Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutting Edge: Small Molecule CD40 Ligand Mimetics Promote Control of Parasitemia and Enhance T Cells Producing IFN-γ during Experimental Trypanosoma cruzi Infection1

Host resistance to Trypanosoma cruzi infection depends on a type 1 response characterized by a strong production of IL-12 and IFN-γ. Amplifying this response through CD40 triggering results in control of parasitemia. Two newly synthesized molecules (<3 kDa) mimicking trimeric CD40L (mini CD40Ls-1 and -2) bind to CD40, activate murine dendritic cells, and elicit IL-12 production. Wild-type but not CD40 knockout mice exhibited a sharp decrease of parasitemia and mortality when inoculated with T. cruzi mixed with miniCD40Ls. Moreover, the immunosuppression induced by T. cruzi infection was impaired in mice treated with miniCD40Ls, as shown by proliferation of splenic lymphocytes, percentage of CD8+ T cells, and IFN-γ production. Mice surviving T. cruzi infection in the presence of miniCD40L-1 were immunized against a challenge infection. Our results indicate that CD40L mimetics are effective in vivo and promote the control of T. cruzi infection by overcoming the immunosuppression usually induced by the parasites.
Biochemical characterization and analysis of the transforming potential of the FLT3/FLK2 receptor tyrosine kinase.

We recently cloned an additional member of the receptor type tyrosine kinase class III. This new gene, called Flt3 by our group [Rosnet, O. , Matteï, M.G. , Marchetto, S. & Birnbaum, D. (1991). Genomics, 9, 380-385; Rosnet, O. , Marchetto, S. , deLapeyriere, O. & Birnbaum, D. (1991). Oncogene, 6, 1641-1650] and Flk2 by others [Matthews, W. , Jordan, C.T. , Wieg, G.W. , Pardoll, D. & Lemischka, I.R. (1991). Cell, 65, 1143-1152] is strongly related to the important developmental genes Kit, Fms and Pdgfr. The murine 3.2-kb full-length cDNA, when introduced into COS-1 cells, shows the expression of two polypeptides with apparent molecular weights of 155 kDa and 132 kDa. Treatment of cells with N-linked glycosylation inhibitors results in the expression of a 110-kDa protein. We have shown that FLT3 contains an intrinsic tyrosine kinase activity. A point mutation in a highly conserved residue within the phosphoryltransferase domain inactivates the catalytic function of this receptor, whereas activation by way of a chimeric molecule between the ligand-binding domain of colony-stimulating factor type 1 (CSF-1) receptor (CSF-1R) and the kinase domain of FLT3 results, in the presence of CSF-1, in the development of the transforming activity of this receptor as shown by anchorage-independent cell growth. Finally, expression analysis of the FLT3 protein shows that, in addition to the hematopoietic system, FLT3 is strongly expressed in neural, gonadal, hepatic and placental tissues in the mouse.
Increased estradiol and improved sleep, but not hot flashes, predict enhanced mood during the menopausal transition.

BACKGROUND The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. METHODS Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. RESULTS Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. CONCLUSIONS For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.
Operational characteristics of an IPM-type bearingless motor with 2-pole motor windings and 4-pole suspension windings

A bearingless motor (BelM) integrates the characteristics of an electric motor and a magnetic bearing. Typically, a surface-mounted permanent magnet (SPM)-type BelM with a ring magnet magnetized in parallel is employed for high-speed operation. It is noteworthy that a carbon fiber bandage is needed to fix the ring magnet. However, when an SPM-type BelM is applied to a high-output motor, it becomes difficult to generate sufficient suspension force because of the wide magnetic gap arising from the carbon fiber bandage and the ring magnet. In addition, the manufacturing cost for the large-scale ring magnet and the carbon fiber bandage is high. Therefore, to realize a high-output and high-speed BelM at a low cost, we have focused on an interior permanent magnet (IPM)-type BelM with 2-pole motor windings and 4-pole suspension windings. Moreover, a rotor structure for suppressing suspension force ripple arising in the IPM-type BelM has been proposed based on three-dimensional finite element analysis. In this study, a prototype of the IPM-type BelM with the proposed rotor structure is produced. Experiments with this prototype show that the proposed rotor structure is effective in reducing suspension-force ripple. Additionally, the operational characteristics of the prototype are shown in detail.
Histamine H3‐receptor stimulation is unable to modulate noradrenaline release by the isolated rat heart during ischaemia‐reperfusion

