Miracle-dz/UniFAR-FTUs huggingface dataset:
Exercise systolic blood pressure at moderate workload predicts cardiovascular disease and mortality through 35 years of follow-up in healthy, middle-aged men

Abstract Objective: There is an association between exercise systolic blood pressure (SBP) and cardiovascular disease and mortality. The aim of this study was to investigate this association, with 35 years of follow-up. Methods: Through 1972–75, 2014 healthy, middle-aged men underwent thorough medical examination and a bicycle exercise test. 1999 participants completed six minutes at 100 W. SBP was measured manually, both before the test and every two minutes during the test. Highest SBP measured during the first six minutes (SBP100W) was used in further analyses. Results: Participants were divided into quartiles (Q) based on their SBP100W; Q1: 100–160 mm Hg (n = 457), Q2: 165–175 mm Hg (n = 508), Q3: 180–195 mm Hg (n = 545) and Q4: 200–275 mm Hg (n = 489). After 35-years follow-up, there was a significant association between exercise SBP at baseline and cardiovascular disease and mortality. In the multivariate analysis adjusting for resting SBP, age, smoking status, total serum cholesterol and family history of coronary heart disease, as well as physical fitness, there is a 1.39-fold (CI: 1.00–1.93, p = 0.05) increased risk of cardiovascular mortality in Q4 compared to Q1. When not adjusting for physical fitness, there is a 1.29-fold (CI: 1.03–1.61, p = 0.02) increase in risk of cardiovascular disease between Q1 and Q4. Conclusions: The results of this study suggest that the association between exercise SBP at moderate workload and cardiovascular disease and mortality in middle-aged men extends through as long as 35 years and into old ages.
SPATIAL EFFECTS ON THE SEGREGATION OF SOUNDS IN VIRTUAL AUDITORY SPACE

Human listeners can segregate sound sources based on differences in frequency content and timing. In addition, spatial separation has been shown to improve this ability. The work presented here is an attempt to characterise the effect of spatial factors on segregation when other distinguishing factors are either unavailable or unreliable. This is relevant to understanding how the auditory system deals with real environments, and is also relevant to the creation of virtual environments where particular auditory objects may need to be distinguishable from other objects. Experiments using various broadband sound sources (white noise, click trains, spoken words) indicate that the segregation of concurrent stimuli requires specific spatial arrangements that allow the auditory system to exploit binaural differences. Monaural spectral cues, while essential for spatialisation, seem to play little role in segregation under these conditions. However, they may be useful when competing stimuli have distinct temporal structures or do not fully coincide in time.
Comparing carbon isotope composition of bulk wood and holocellulose from Quercus cerris, Fraxinus ornus and Pinus radiata tree rings

Abstract: Tree-ring δ13C is widely employed in ecophysiological studies, because it represents an integrated proxy of the ratio between photosynthesis (A) and stomatal conductance (g), which expresses the intrinsic water use efficiency (iWUE), strongly affected by the environmental conditions experienced by the plant during its life span. Tree-ring δ13C also reflects long term variations of atmospheric CO2 concentration and of its carbon isotope composition, partly due to increasing anthropogenic emissions. Carbon isotope abundances in tree rings can be assessed on bulk wood as well as on wood biochemical components, wich show different δ13C values because of secondary discrimination during biosynthesis. We present the results of a comparison between δ13C values of bulk wood and holocellulose samples obtained from the last three (1999, 2000 and 2001) annual growth rings of two hardwood (Quercus cerris L. and Fraxinus ornus L. and one conifer (Pinus radiata D. Don, species. We found that 13C values differed significantly among tree species, both in the case of holocellulose and bulk wood, but only in the case of P. radiata bulk wood samples tend to provide more negative δ13C values than holocellulose, as reported in the literature. We suggest that, at least for the two hardwood species studied, bulk wood is a suitable material to work with for δ13C assessment, whilst in P. radiata holocellulose could provide a more stable and reliable index, when studying plant ecophysiological responses to changing environmental conditions.
Recombinant human insulin-like growth factor: testing the somatomedin hypothesis in hypophysectomized rats.

