Miracle-dz/UniFAR-FTUs huggingface dataset:
Management of Familial Hypercholesterolemia: A Review of the Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia

SUMMARY: Familial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism that is characterized by a significant elevation in levels of low-density lipoprotein cholesterol (LDL-C), and patients are at very high risk for premature coronary heart disease (CHD). The etiology of FH includes known mutations in the gene of the LDL receptor, LDLR; the gene of apolipoprotein B, apo B; and the proprotein convertase subtilisin/kexin type 9 gene, PCSK9. The National Lipid Association Expert Panel on Familial Hypercholesterolemia has provided recommendations for the screening and treatment of patients with FH. Early identification and aggressive treatment of FH in individual patients, as well as screening of all first-degree relatives, are recommended to minimize the risk for premature CHD. Similar to patients with conventional hypercholesterolemia, patients with FH should receive statins as initial treatment, but patients with FH may require higher doses of statins, more potent statins, statin-based combination therapy, or adjunctive therapies. Patients with FH who have additional risk factors for, or existing, cardiovascular disease or those with an inadequate response to initial statin therapy should have access to higher doses of the most efficacious statins; statins used in combination with other LDL-C–lowering agents should also be supported by formularies; additional treatments, such as LDL-C apheresis or novel therapies, may also be required to achieve acceptable LDL-C levels. New treatment approaches include mipomersen, which was approved by the FDA in January 2013. Mipomersen is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis (called an antisense inhibitor) indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-high density lipoprotein-cholesterol (non-HDL-C) levels in patients with homozygous FH (HoFH). The microsomal transfer protein lomitapide has also received FDA approval for use only in patients with HoFH. Other novel treatments currently in development include PCSK9 inhibitors. Therapies such as apheresis are likely more expensive than simple therapy with a statin but may be needed to achieve long-term reductions in complications from nonfatal and fatal cardiovascular events and hospitalizations related to myocardial infarction, cardiac revascularization, and stroke in FH patients. The cost-effectiveness of this more aggressive therapy has not been determined and should be studied. Utilization of published guidelines and the recommendations from the National Lipid Association will help to optimize the management of patients with FH.
Reiterated Wnt signaling during zebrafish neural crest development

While Wnt/β-catenin signaling is known to be involved in the development of neural crest cells in zebrafish, it is unclear which Wnts are involved, and when they are required. To address these issues we employed a zebrafish line that was transgenic for an inducible inhibitor of Wnt/β-catenin signaling, and inhibited endogenous Wnt/β-catenin signaling at discrete times in development. Using this approach, we defined a critical period for Wnt signaling in the initial induction of neural crest, which is distinct from the later period of development when pigment cells are specified from neural crest. Blocking Wnt signaling during this early period interfered with neural crest formation without blocking development of dorsal spinal neurons. Transplantation experiments suggest that neural crest precursors must directly transduce a Wnt signal. With regard to identifying which endogenous Wnt is responsible for this initial critical period, we established that wnt8 is expressed in the appropriate time and place to participate in this process. Supporting a role for Wnt8, blocking its function with antisense morpholino oligonucleotides eliminates initial expression of neural crest markers. Taken together, these results demonstrate that Wnt signals are critical for the initial induction of zebrafish neural crest and suggest that this signaling pathway plays reiterated roles in its development.
Effectiveness of Pandemic and Seasonal Influenza Vaccines in Preventing Laboratory-Confirmed Influenza in Adults: A Clinical Cohort Study during Epidemic Seasons 2009–2010 and 2010–2011 in Finland

Background One dose of pandemic influenza vaccine Pandemrix (GlaxoSmithKline) was offered to the entire population of Finland in 2009–10. We conducted a prospective clinical cohort study to determine the vaccine effectiveness in preventing febrile laboratory-confirmed influenza infection during the influenza season 2009–10 and continued the study in 2010–11. Methods In total, 3,518 community dwelling adults aged 18–75 years living in Tampere city were enrolled. The participants were not assigned to any vaccination regimen, but they could participate in the study regardless of their vaccination status or intention to be vaccinated with the pandemic or seasonal influenza vaccine. They were asked to report if they received Pandemrix in 2009–10 and/or trivalent influenza vaccine in 2010–11. Vaccinations were verified from medical records. The participants were instructed to report all acute symptoms of respiratory tract infection with fever (at least 38°C) and pneumonias to the study staff. Nasal and oral swabs were obtained within 5–7 days after symptom onset and influenza-specific RNA was identified by reverse transcription polymerase chain reaction. Results In 2009–10, the estimated vaccine effectiveness was 81% (95%CI 30–97). However, the vaccine effectiveness could not be estimated reliably, because only persons in prioritized groups were vaccinated before/during the first pandemic wave and many participants were enrolled when they already had the symptoms of A(H1N1)pdm09 influenza infection. In 2010–11, 2,276 participants continued the follow-up. The vaccine effectiveness, adjusted for potential confounding factors was 81% (95%CI 41–96) for Pandemrix only and 88% (95%CI 63–97) for either Pandemrix or trivalent influenza vaccine 2010–11 or both, respectively. Conclusion Vaccination with an AS03-adjuvanted pandemic vaccine in 2009–10 was still effective in preventing A(H1N1)pdm09 influenza during the following epidemic season in 2010–11. Trial Registration ClinicalTrials.gov NCT01024725. NCT01206114.
Generalized integrated brownian fields for simulation metamodeling