Abstract— The aim of this study was to evaluate the ability of H3‐histaminergic prejunctional receptors to modulate the noradrenaline release induced by myocardial ischaemia in the rat, and the effects of an eventual modulation on haemodynamic, biochemical and electrophysiological parameters. Isolated rat hearts were perfused according to the Langendorff technique. Control hearts (n = 13) were not treated; two groups were treated with the H3‐agonist R‐α‐methyl‐histamine at 0.3 μM (n = 14) and 1 μM (n = 11) and one group, used as positive control, was treated with the selective α2‐agonist Mivazerol at 0.5 μM (n = 14) added to the perfusion medium. Noradrenaline, lactate and transaminase output in the coronary effluent, as well as various haemodynamic and electrophysiological parameters, were measured during global and total ischaemia (30 min) and reperfusion (30 min). α2‐receptor stimulation increased ischaemia‐induced noradrenaline release during reperfusion (195 ± 13 vs. 145 ± 12 pmol·g−1 in control group, P < 0.05). In contrast, R‐α‐methyl‐histamine, at both doses, did not significantly modify these parameters. Both treatments did not affect ischaemia‐ and reperfusion‐induced haemodynamic (decrease in heart rate or in left ventricular developed pressure), biochemical (lactate and GOT release) and electrophysiological (arrhythmias or increase in action potential duration) alterations. Unlike other species, the rat appears to be insensitive to H3‐histaminergic receptor modulation of ischaemia‐induced noradrenaline release, although a modulation can be seen with other prejunctional receptor agonists.
Functional analysis of six novel ORFs on the left arm of Chromosome XII in Saccharomyces cerevisiae reveals two essential genes, one of which is under cell‐cycle control

Six novel Open Reading Frames (ORFs) located on the left arm of chromosome XII (YLL044w, YLL042c, YLL040c, YLL038c, YLL035w and YLL034c) have been analysed using short‐flanking homology (SFH) gene replacement. Sporulation and tetrad analysis showed that YLL035w and YLL034c are essential for cell growth; yll035w spores arrested after two or three cell divisions, while the majority of yll034c spores stopped growth within two cell cycles after germination. Complementation of the yll035w deletion with its cognate clone, and a promoter‐substitution experiment, indicated that the promoter of YLL035w may lie within the adjacent ORF, YLL036c. Transcriptional analysis demonstrated that YLL035w is under cell‐cycle regulation. Bioinformatic analyses produced significant matches between YLL034c and mammalian valosin and many other ATPases. The standard EUROFAN growth tests failed to reveal obvious phenotypes resulting from deletion of any of the four non‐essential ORFs. Replacement cassettes, comprising the kanMX marker flanked by each ORF’s promoter and terminator regions, were cloned into pUG7. All the cognate clones, except for YLL040c, were generated using direct PCR products amplified from genomic DNA or using gap‐repair. All clones and strains produced have been deposited in the EUROFAN genetic stock centre (EUROSCARF, Frankfurt). Copyright © 2000 John Wiley & Sons, Ltd.
Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease

CONTEXT: Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may be managed by either respiratory specialists (RS) or general medicine physicians (GMP). While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. AIMS: The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. METHODS: A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP) over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. RESULTS: There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3). GMP managed 84 (41.7%) exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001). There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664) and mortality rates (10.7% vs. 6%, P = 0.292) between both groups of patients. CONCLUSION: Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians.
An Anchor-Based Pedestrian Navigation Approach Using Only Inertial Sensors

In inertial-based pedestrian navigation, anchors can effectively compensate the positioning errors originating from deviations of Inertial Measurement Units (IMUs), by putting constraints on pedestrians’ motions. However, these anchors often need to be deployed beforehand, which can greatly increase system complexity, rendering it unsuitable for emergency response missions. In this paper, we propose an anchor-based pedestrian navigation approach without any additional sensors. The anchors are defined as the intersection points of perpendicular corridors and are considered characteristics of building structures. In contrast to these real anchors, virtual anchors are extracted from the pedestrian’s trajectory and are considered as observations of real anchors, which can accordingly be regarded as inferred building structure characteristics. Then a Rao-Blackwellized particle filter (RBPF) is used to solve the joint estimation of positions (trajectory) and maps (anchors) problem. Compared with other building structure-based methods, our method has two advantages. The assumption on building structure is minimum and valid in most cases. Even if the assumption does not stand, the method will not lead to positioning failure. Several real-scenario experiments are conducted to validate the effectiveness and robustness of the proposed method.
Menstruation‐related spontaneous pneumothorax and diaphragmatic endometriosis