The in-vivo biological activity of recombinant methionyl insulin-like growth factor I (met-IGF-I) was demonstrated in hypophysectomized rats by following blood glucose after an i.v. bolus injection of met-IGF-I; a dose-dependent decrease in blood sugar was seen. Membrane transport was studied using the non-metabolizable amino acid alpha-aminoisobutyric acid; stimulation was obtained with the highest dose used (90 micrograms/rat). To test the original somatomedin hypothesis, growth studies were performed in hypophysectomized rats. Two or three doses of met-IGF-I were given with three different administration regimes (i.v. or s.c. infusion, or s.c. injections twice daily) for 6 or 8 days. Little growth-promoting activity was observed, with a significant effect on body weight gain obtained only when met-IGF-I was given continuously at the highest dose used (180 micrograms/day). No effect was seen on the in-vivo uptake of radioactive sulphate into cartilage. Epiphyseal cartilage width increased slightly at the highest dose of met-IGF-I, but only when the hormone was given by infusion. When 180 micrograms met-IGF-I/day were given by injections, a significant effect on longitudinal bone growth was obtained (90 micron above control). The levels of IGF in the serum were not measurably increased after s.c. administration of met-IGF-I, whereas after i.v. infusion, significantly raised levels were obtained at the higher dose rates (3.0 +/- 0.3 and 2.8 +/- 0.1 units/ml). Growth hormone was much more effective than met-IGF-I even at 50-fold lower doses. Priming the animals with 10 mu. bovine GH/day followed by combined infusions of GH and met-IGF-I did not reveal any potentiating effects of met-IGF-I in the presence of GH. We conclude that met-IGF-I is a relatively poor growth-promoting agent when given systemically, and that somatomedins are more likely to act as local growth factors rather than as circulating mediators of the growth-promoting effects of GH.
Using standard primipara method to compare the quality of maternity care in Cairo and London

Summary There is no universally agreed definition of quality of care (QoC). However, we assumed that the QoC in a London teaching hospital is high and could be used as a benchmark QoC with which to compare the practice in Cairo. We aim to highlight differences in the frequency of adverse outcomes attributable to differences in the QoC between two maternity teaching hospitals in Cairo and London, in low risk, standard primiparae (SP) delivered in 1999. In Ain Shams Maternity Hospital in Cairo and St Mary's Maternity Hospital in London, the caesarean section rate was 9.1% and 22.5%, respectively (OR = 0.34, p < 0.0001); the instrumental delivery rate was 4.1% and 26.8%, respectively (OR = 0.12, p < 0.0001), and the induction of labour (IOL) rate was 1.1% and 16.7%, respectively (OR = 0.06, p < 0.0001). Third degree perineal tears occurred in 0.3% and 8.2%, of the vaginal deliveries (OR = 0.14, p = 0.002) and the still birth rate was 0.78% and 0.1%, (OR = 7.96, p < 0.01) in the Cairo and London hospitals, respectively. This is the first time the SP method has been used to compare similar institutions in developed and developing countries. Intervention rates were significantly higher at St Mary's and so was the improved fetal outcome. A trade-off of improved fetal outcomes for more interventions is difficult to establish. Residual differences in case mix and patient preferences may explain some of the results.
Characterization of distinct early assembly units of different intermediate filament proteins.

