Miracle-dz/UniFAR-FTUs huggingface dataset:
A distinct splice form ofAPC is highly expressed in neurones but not commonly mutated in neuroepithelial tumours

Editor—The APC tumour suppressor gene contains at least 21 exons, including four exons upstream of exon 1.1 2 Alternative splicing involves at least seven exons, including the first five exons, and creates distinct splice forms of APC RNA.1-4Exon 1 contains an in frame stop codon upstream of its initiating methionine; hence only splice forms of APC that lack exon 1 allow exons 5′ of exon 1 to be translated. Interestingly, splice forms lacking exon 1 are enriched in terminally differentiated tissues including brain,5 intimating that protein isoforms containing domains encoded by the exons 5′ to exon 1 may be important in cellular differentiation. This study evaluates neurones and glia of the rodent nervous system and asks which cell types express APC isoforms lacking exon 1. Medulloblastomas and glioblastomas are neuroepithelial tumours derived from neuronal progenitor cells and glial cells, respectively.6 7 Both tumour types occur at increased frequency in a subset of adenomatous polyposis coli (APC) patients8; APC patients developing these tumour types have a variant of APC known as Turbot's syndrome.9 APC is an autosomal dominant disorder caused by the inactivation of one copy of the APC gene.10 11APC patients develop hundreds to thousands of adenomatous polyps and if the colon is not removed, colon carcinoma develops.8 The relative risk of brain tumour formation is 23 times greater for APC patients when compared to the general population between the ages of 0 and 29.12 This study also examines the genetic basis of neuroepithelial tumour formation and examines APC as a mutational target in medulloblastomas and glioblastomas. We assayed 41 sporadic glioblastomas and medulloblastomas, five cell lines derived from neuroepithelial tumour types, and one medulloblastoma from an APC patient to examine the possibility that mutations in …
Inhibition of Tumor Growth Correlates with the Expression Level of a Human Angiostatin Transgene in Transfected B 16 F 10 Melanoma Cells

Although the therapeutic value of angiostatin, a proteolytic fragment of plasminogen, has been recognized for the treatment of cancer, the production of bioactive angiostatin remains a difficult task. Here we report that expression of a cDNA encoding a secreted, four-kringle human angiostatin inhibited tumor growth of B16F10 melanoma cells in mice but did not suppress tumor cell growth in culture. After transfection and selection, stable expression of the angiostatin cDNA was demonstrated in several B16F10 clones by quantitative mRNA analysis using the Taqman method. Cells that expressed angiostatin at either a low, medium, or high level were injected into C57BL/6 mice. s.c. Growth of B16F10 tumors was diminished by the angiostatin transgene, and the inhibition was directly proportional to the expression level of angiostatin in the transfected cells. However, suppression of s.c. tumor growth was transient, and eventually, tumors emerged with a strongly decreased expression of the transgene. Angiostatin expression also reduced lung metastasis from i.v. -injected B16F10 cells. Our data indicate that a cDNA encoding bioactive human angiostatin is potentially useful for gene therapy of human cancers, but the delivery of the transgene may require repeated dosing to achieve sustained dormancy of primary tumors and cancer metastases.
Localized Model to Segmentally Estimate Miles per Gallon (MPG) for Equipment Engines

In this paper, we built a localized regression model to estimate the miles per gallon (MPG) characteristic for equipment engines based on a serious physical features of this engine. First, we statistically viewed these parameters to build up a basic understanding of the data we collected. Then, with the belief that engines with similar characteristics will perform similarly, we proposed a novel localized model with a novel optimal function based EM algorithm and a novel self-adjusted optimal clustering algorithm to estimate MPG based on the other fully studied engines with similar physical features.
Planning mobile agent architecture for open network environment

This paper describes a planning mobile agent architecture proposed for open network environments such as the Internet. Mobile agents in this architecture have mobile, planning, and meta-level control functionality, and address the locality, variability, and diversity problems to which open network environments are subject. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(12): 58–66, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10112
Activation of muscarinic cholinergic receptors induces MCF-7 cells proliferation and angiogenesis by stimulating nitric oxide synthase activity

