Miracle-dz/UniFAR-FTUs huggingface dataset:
Ontogenesis of physiological responsiveness and guanine nucleotide sensitivity of cardiac muscarinic receptors during chick embryonic development.

Atria isolated from 4-day chick embryos were much less responsive to the negative chronotropic effect of muscarinic agonists than were atria from 5- or 8-day embryos, even though the density of muscarinic acetylcholine receptors (mAChR) was similar at all these ages. The mAChR in hearts from 4-day embryos were also significantly less susceptible to regulation of receptor number by in vivo agonist treatment and required a 2-5-fold greater dose of the muscarinic agonist carbachol to achieve a decrease in receptor number equivalent to that observed in 5- or 8-day embryonic hearts. When 4-day atrial membranes were assayed in physiological buffers, agonist binding to the mAChR was not regulated by GTP unless a sulfhydryl reducing agent was present. Receptors from 5- and 8-day embryos did not require addition of a sulfhydryl reducing agent in order to see guanine nucleotide effects on agonist binding. Even in the presence of a sulfhydryl reducing agent, carbachol binding to the mAChR in 4-day membranes was much less sensitive to guanyl-5'-yl imidodiphosphate (GppNHp) than binding to mAChR in 5- or 8-day membranes. In addition, forskolin-activated adenylate cyclase activity was much less sensitive to inhibition by GppNHp in membranes from 4-day atria than from 5- and 8-day atria. The GTP-binding component (NI) which couples the mAChR to inhibition of adenylate cyclase activity was examined by covalent modification with pertussis toxin. (ABSTRACT TRUNCATED AT 250 WORDS)
The origins of glioma: E Pluribus Unum?

Malignant glioma is among of the most devastating, and least curable, types of cancer. Since the re‐emergence of the cancer stem cell hypothesis, much progress has been made towards elucidating the cellular origin of these tumors. The hypothesis that tumors are hierarchically organized, with a cancer stem cell at the top that shares defining features with somatic stem cells and provides therapeutic refractoriness properties, has put adult stem cells into the limelight as prime suspect for malignant glioma. Much confusion still exists, though, as to the particular cell type and processes that lead to oncogenic transformation. In this review, we will discuss recent developments and novel hypotheses regarding the origin of malignant gliomas, especially glioblastoma. In particular, we argue that glioblastoma is the result of different pathways originating in multiple sources that all ultimately converge in the same disease. Further attention is devoted to potential scenarios leading to transformation of different stem/progenitor cell types of the brain, and the probability and relevance of these scenarios for malignant tumorigenesis. © 2011 Wiley‐Liss, Inc.
Indications, results, and complications of tacrolimus conversion in pediatric renal transplantation

Abstract: It is the practice of many pediatric renal transplant programs to ‘convert’ children taking cyclosporin A (CsA) to tacrolimus, although the indications for, outcome, and complications of this practice remain obscure. To better understand these aspects of tacrolimus ‘conversion’, a fax survey was sent to 119 North American pediatric renal transplant centers. Analyzable responses were received from 52 centers (44%), and included data from ≈ 1,815 pediatric renal transplants performed between 1991 and 98. Strong indications for tacrolimus conversion were: antibody‐resistant rejection, CsA‐resistant rejection, and CsA intolerance (strong indication in 72%, 65%, and 52% of centers, respectively). Steroid‐resistant rejection and cosmetic side‐effects were considered strong indications less often. Initial anti‐rejection therapy was usually increased corticosteroid dose (47/52 centers). Antibody therapy was most commonly used for steroid‐resistant rejection (44 centers). For steroid‐ and antibody‐resistant rejection, tacrolimus conversion was most common (33 centers). Tacrolimus conversion for antibody‐resistant rejection led to improvement of serum creatinine (SCr) in 27% of patients, stabilization of SCr in 46%, worsening of SCr in 11%, and graft loss in 16%. Reported complications after tacrolimus conversion included hyperglycemia, hyperkalemia, lymphoproliferative disorder, infection, and neurologic problems. We conclude that the major indication for tacrolimus conversion in pediatric transplant programs appears to be rejection. Outcome after tacrolimus conversion appears good, with the majority of patients experiencing stable or improved allograft function. These data provide direction for further study, including timing of tacrolimus conversion and interaction with other therapies.
Ten year cerebrovascular morbidity and mortality in 68 year old men with asymptomatic carotid stenosis