We have determined the mass-per-length (MPL) composition of distinct early assembly products of recombinant intermediate filament (IF) proteins from the four cytoplasmic sequence homology classes, and compared these values with those of the corresponding mature filaments. After two seconds under standard assembly conditions (i.e. 25 mM Tris-HCl (pH 7.5), 50 mM NaCl, 37 degrees C), vimentin, desmin and the neurofilament triplet protein NF-L aggregated into similar types of "unit-length filaments" (ULFs), whereas cytokeratins (CKs) 8/18 already yielded long IFs at this time point, so the ionic strength had to be reduced. The number of molecules per filament cross-section, as deduced from the MPL values, was lowest for CK8/18, i.e. 16 and 25 at two seconds compared to 16 and 21 at one hour. NF-L exhibited corresponding values of 26 and 30. Vimentin ULFs yielded a pronounced heterogeneity, with major peak values of 32 and 45 at two seconds and 30, 37 and 44 after one hour. Desmin formed filaments of distinctly higher mass with 47 molecules per cross-section, at two seconds and after one hour of assembly. This indicates that individual types of IF proteins generate filaments with distinctly different numbers of molecules per cross-section. Also, the observed significant reduction of apparent filament diameter of ULFs compared to the corresponding mature IFs is the result of a "conservative" radial compaction-type reorganization within the filament, as concluded from the fact that both the immature and mature filaments contain very similar numbers of subunits per cross-section. Moreover, the MPL composition of filaments is strikingly dependent on the assembly conditions employed. For example, vimentin fibers formed in 0.7 mM phosphate (pH 7.5), 2.5 mM MgCl2, yield a significantly increased number of molecules per cross-section (56 and 84) compared to assembly under standard conditions. Temperature also strongly influences assembly: above a certain threshold temperature "pathological" ULFs form that are arrested in this state, indicating that the system is forced into strong but unproductive interactions between subunits. Similar "dead-end" structures were obtained with vimentins mutated to introduce principal alterations in subdomains presumed to be of general structural importance, indicating that these sequence changes led to new modes of intermolecular interactions.
A Pseudo-Elliptical Response Filter at W-Band Fabricated With Thick SU-8 Photo-Resist Technology

The design and experimental validation of a pseudo-elliptical response filter at W-Band is presented. A micromachining technique based on the thick SU-8 photo-resist is used to construct the filter. The optimized structure is specially well-suited for the implementation of filters with transmission zeros by means of micromachining techniques, since the extracted poles are implemented by simple stubs without irises. Furthermore, a novel topology based on the use of only three SU-8 layers is presented. This new topology, which includes a novel optimized input/output routing, can be potentially used for the design of high-performance devices with a fast and low-cost production. A fourth-order filter with two transmission zeros has been fabricated (bandwidth 5%), presenting 1.2 dB of insertion loss. This level of loss is equivalent to the actual state-of-art for micromachined filters at W-band, in spite of the reduced height and the split block in the H-plane used in the presented design.
Regulation of 17,20 Lyase Activity by Cytochrome b5 and by Serine Phosphorylation of P450c17*

Cytochrome P450c17 catalyzes the 17α-hydroxylase activity required for glucocorticoid synthesis and the 17,20 lyase activity required for sex steroid synthesis. Most P450 enzymes have fixed ratios of their various activities, but the ratio of these two activities of P450c17 is regulated post-translationally. We have shown that serine phosphorylation of P450c17 and the allosteric action of cytochrome b5 increase 17,20 lyase activity, but it has not been apparent whether these two post-translational mechanisms interact. Using purified enzyme systems, we now show that the actions of cytochrome b5 are independent of the state of P450c17 phosphorylation. Suppressing cytochrome b5 expression in human adrenal NCI-H295A cells by >85% with RNA interference had no effect on 17α-hydroxylase activity but reduced 17,20 lyase activity by 30%. Increasing P450c17 phosphorylation could compensate for this reduced activity. When expressed in bacteria, human P450c17 required either cytochrome b5 or phosphorylation for 17,20 lyase activity. The combination of cytochrome b5 and phosphorylation was not additive. Cytochrome b5 and phosphorylation enhance 17,20 lyase activity independently of each other, probably by increasing the interaction between P450c17 and NADPH-cytochrome P450 oxidoreductase.
The Caenorhabditis elegans Nuclear Receptor Gene nhr-25 Regulates Epidermal Cell Development