Muscarinic acetylcholine receptors (mAChR) are members of the G-protein coupled receptor family. These receptors play key physiological roles and changes in their expression and/or function are involved in several diseases. We had previously demonstrated that mAChR expression is up regulated in three different cell lines derived from distinct murine mammary adenocarcinomas that spontaneously arose in BALB/c female mice, in comparison with normal murine mammary cells. Stimulation of mAChR with the muscarinic agonist carbachol (CARB) potentiated different steps of tumor progression. We here evidence that similarly to previous results obtained in mice, human breast tumor homogenates over expressed mAChR in comparison with normal breast tissue. Thus, to test the muscarinic actions on human breast adenocarcinoma cells we investigate the effect of CARB on MCF-7 cells proliferation and neovascular response. Particularly we observe that: CARB stimulates tumor cells proliferation, being 10-9 M the maximal effective dose for the muscarinic agonist. This action was due to M3 and M1 receptors activation being nitric oxide synthase (NOS) its effector enzyme via phospholipase C and protein kinase C signaling pathway. NOS1 and NOS3 isoforms are expressed in MCF-7 cells and its activation by CARB triggers nitric oxide synthesis and vascular endothelial growth factor expression increasing blood vessels formation induced by mammary tumor cells in vivo. We can conclude that non-neuronal cholinergic system activation stimulates MCF-7 tumor cells growth and neovascular response promoting tumor progression.
Risk identification and interventions to prevent type 2 diabetes in adults at high risk: summary of NICE guidance

Almost three million people in the United Kingdom have diabetes and 850 000 people may be undiagnosed. It has been estimated that five million people will have diabetes by 2025. About 90% of them will have type 2 diabetes.1 About 15% (one in seven) of adults have impaired glucose regulation,2 and an estimated 5-12% of these people develop type 2 diabetes each year.1 People with impaired glucose regulation are 5-15 times more likely to develop type 2 diabetes than those with normal glucose values.3 Successful prevention requires population based action for the whole community,4 together with interventions targeted at those at greatest risk. This article summarises the recommendations from the National Institute for Health and Clinical Excellence (NICE) on the identification and management of type 2 diabetes in people aged 18 or more who are at high risk.5 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When limited evidence is available, recommendations are based on expert testimony and the Programme Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Risk identification: stage 1
The good use of plasma. A critical analysis of five international guidelines.

BACKGROUND The clinical use of fresh-frozen plasma (FFP) is progressively increasing both nationally and internationally, despite the fact that many studies have shown the weaknesses of the indications for its use. Guidelines on the good use of plasma have, therefore, been adopted in various countries. The aim of the present study was to analyse some of the existing guidelines on the good use of plasma, applying a scientifically validated method, as a preliminary step in the implementation of Regional guidelines. METHODS Abibliographic search (1990-2006) was conducted in databases, websites, and the archives of scientific societies. Relevant articles were recovered in full. The selected guidelines were evaluated using theAGREE instrument, which assesses the completeness and structural quality of the guidelines and, in some aspects, the contents of the recommendations. The project, co-ordinated by the Regional Centre for Co-ordination and Compensation (CRCC) and carried out by four Services of Immunohaematology and Transfusion (SIT) in Umbria, was funded by the Region of Umbria and approved by the four health care institutions involved. RESULTS The bibliographic search yielded 3067 abstracts of which 239 were considered relevant. The analysis of these led to the recovery of 11 guidelines, among which five were selected: those from the British Committee for Standards in Haematology, theAgence Française de Securité Sanitaire de Produits de Sante, the Canadian Members of the Expert Working Group, the American Society of Anesthesiologists Task Force on Blood Component Therapy and the National Health and Medical Research Council (NHMRC)/Australasian Society of Blood Transfusion. CONCLUSIONS None of the guidelines analysed obtained a score higher than 50% in all the domains of the AGREE score. There was no evidence of a tendency to improvement over time in the guidelines analysed. Objective evaluation of the guidelines analysed could provide the starting point for the subsequent production of similar documents.
Improvement of the high nonlinear S-boxes generation method