Abstract Objective: To study the natural course of carotid artery stenosis detected by ultrasonography. Design: Prospective cohort study. Baseline examination in 1982-3 included ultrasound examination of carotid arteries, measurement of anklebrachial blood pressure index, and detection of atrial fibrillation by 24 hour ambulatory electrocardiography. Setting: Malmo, a city in southern Sweden with 230000 inhabitants. Subjects: 470 men aged 68 years randomly selected from the population. Main outcome measures: Incidence of stroke and transient ischaemic attack and all cause mortality during 10 years of follow up in relation to carotid stenosis, leg artery disease (ankle-brachial blood pressure index below 0.9), and atrial fibrillation. Results: Fifty men had a stroke; six of these were haemorrhagic. Another 11 had a transient ischaemic attack. Eighteen of the men with carotid stenosis (21.6 events/1000 person years) and 43 of the men with normal carotid arteries (14.8 events/1000 person years) had a stroke or transient ischaemic attack (P=0.188). Men with atrial fibrillation had an increased rate of cerebrovascular events (36.7/1000 person years (P=0.048). The highest rate was found in men with asymptomatic disease of the leg arteries (38.6/1000 person years) (P<0.001). The increased risk of stroke or transient ischaemic attack in this group remained after multivariate analysis (relative risk 2.0; 95% confidence interval 1.1 to 3.7). Conclusions: In this cohort carotid stenosis was not associated with an increased risk of stroke. Part of this lack of association was explained by the high mortality from ischaemic heart disease in men with severe stenosis. Twenty seven of the 61 cerebrovascular events, however, occurred in men who had normal carotid arteries, normal ankle pressure, and no atrial fibrillation. Key messages Key messages Asymptomatic atherosclerosis in carotid and leg arteries is a common occurrence among elderly people Both conditions were found to be associated with an excess cardiovascular mortality Compared with leg artery disease, asymptomatic carotid stenosis was not found to be associated with an increased risk of stroke Assessment of peripheral atherosclerotic disease by measurement of arm and ankle blood pressure is a useful method for identifying patients with an increased risk of stroke
Efficient Universal Computation by Greedy Molecular Folding

We introduce and study the computational power of Oritatami, a theoretical model to explore greedy molecular folding, by which the molecule begins to fold before waiting the end of its production. This model is inspired by our recent experimental work demonstrating the construction of shapes at the nanoscale by folding an RNA molecule during its transcription from an engineered sequence of synthetic DNA. While predicting the most likely conformation is known to be NP-complete in other models, Oritatami sequences fold optimally in linear time. Although our model uses only a small subset of the mechanisms known to be involved in molecular folding, we show that it is capable of efficient universal computation, implying that any extension of this model will have this property as well. We develop several general design techniques for programming these molecules. Our main result in this direction is an algorithm in time linear in the sequence length, that finds a rule for folding the sequence deterministically into a prescribed set of shapes depending of its environment. This shows the corresponding problem is fixed-parameter tractable although we proved it is NP-complete in the number of possible environments. This algorithm was used effectively to design several key steps of our constructions.
Multicyclic Components in a Random Graph Process