Menstruation‐related spontaneous pneumothorax (MSP), also termed catamenial pneumothorax, is a syndrome of spontaneous pneumothorax during menstruation due to endometriotic lesions in the diaphragm and thoracic cavity. Previously MSP was considered rare, and to cause only 3–6% of all spontaneous pneumothoraces in otherwise healthy women. Current data suggest that the incidence is substantially higher and MSP might be the reason for spontaneous pneumothoraces in up to 25–33% of all cases in women of reproductive age. The typical characteristics are a high recurrence rate and diaphragmatic spread of endometriotic lesions. We report six patients who had been diagnosed to have diaphragmatic endometriosis and four of them had developed MSP. Optimal management requires flexible collaboration between thoracic surgeons and gynecologists. Although treatment is primarily surgical, long‐lasting and successful management requires that amenorrhea is induced with hormonal therapy, either by continuous contraceptives, progestins, the levonorgestrel‐releasing intrauterine device or GnRH‐agonists.
Clinical contrast sensitivity chart evaluation

Three different types of contrast sensitivity chart were used on normal patients by six optometrists in clinical practice. The charts were the Vistech, the Pelli ‐Robson and the Cambridge low‐contrast gratings test. We examine the data in terms of the differences between optometrists and the variation of contrast sensitivity with the age of the patient. There was a highly significant difference between the scores from different optometrists for all three charts. We attribute this to variability in measurement technique. There was also a highly significant effect of age for all three charts, with older observers tending to exhibit lower contrast sensitivity. On the Vistech chart, this sensitivity deficit was most pronounced at higher spatial frequencies. The level of redundant information in the tests is discussed.
Epidemiology and statistical methods in prediction of patient outcome

Substantial gaps exist in the data of the assessment of risk and prognosis that limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic, prostate cancer, of our time. This report was prepared by an international multidisciplinary committee of the World Health Organization to address contemporary issues of epidemiology and statistical methods in prostate cancer, including a summary of current risk assessment methods and prognostic factors. Emphasis was placed on the relative merits of each of the statistical methods available. We concluded that: An international committee should be created to guide the assessment and validation of molecular biomarkers. The goal is to achieve more precise identification of those who would benefit from treatment. Prostate cancer is a predictable disease despite its biologic heterogeneity. However, the accuracy of predicting it must be improved. We expect that more precise statistical methods will supplant the current staging system. The simplicity and intuitive ease of using the current staging system must be balanced against the serious compromise in accuracy for the individual patient. The most useful new statistical approaches will integrate molecular biomarkers with existing prognostic factors to predict conditional life expectancy (i.e. the expected remaining years of a patient's life) and take into account all-cause mortality.
Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation

Objective Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone density of the bisphosphonate risedronate in osteopenic Crohn's disease patients. Methods This double-blind, placebo-controlled randomised trial of risedronate with calcium and vitamin D supplementation was performed in osteopenic Crohn's disease patients. Patients were treated for 2 years with follow-up after 3 and after every 6 months. Disease characteristics and activity and bone turnover markers were assessed at all visits; dual x-ray absorptiometry was performed at baseline, 12 and 24 months; radiographs of the spine at baseline and 24 months. Results Of 132 consenting patients, 131 were randomised (67 placebo and 64 risedronate). Patient characteristics were similar in both groups, although the risedronate group was slightly heavier (body mass index 24.3 vs 23.0 kg/m2). Bone mineral density at lumbar spine increased 0.04 g/cm2 on average in the risedronate group versus 0.01 g/cm2 in the placebo group (p=0.007). The mean increase in total hip bone mineral density was 0.03 versus 0.01 g/cm2, respectively (p=0.071). Fracture prevalence and incidence were similar. Change of T-scores and concentrations of bone turnover markers were consistent with a beneficial effect of risedronate when compared with placebo. The effect of risedronate was primarily demonstrated in the first 12 months of treatment. No serious unexpected suspected adverse events were observed. Conclusions A 24-month treatment course with risedronate 35 mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register.
Personality, adrenal steroid hormones, and resilience in maltreated children: A multilevel perspective