ABSTRACT The development of the epidermis of Caenorhabditis elegans involves cell fusion, migration, and differentiation events. To understand the mechanisms underlying these processes, we characterized the roles of NHR-25, a member of the nuclear receptor family of transcription factors. The NHR-25 homologs Ftz-F1 in Drosophila and SF-1 in mammals are involved in various biological processes, including regulation of patterning during development, reproduction, metabolism, metamorphosis, and homeostasis. Impairment of nhr-25 activity leads to severe phenotypes in embryos and many postembryonic tissues. Further analysis has indicated that nhr-25 activity is required for the proper development, including cell-cell fusion, of several epidermal cell types, such as the epidermal syncytial, seam, and Pn.p cells. Our results also suggest that nhr-25 is likely to regulate cell-cell junctions and/or fusion. In a subset of Pn.p cells, called vulval precursor cells, nhr-25 acts collaboratively with the lin-39 Hox gene in regulating vulval cell differentiation. Additionally, our data suggest that nhr-25 may also function with another Hox gene, nob-1, during embryogenesis. Overall, our results indicate that nhr-25 plays an integral role in regulating cellular processes of epidermal cells.
Coping strategies, depression, and anxiety among Ontario family medicine residents.

OBJECTIVE To assess the current prevalence of depression and anxiety among Ontario family medicine residents, and to describe their coping strategies. DESIGN Surveys mailed to residents integrated DSM-IV diagnostic criteria and a previously validated Patient Health Questionnaire. SETTING Ontario family medicine programs from June to August 2002. PARTICIPANTS Residents entering, advancing in, or graduating from residency programs: approximately 216 yearly for a total of 649 residents. MAIN OUTCOME MEASURES Types and frequency of coping skills used by residents; prevalence of depressive and anxiety disorders. RESULTS Response rate for residents entering programs was 46% and for graduating residents was 30% (37% response rate overall). Prevalence of depressive disorders was 20% (13% major depressive disorders, 7% other depressive syndromes)(odds ratio [OR] 3.4, confidence interval [CI] 2.7 to 7.5, P < .001). Prevalence of generalized anxiety disorder was 12%, and 2% of residents met criteria for panic syndrome (OR 4.3, CI 1.6 to 11.8, P = .002). Rates were similar for men and women. Medical training was commonly identified as a negative influence on the mental health of troubled residents. Residents most often turned to family and friends when they needed help (43.7% of respondents). About 17.3% saw their family doctors, 15.4% counselors, and 7.9% psychiatrists. Some residents (13.4%) used medication to deal with their affective symptoms, 7.1% underwent cognitive-behavioural therapy, and 8.3% required a leave of absence from their programs. More than half (61.8%) indicated recreational use of alcohol and drugs, 1.2% identified use due to addiction, and 5.9% used drugs to help cope with their problems. Four respondents admitted concern that they might commit suicide during residency; a different three had made previous attempts. CONCLUSION Affective disorders (both depression and anxiety syndromes) are three to four times more common among Ontario family practice residents than in the general population; male and female residents are equally affected. Most residents with these problems report negative effects on their function at work. Medical training is the most commonly identified negative influence on mental health. While residents most often obtain help from family members and friends, many seek professional help.
Contemporary prediction of preeclampsia

Purpose of review To provide a concise review of advances in prediction of preeclampsia, highlighting the most important and interesting articles among the many published within the past months, making a clear distinction between early and late clinical forms of the condition. Recent findings The performance of maternal levels of angiogenic factors to predict preeclampsia, especially early-onset preeclampsia, could be further improved by combining several markers and by evaluating the longitudinal changes between the first and second trimester. Combining first trimester angiogenic factors with maternal history, mean blood pressure and uterine artery Doppler achieves a detection rate of approximately 90% for an approximately 10% of false positives for early preeclampsia. The incorporation of parameters reflecting maternal vascular stiffness into multiparametric models in contingent strategies might result in fewer tests than concurrent screening, with similar prediction performance. Summary Combining several tests into multiparametric models results in the early identification of the vast majority of cases bound to develop early preeclampsia, which is the clinical form that most contributes to adverse maternal and perinatal outcome. This may allow more efficient allocation of resources according to the individual risk and the evaluation of prophylactic strategies in a selected subgroup of women.
Transmission disequilibrium analysis of the functional 5-HT3A receptor variant C178T in early-onset obsessive—compulsive disorder