A limit theorem is obtained for the number of components with more than one cycle that are created during the evolution of a random graph process. In particular, it is shown that the probability that the process never contains more than one such component is about 0.87 © 1993 John Wiley & Sons, Inc. © 1993 Wiley Periodicals, Inc.
Surface of human sperm bears three differently charged CD52 forms, two of which remain stably bound to sperm after capacitation

gp20 is a sialoglycoprotein of the human sperm surface with a core peptide homologous to the leukocyte antigen CD52, a GPI‐anchored glycosylated protein which is described by the monoclonal antibody CAMPATH‐1. Comparative analyses, by means of CAMPATH and anti‐gp20, indicated that they describe it in morphologically and functionally different ways, suggesting that the respective epitopes are different but also casting doubt on the immunological identity of the antigen. In the present study, we used immunodepletion to demonstrate that CAMPATH and anti‐gp20 interact with the same antigen, but that anti‐gp20 has a much higher avidity for the antigen than CAMPATH. Anion exchange fractionation analysis of the antigen revealed three differently charged gp20‐CD52 forms, the least charged of which, was largely without a GPI‐anchor. All three forms were associated with freshly ejaculated sperm, whereas capacitated sperm only contained the two GPI‐anchored, more charged forms, which were also the ones found in the prostasome fraction of seminal plasma and in leukocytes. The two charged, GPI‐anchored forms were described as homogeneous by anti‐gp20, since they ran as a singlet; the third form ran as a doublet. When tested for insertion into Jurkat T cells, the medium charged form inserted the most readily and the less charged one could not be inserted at all. Mol. Reprod. Dev. 60: 89–96, 2001. © 2001 Wiley‐Liss, Inc.
Analysis of Extracting Prior BRDF from MODIS BRDF Data

Many previous studies have attempted to extract prior reflectance anisotropy knowledge from the historical MODIS Bidirectional Reflectance Distribution Function (BRDF) product based on land cover or Normalized Difference Vegetation Index (NDVI) data. In this study, the feasibility of the method is discussed based on MODIS data and archetypal BRDFs. The BRDF is simplified into six archetypal BRDFs that represent different reflectance anisotropies. Five-year time series of MODIS BRDF data over three tiles are classified into six BRDF archetype classes according to the Anisotropy Flat indeX (AFX). The percentage of each BRDF archetype class in different land cover classes or every 0.1-NDVI interval is determined. Nadir BRDF-Adjusted Reflectances (NBARs) and NDVIs simulated from different archetypal BRDFs and the same multi-angular observations are compared to MODIS results to study the effectiveness of the method. The results show that one land cover type, or every 0.1-NDVI interval, contains all the potential BRDF shapes and that one BRDF archetypal class makes up no more than 40% of all data. Moreover, the differences between the NBARs and NDVIs simulated from different archetypal BRDFs are insignificant. In terms of the archetypal BRDF method and MODIS BRDF product, this study indicates that the land cover or NDVI is not necessarily related to surface reflectance anisotropy.
Thyroid hormone replacement--one hormone or two?

Extracts of animal thyroid tissue, first used in 1892, contained both thyroxine and triiodothyronine and were the only available treatment for hypothyroidism for some 50 years. Because of concern about their variable potency,1 these extracts have been considered obsolete for some time by all but a few practitioners, who are often thought by their colleagues to be practicing on the fringes of medicine. Treatment with thyroid extract (or synthetic triiodothyronine) also led to high serum concentrations of triiodothyronine, because of its rapid absorption, and some patients had palpitations one to two hours after taking it. Synthetic thyroxine did not have .
Population-based pharmacokinetics of the soluble TNFr etanercept: a clinical study in 43 patients with ankylosing spondylitis compared with post hoc data from patients with rheumatoid arthritis.