This paper presents improvement of the high nonlinear S-boxes generation method by the appropriate selection of the criteria application order which decreases the required computation power for S-box generation. The proposed modification allows generation of a byte S-box with nonlinearity 104, algebraic immunity 3 and maximum of difference distribution table 8 within approximately 30 minutes of a single PC running time.
When Rivers Become Reservoirs of Antibiotic Resistance: Industrial Effluents and Gene Nurseries

Industrially polluted streams and rivers are of great concern to public health officials and environmental regulators. A lesser known problem is that some water resources have become reservoirs of antibiotic resistance genes that can, under natural conditions, be transferred to water-borne pathogens. The current opinion in the scientific community is that the rapid and continuing increase in antibiotic resistance found in clinical settings is caused by the misuse and overuse of antibiotics in medicine and agriculture. We present here a summary of studies, primarily at the Savannah River Site (South Carolina), that demonstrate that bacteria exposed to heavy metal pollution show elevated levels of antibiotic resistance (AR) and multiple antibiotic resistance (MAR) without ever being directly exposed to antibiotics.
Hyperphosphorylated Tau in an α‐synuclein‐overexpressing transgenic model of Parkinson’s disease

Although clinically distinct diseases, tauopathies and synucleinopathies share a common genesis and mechanisms, leading to overlapping degenerative changes within neurons. In human postmortem striatum of Parkinson’s disease (PD) and PD with dementia, we have recently described elevated levels of tauopathy, indexed as increased hyperphosphorylated Tau (p‐Tau). Here we assessed tauopathy in striatum of a transgenic animal model of PD, overexpressing human α‐synuclein under the platelet‐derived growth factor promoter. At 11 months of age, large and progressive increases in p‐Tau in transgenic mice, hyperphosphorylated at sites reminiscent of Alzheimer’s disease, were noted, along with elevated levels of α‐synuclein and glycogen synthase kinase 3β phosphorylated at Tyr216 (p‐GSK‐3β), a major kinase involved in the hyperphosphorylation of Tau. Differential Triton X‐100 extraction of striata showed the presence of aggregated α‐synuclein in the transgenic mice, along with p‐Tau and p‐GSK‐3β, which was also confirmed through immunohistochemistry. After p‐Tau formation, both Tau and microtubule‐associated protein 1 (MAP1) dissociated from the cytoskeleton, consistent with the diminished ability of these cytoskeleton‐binding proteins to bind microtubules. Increases in free tubulin and actin were also noted, indicative of cytoskeleton remodeling and destabilization. In vivo magnetic resonance imaging of the transgenic animals showed a reduction in brain volume of transgenic mice, indicating substantial atrophy. From immunohistochemical studies, α‐synuclein, p‐Tau and p‐GSK‐3β were found to be overexpressed and co‐localized in large inclusion bodies, reminiscent of Lewy bodies. The elevated state of tauopathy seen in these platelet‐derived growth factor–α‐synuclein mice provides further confirmation that PD may be a tauopathic disease.
Linkage and allelic association of atopy and markers flanking the IL4‐receptor gene

Atopy, a clinical syndrome characterized by heightened IgE responsiveness, is largely determined by genetic factors. The disease may well be heterogeneous but the mode of inheritance is unknown. Several genes have been named which affected IgE responsiveness. However, results are conflicting reflecting heterogeneity and a complicated inheritance pattern of the atopic syndrome. In 1994 linkage of the 5q32 gene region and elevated total IgE levels were reported, leaving the IL4 gene as a prominent candidate.
Comparison of the effects of 6 weeks of squat training with a plyometric training programme upon different physical performance tests in adolescent team handball players

The purpose of this study was to compare the effects of six weeks of squat training with those of plyometric training upon different types of physical performance in adolescent male and female team handball players. Twenty-six adolescent male and female team handball players (age 13.8±0.5 yr, body mass 57.5±11.5 kg, body height 1.70±0.10 m) participated in the study. Half of the subjects (n=13) conducted a squat training program, while the other half conducted a plyometric training program, twice a week for six weeks, in addition to their normal team handball practice. Both groups increased their performance after six weeks in agility, 30 m sprint and Yo-Yo IR1 tests, while no changes were found in the CMJ, strength test and throwing velocity. The results suggest that either a short in-season 6-week squat orplyometric training regimen can improve the physical performance of the lower body, while these programs will not enhance the performance of the upper body.
Selectivity of muscarinic agonists including (+/-)-aceclidine and antimuscarinics on the human intraocular muscles.