The 5-HT3 receptor is unique among the serotonin receptors in that it is a ligand-gated ion channel. Dysfunction of the serotonin system is thought to contribute to the pathogenesis of obsessive—compulsive disorder (OCD). Apart from the standard treatment with serotonin reuptake inhibitors and behavioural therapy, a 5-HT3 receptor antagonist has recently been shown to benefit some OCD patients, suggesting the 5-HT3 receptor as a serotonergic candidate gene in the polygenic aetiology of OCD. A functional regulatory variant of the 5-HT3A receptor influences 5-HT 3 receptor expression, serotonin metabolites in cerebrospinal fluid, and amygdala reactivity. We therefore assessed whether this C178T variant influences the risk of developing OCD. In a family-based approach employing the transmission disequilibrium test, we analysed a unique sample of 75 children and adolescents with OCD, as well as their biological parents. We found no evidence for a preferential transmission of either allele to the patients — the estimated transmission rate for the C allele was 0.51 (95% CI 0.36—0.65). This argues against an involvement of the 5-HT3A receptor in the polygenic aetiology of early-onset OCD.
Reduced Pathology following Infection with Transgenic Leishmania major Expressing Murine CD40 Ligand

ABSTRACT Leishmanization is the inoculation of live Leishmania into the host to vaccinate against subsequent infections. This approach has been largely discontinued due to safety concerns. We have previously shown that combining CD40 ligand (CD40L) with Leishmania antigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G. Chen, P. A. Darrah, and D. M. Mosser, Infect. Immun. 69:3255-3263, 2001). In the present study, we developed transgenic L. major organisms which express and secrete the extracellular portion of CD40L (L. major CD40LE). We hypothesized that these organisms would be less virulent but more immunogenic than wild-type organisms and therefore be more effective at leishmanization. Transgenic parasites expressing CD40L mRNA and protein were developed. BALB/c mice infected with these parasites developed significantly smaller lesions containing fewer parasites than animals infected with wild-type organisms. Infection of resistant C57BL/6 mice with low doses of transgenic parasites induced a significant amount of protection against subsequent high-dose infection with wild-type organisms. These results demonstrate that transgenic organisms expressing CD40L are less virulent than wild-type organisms while retaining full immunogenicity.
Nuthatches eavesdrop on variations in heterospecific chickadee mobbing alarm calls

Many animals recognize the alarm calls produced by other species, but the amount of information they glean from these eavesdropped signals is unknown. We previously showed that black-capped chickadees (Poecile atricapillus) have a sophisticated alarm call system in which they encode complex information about the size and risk of potential predators in variations of a single type of mobbing alarm call. Here we show experimentally that red-breasted nuthatches (Sitta canadensis) respond appropriately to subtle variations of these heterospecific “chick-a-dee” alarm calls, thereby evidencing that they have gained important information about potential predators in their environment. This study demonstrates a previously unsuspected level of discrimination in intertaxon eavesdropping.
Physical and Functional Association of Cortactin with Syk in Human Leukemic Cell Line K562 (*)

Human leukemic cell line K562 is induced to differentiate into the megakaryocytic lineage by stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). We demonstrate here that TPA stimulation increases tyrosine phosphorylation of an 80-kDa protein at an early stage of megakaryocytic differentiation and that this 80-kDa protein is identical with cortactin. Since tyrosine kinase Syk was activated by TPA stimulation, we examined the possibility that cortactin is a potential substrate of Syk in K562 cells. TPA-induced tyrosine phosphorylation of cortactin was decreased profoundly by overexpression of dominant-negative Syk. Furthermore, cortactin was associated with Syk even before TPA stimulation. Since cortactin was previously referred as an 80/85-kilodalton pp60 substrate, we examined the association between Src and cortactin, whereas its association could not be detected. These data suggest that Syk phosphorylates cortactin in K562 cells upon TPA treatment.