing group 1 (Ercc1) knock-out mice represent an accepted model of neuronal aging, showing gradual neurodegenerative changes, including loss of synaptic contacts and cell body shrinkage. Here, we used the Purkinje cell-specific Ercc1 DNA-repair knock-out mouse model to study aging in the mouse cerebellum. We performed an in-depth quantitative proteomics analysis, using stable isotope dimethyl labeling, to decipher changes in protein expression between the early (8 weeks), intermediate (16 weeks), and late (26 weeks) stages of the phenotypically aging Ercc1 knock-out and healthy littermate control mice. The expression of over 5,200 proteins from the cerebellum was compared quantitatively, whereby 79 proteins (i.e. 1.5%) were found to be substantially regulated during aging. Nearly all of these molecular markers of the early aging onset belonged to a strongly interconnected network involved in excitatory synaptic signaling. Using immunohistological staining, we obtained temporal and spatial profiles of these markers confirming not only the proteomics data but in addition revealed how the change in protein expression correlates to synaptic changes in the cerebellum. In summary, this study provides a highly comprehensive spatial and temporal view of the dynamic changes in the cerebellum and Purkinje cell signaling in particular, indicating that synapse signaling is one of the first processes to be affected in this premature aging model, leading to neuron morphological changes, neuron degeneration, inflammation, and ultimately behavior disorders.