The average EC50 value and the maximum response of carbachol on the human circular ciliary muscle obtained within 24 h of postmortem hypoxia was 517 nmol/l and 135 mg, respectively. These values for carbachol did not differ significantly from that of the longitudinal ciliary muscle. However, when tested at 1 mumol/l of carbachol, the peak response of the longitudinal muscle occurred at 59 sec vs 173 sec for that of the circular muscle of 70 year old donors. The relative potency of the muscarinic agonists on the circular muscle was oxotremorine-M, 1 > carbachol, 1/4 > pilocarpine, 1/19 > aceclidine, 1/132. The relative order of potency of agonists was similar for the longitudinal muscle. Only pilocarpine and aceclidine were partial agonists which produced 80-85% of the maximum response. When compared with the EC50 values of aceclidine on the iris sphincter and the longitudinal ciliary muscles, the agonist potency was only 1/28 for the latter tissue. Implications of these findings in relation to the use of these agonists in glaucoma are discussed. The pKB values of muscarinic antagonists on the circular ciliary muscle were: atropine, 8.8; cyclopentolate, 7.8; tropicamide, 7.4; P.F. HHSiD, 7.0; pirenzepine, 6.4; and methoctramine, 5.7. Nearly equal pKB values of each antagonist were obtained for the longitudinal ciliary muscle and iris sphincter. Based on the affinity constants of various competitive antagonists, the human iris as well as ciliary muscles may contain M3, M2 or M4 subtypes of muscarinic receptors.
Fast training Support Vector Machines using parallel sequential minimal optimization

One of the key factors that limit support vector machines (SVMs) application in large sample problems is that the large-scale quadratic programming (QP) that arises from SVMs training cannot be easily solved via standard QP technique. The sequential minimal optimization (SMO) is current one of the major methods for solving SVMs. This method, to a certain extent, can decrease the degree of difficulty of a QP problem through decomposition strategies, however, the high training price for saving memory space must be endured. In this paper, an algorithm in the light of the idea of parallel computing based on Symmetric multiprocessor (SMP) machine is improved. The new technique has great advantage in terms of speediness when applied to problems with large training sets and high dimensional spaces without reducing generalization performance of SVMs.
Z extensions to the RHMAPPER package

MOTIVATION Extensions have been made to the RHMAPPER-1.1 package. One set of extensions computes the totally linked markers and uses the results as input to the salient RHMAPPER functions. The second set of extensions uses TKperl to provide an interactive interface for ease of querying the database and displaying maps. AVAILABILITY The extensions can be obtained via ftp.sanger.ac.uk/pub/zmapper. SUPPLEMENTARY INFORMATION The User's Manual can be viewed from http:/www.sanger.ac.uk/Users/cari/Z.shtml. CONTACT cari@sanger.ac.uk
Transformer Less Power Transfer at Unity Power Factor via HVDC Link Using Improved Power Quality HCC PWM AC-DC Converter

The three-phase bridge topology of the bi-directional boost type improved power quality ac-dc converter (IPQC) is capable of providing power transfer between a high voltage dc (HVDC) link and a relatively low voltage ac system with improved power quality at input ac mains in terms of high power factor and low THD. This paper presents unity power factor operations, in the rectification and inversion modes, with near sinusoidal line currents; of the IPQC that employs IGBTs. The current forced control (CFC) strategy is implemented with closed loop control, adopting the hysteresis-band current control (HCC) pulse width modulation (PWM) technique. Simulation results confirm the efficacy of the control technique.
Di-μ-bromido-tris(triphenylphosphine)-1κP,2κ2 P-disilver(I) tetrahydrofuran 0.85-solvate