OBJECTIVE The purpose of this study was to evaluate the pharmacokinetics of etanercept in patients with ankylosing spondylitis (AS) in a phase 3 study. METHODS Serum etanercept concentrations were analyzed from samples obtained at weeks 4 and 12 from 43 patients with AS (median age: 45 years; median body weight: 75 kg; white/non-white: 40/3; male/female: 34/9) receiving 25 mg subcutaneously twice weekly for 12 weeks. A population pharmacokinetics analysis using NONMEM was conducted to estimate individual etanercept pharmacokinetic parameters. Initially, appropriate base and covariate population pharmacokinetic models were built based on data from 10 prior clinical studies of etanercept administered subcutaneously or intravenously to healthy subjects (n = 53) and to patients with rheumatoid arthritis (RA) (n = 212). The influence of demographic characteristics on the pharmacokinetics of etanercept was thoroughly evaluated. The stability of the final model was evaluated using both internal (bootstrapping) and external (data splitting) validation approaches. Finally, the selected final population covariate model was used to estimate the Bayesian pharmacokinetic parameters for the patients with AS. RESULTS The data from the 10 prior clinical studies were optimally fitted to a 2-compartment linear population covariate model. Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on clearance. Both bootstrapping and data splitting validated the population model. The mean Bayesian-predicted etanercept clearance and steady-state trough concentration were 0.072 l/h and 2,004 ng/ml, respectively. The pharmacokinetic parameters of etanercept in the patients with AS were similar to those observed in the patients with RA. CONCLUSIONS The pharmacokinetics of etanercept in patients with AS were similar to those in patients with RA. The AS disease state does not appear to alter the disposition of etanercept.
Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific genes, surface markers, growth requirements, colonization of the bone marrow, and generation of B lymphocytes in vivo and in vitro

We describe here the development and characterization of the FLS4.1 stromal line derived from 15-day fetal liver of BALB/c embryos and defined culture conditions that efficiently support the cloning and long-term growth of nontransformed B-220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B cells (JH-rearranged genes with both light-chain Ig genes in the germ line state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4, rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c-Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the enhanced proliferative response of fetal liver B-220+ B-cell precursors supported by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda 5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell precursors, indicating that the proteins encoded by either gene are not required for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark transcription of the MB-1 gene as one of the earliest molecular events in commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre-B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes; moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do they have rearranged gamma, delta, or beta T-cell antigen receptor genes.
Endovascular Treatment of Thoracic Aortic Pathology: Lessons Learned

Abstract Introduction : Endovascular repair has emerged as a very important treatment modality in the management of thoracic aortic diseases due to its reduced invasiveness especially in patients at increased risk for open surgery. Aim of this study is to analyze the lessons learned in our experience of thoracic aortic endografting. Material and methods : From June 1999 to January 2006, 145 selected patients (121 men and 24 women with a mean age of 70 ± 9 years) with thoracic aorta disease received endovascular treatment with one of four different commercially produced stent grafts (Cook, Gore, Endomed, Medtronic). Indications for treatment included disease of the descending thoracic aorta in 92 cases, of the aortic arch in 43 cases and of the thoracoabdominal aorta in 10 cases. In 48 patients, an hybrid surgical and endovascular approach was required. Results : Primary technical success was achieved in 137/145 (94.5%) cases. One patient died intraoperatively and seven patients had a type “I a” endoleak. In-hospital complications included perioperative stroke in three patients, acute renal failure in two patients, acute respiratory failure in one. Initial clinical success was obtained in 128/145 patients (88.3%) with a mortality rate of 9/145 (6.2%). At 38 ± 16 months, mid-term clinical success was obtained in 89.5% of the followed patients. Two patients died from fatal aneurysm rupture. One type I endoleak was successfully treated with a rescue endovascular procedure, four cases of type I endoleak resolved completely without any further intervention, no new onset endoleak was discovered. One patient underwent a successful open conversion. Aneurysm expansion was observed in one patient. Conclusion : Endovascular surgery is changing the management of complex aortic disease. Synergy between endovascular and surgical procedures may provide a solution for many challenging clinical problems.
Conservation of Liquid and Solid Quantity by the Chimpanzee

Sarah, an adult "language"-trained chimpanzee, made accurate same-different judgments on quantities of liquid and solid matter and conserved both types of quantity despite a transformation in an irrelevant property (shape). Control tests showed that she judged on the basis of inference rather than perceptual evaluation of the quantities. She failed to make accurate same-different judgments on the basis of number, and she was not tested for conservation of this type of quantity.
Novel complement inhibitor limits severity of experimentally myasthenia gravis