In this multilevel investigation, resilience in adaptive functioning among maltreated and nonmaltreated low-income children (N = 677) was examined in relation to the regulation of two stress-responsive adrenal steroid hormones, cortisol and dehydroepiandrosterone (DHEA), as well as the personality constructs of ego resiliency and ego control. Maltreatment status was not related to differences in average levels of morning or afternoon cortisol or DHEA. However, lower morning cortisol was related to higher resilient functioning, but only in nonmaltreated children. In contrast, among physically abused children, high morning cortisol was related to higher resilient functioning. Morning and afternoon DHEA was negatively related to resilient functioning. Although diurnal change in cortisol was not related to resilience, for DHEA, maltreated children with high resilience showed an atypical rise in DHEA from morning to afternoon. Morning and afternoon cortisol/DHEA ratios were positively related to resilient functioning, but did not interact with maltreatment status. Ego resiliency and ego control strongly differentiated maltreated and nonmaltreated children, and the personality variables were substantially predictive of resilience. When considered together, demonstrated effects of personality, cortisol, and DHEA maintained independent contributions in predicting resilience among high-risk youth.
Analysis of the DXD Motifs in Human Xylosyltransferase I Required for Enzyme Activity*

Human xylosyltransferase I (XT-I) is the initial enzyme involved in the biosynthesis of the glycosaminoglycan linker region in proteoglycans. Here, we tested the importance of the DXD motifs at positions 314–316 and 745–747 for enzyme activity and the nucleotide binding capacity of human XT-I. Mutations of the 314DED316 motif did not have any effect on enzyme activity, whereas alterations of the 745DWD747 motif resulted in reduced XT-I activity. Loss of function was observed after exchange of the highly conserved aspartic acid at position 745 with glycine. However, mutation of Asp745 to glutamic acid retained full enzyme activity, indicating the importance of an acidic amino acid at this position. Reduced substrate affinity was observed for mutants D747G (Km = 6.9 μm) and D747E (Km = 4.4 μm) in comparison with the wild-type enzyme (Km = 0.9 μm). Changing the central tryptophan to a neutral, basic, or acidic amino acid resulted in a 6-fold lower Vmax, with Km values comparable with those of the wild-type enzyme. Despite the major effect of the DWD motif on XT-I activity, nucleotide binding was not abolished in the D745G and D747G mutants, as revealed by UDP-bead binding assays. Ki values for inhibition by UDP were determined to be 1.9–24.6 μm for the XT-I mutants. The properties of binding of XT-I to heparin-beads, the Ki constants for noncompetitive inhibition by heparin, and the activation by protamine were not altered by the generated mutations.
WEE2 Is an Oocyte-Specific Meiosis Inhibitor in Rhesus Macaque Monkeys1

WEE1 homolog 2 (WEE2, also known as WEE1B) is a newly identified member of the WEE kinase family that is conserved from yeast to humans. The aim of the present study was to determine the spatiotemporal expression pattern and the function of WEE2 during oocyte maturation in a nonhuman primate species, the rhesus macaque. Among 11 macaque tissues examined, WEE2 transcript is predominantly expressed in the ovary and only weakly detectable in the testis. Within the ovary, WEE2 mRNA is exclusively localized in the oocyte and appears to accumulate during folliculogenesis, reaching the highest level in preovulatory follicles. Microinjection of a full-length WEE2-GFP (green fluorescent protein) fusion mRNA indicates a specific nuclear localization of WEE2 protein in both growing and fully grown germinal vesicle (GV)-intact oocytes. Taking the long double-stranded RNA-mediated RNA interference approach, we found that down-regulation of WEE2 led to meiotic resumption in a subset of GV oocytes even in the presence of a phosphodiesterase 3 inhibitor. On the other hand, overexpression of WEE2 delays the reentry of oocytes into meiosis in both mice and monkeys. These findings suggest that WEE2 is a conserved oocyte-specific meiosis inhibitor that functions downstream of cAMP in nonhuman primates.