In the title binuclear silver(I) complex, [Ag2Br2(C18H15P)3]·0.85C4H8O, the two independent silver(I) ions are briged by two bromide ions. One AgI ion is coordinated by two triphenylphosphine groups with a square-planar geometry, while the second is coordinated by one triphenylphine group with a trigonal-planar geometry. The structure is very similar to that of the dichloromethane solvate reported by Zhu, Huang & Zheng [Chin. J. Struct. Chem. (1994), 13, 325–327]. The tetrahydrofuran solvent molecule is disordered and was refined with a fixed occupancy of 0.85.
The primary cilium at a glance

The primary cilium, which was first so named by Sergei Sorokin ([Sorokin, 1968][1]), is a solitary organelle that emanates from the cell surface of most mammalian cell types during growth arrest. Increasing evidence suggests that primary cilia are key coordinators of signaling pathways during
The Role of Semantics in Improving Medical Doctors’ Performance

In the last years, the use of robotics and semantics inmedical context has become more and more essential to improvemedical doctors' performance. In this work, we present a framework which exploits reasoningand semantic techniques to assist medical doctors duringthe cricothyrotomy - a well-known life-saving procedure. Morespecifically, it first acquires data in real time from a cricothyrotomysimulator, when used by medical doctors, then it stores theacquired data into a scientific database and finally it exploits anActivity Detection Engine for finding expected activities, in orderto evaluate the medical doctors' performance in real time, that isvery essential for this kind of applications. In fact, an incorrectuse of the simulator promptly detected can save the patient's life. The conducted experiments using real data show the approachefficiency and effectiveness. Eventually, we also received positivefeedbacks by the medical personnel who used our prototype.
Antinuclear Factor and Other Antibodies in Blood and Liver Diseases

Eskeland (1962) has pointed out that fatal pulmonary embolism is rare in patients below the age of 75 with fractures of the femoral neck and has suggested that anticoagulant treatment might be rtserved for this group. This is, however, the group in which control is so difficult and in which the complications of anticoagulant treatment are most common. While there can be little doubt that the mortality from embolism can be reduced in this way, it seems likely that early operation and early weight-bearing may achieve a similar effect without the risks which anticoagulant treatment involves. In these patients such a regime may make prophylactic anticoagulants unnecessary.
A Novel DOA Estimation Approach for Unknown Coherent Source Groups with Coherent Signals

In this paper, a new combination of Minimum Description Length (MDL) or Eigenvalue Gradient Method (EGM), Joint Approximate Diagonalization of Eigenmatrices (JADE) and Modified Forward-Backward Linear Prediction (MFBLP) algorithms is proposed which determines the number of non-coherent source groups and estimates the Direction Of Arrivals (DOAs) of coherent signals in each group. First, the MDL/EGM algorithm determines the number of non-coherent signal groups, and then the JADE algorithm estimates the generalized steering vectors considering white/colored Gaussian noise. Finally, the MFBLP algorithm is applied to estimate DOAs of coherent signals in each group. A new Normalized Root Mean Square Error (NRMSE) is also proposed that introduces a more realistic metric to compare the performance of DOA estimation methods. Simulation results show that the proposed algorithm can resolve sources regardless of QAM modulation size. In addition, simulations in white/colored Gaussian noises show that the proposed algorithm outperforms the JADE-MUSIC algorithm in a wide range of Signal to Noise Ratios (SNRs).
Impact of molecular mechanisms, including deletion size, on Prader–Willi syndrome phenotype: study of 75 patients

Prader–Willi syndrome (PWS) can result from a 15q11–q13 paternal deletion, maternal uniparental disomy (UPD), or imprinting mutations. We describe here the phenotypic variability detected in 51 patients with different types of deletions and 24 patients with UPD. Although no statistically significant differences could be demonstrated between the two main types of PWS deletion patients, it was observed that type I (BP1-BP3) patients acquired speech later than type II (BP2-BP3) patients. Comparing the clinical pictures of our patients with UPD with those with deletions, we found that UPD children presented with lower birth length and started walking earlier and deletion patients presented with a much higher incidence of seizures than UPD patients. In addition, the mean maternal age in the UPD group was higher than in the deletion group. No statistically significant differences could be demonstrated between the deletion and the UPD group with respect to any of the major features of PWS. In conclusion, our study did not detect significant phenotypic differences among type I and type II PWS deletion patients, but it did demonstrate that seizures were six times more common in patients with a deletion than in those with UPD.