Complement mediated injury of the neuromuscular junction is considered a primary disease mechanism in human myasthenia gravis and animal models of experimentally acquired myasthenia gravis (EAMG). We utilized active and passive models of EAMG to investigate the efficacy of a novel C5 complement inhibitor rEV576, recombinantly produced protein derived from tick saliva, in moderating disease severity.
Reliability and validity of the Older Americans Resources and Services (OARS) social resources scale in six European countries.

OBJECTIVES The purpose of this article is to examine data quality, reliability, and construct validity of the Older Americans Resources and Services social resources scale in six European countries (The Netherlands, Luxembourg, Italy, Austria, the United Kingdom, and Sweden). METHODS A questionnaire was administered through face-to-face interviews in five countries, and postal interview in the sixth, to representative populations of adults aged 50 to 90 living independently (N = 12,478). This article examines missing values and distribution of items in the social resources scale, and consistency of skew and kurtosis across countries. We performed item-total correlations and ran confirmatory factor analyses to test a three-factor model obtained in previous U.S. and Spanish analyses. Cronbach's alpha determined the reliability of the factors. RESULTS We observed a relatively large proportion of missing data for one item (have someone who would help you). All items correlated with a score equal to or greater than 0.20. Although the confirmatory factor analyses generally supported the acceptability of the three-factor structure in the European data, the reliability of two dimensions (dependability and affective) was unacceptably low. DISCUSSION Differences across countries make it unlikely that researchers can develop a single social resources scale that would have item equivalence in multiple countries.
Dichotomy of the T cell response to Leishmania antigens in patients suffering from cutaneous leishmaniasis; absence or scarcity of Th1 activity is associated with severe infections

The T cell response was studied in 25 patients suffering from cutaneous leishmaniasis caused by Leishmania major with severe (n= 10) and mild (n= 15) disease manifestations. Peripheral blood mononuclear cells (PBMC) from the patients were activated by sonicates of Leishmania promastigotes (LMP) and amastigotes (LDA), and the surface protease gp63. The proliferative responses to Leishmania antigens were lower in patients with severe disease than in patients with mild disease (P= 0·01–0·05), and such a difference was not observed in the response to purified protein derivative of tuberculin (PPD) or tetanus toxoid (TT). LMP‐induced interferon‐gamma (IFN‐γ) production was lower in patients with severe than in patients with mild disease (P < 0·05). When the IL‐4 and IFN‐γ responses of each patient were considered, two response patterns were observed in the cultures activated by the Leishmania sonicates. One response pattern was characterized by high production of IFN‐γ without production of IL‐4 (a Th1‐like pattern), the other was characterized by low IFN‐γ levels which in most cases were associated with IL‐4 production (not a Th1‐like pattern). These patterns could not be distinguished when the cells from the same donors were stimulated by TT and PPD. The percentages of patients with a Th1‐like response pattern after stimulation by LMP in patients with severe and mild disease manifestations were 30% and 80%, respectively. This difference was statistically significant (P= 0·034).
Medicinal Chemistry of Nucleoside Phosphonate Prodrugs for Antiviral Therapy

Considerable attention has been focused on the development of phosphonate-containing drugs for application in many therapeutic areas. However, phosphonate diacids are deprotonated at physiological pH and thus phosphonate-containing drugs are not ideal for oral administration, an extremely desirable requisite for the treatment of chronic diseases. To overcome this limitation several prodrug structures of biologically active phosphonate analogues have been developed. The rationale behind the design of such agents is to achieve temporary blockade of the free phosphonic functional group until their systemic absorption and delivery, allowing the release of the active drug only once at the target. In this paper, an overview of acyclic and cyclic nucleoside phosphonate prodrugs, designed as antiviral agents, is presented.