We use Gaussian random fields (GRFs) that we call generalized integrated Brownian fields (GIBFs), whose covariance functions have been studied in the context of reproducing kernels, for Gaussian process modeling. We introduce GIBFs into the fields of deterministic and stochastic simulation metamodeling, and give a probabilistic representation of GIBFs that is not given in the literature on reproducing kernels. These GIBFs have differentiability that can be controlled in each coordinate, and are built from GRFs which have the Markov property. Furthermore, we introduce a new parameterization of GIBFs which allows them to be used in higher-dimensional metamodeling problems. We also show how to implement stochastic kriging with GIBFs, covering trend modeling and fitting. Lastly, we use tractable examples to demonstrate superior prediction ability as compared to the GRF corresponding to the Gaussian covariance function.
Ontology instance matching by considering semantic link cloud

The proliferation of heterogeneous sources of instances raises a research issue of achieving interoperability through instance matching. In this paper, we propose an efficient algorithm for ontology instance matching by considering the semantic links associated to a particular instance. An instance is specified explicitly with the help of linked concepts, properties and their values in a neighborhood. We refer these neighboring links of an instance as a "Semantic Link Cloud (SLC)" in a collection. We compare SLCs to align ontology instances across heterogeneous sources of ontology knowledge base. Our algorithm shows its efficiency over various transformations of a dataset: value transformation, logical and structural transformation.
Genetic algorithm for exam proctor schedule

This research was aimed to present the methodology of genetic algorithm for exam proctor schedules used in educational institutes. The purpose of the study is to cut down time for organizing each staff's proctoring table. Every staff has equal of proctoring during normal and extra workload. It is also able to avoid exam proctoring on weekend and on the staff engaged duration. In the experiment, the 4 parameter means in the method of genetic algorithm including the number of population, the probability of crossover, the probability of mutation and the maximum number of generations have been adjusted to suit the most appropriate mean. It was found that the staff's proctoring table derived from method of the genetic algorithm can be applied to arrange the lecturers' exam proctoring tables effectively. The result is the proctoring tables that have the numbers of exam proctoring on the normal and extra workload are equal. It is also able to avoid exam proctoring on weekend and on the staff engaged duration.
Un sistema para la segmentación en proposiciones de textos en español

Resumen: Se describe un sistema dedicado al reconocimiento de proposiciones y de las relaciones jerarquicas entre ellas, para textos en espanol. Dicho sistema fue concebido para brindar un servicio de base a tareas de extraccion de informacion de texto y de analisis sintactico. El sistema opera a partir de los resultados de un etiquetador probabilistico. Los conocimientos linguisticos se expresan en un formalismo de reglas de reescritura, con reglas que permiten una especificacion parcial de la parte de reescritura y tomar en cuenta el texto que rodea esta parte (contexto). La descripcion se centra en la organizacion de las reglas en modulos que atacan distintos tipos de problemas linguisticos, mostrando las sucesivas etapas del analisis completo de una oracion ejemplo.
MortalityPredictors.org: a manually-curated database of published biomarkers of human all-cause mortality

Biomarkers of all-cause mortality are of tremendous clinical and research interest. Because of the long potential duration of prospective human lifespan studies, such biomarkers can play a key role in quantifying human aging and quickly evaluating any potential therapies. Decades of research into mortality biomarkers have resulted in numerous associations documented across hundreds of publications. Here, we present MortalityPredictors.org, a manually-curated, publicly accessible database, housing published, statistically-significant relationships between biomarkers and all-cause mortality in population-based or generally healthy samples. To gather the information for this database, we searched PubMed for appropriate research papers and then manually curated relevant data from each paper. We manually curated 1,576 biomarker associations, involving 471 distinct biomarkers. Biomarkers ranged in type from hematologic (red blood cell distribution width) to molecular (DNA methylation changes) to physical (grip strength). Via the web interface, the resulting data can be easily browsed, searched, and downloaded for further analysis. MortalityPredictors.org provides comprehensive results on published biomarkers of human all-cause mortality that can be used to compare biomarkers, facilitate meta-analysis, assist with the experimental design of aging studies, and serve as a central resource for analysis. We hope that it will facilitate future research into human mortality and aging.
Genetic Labeling of Neuronal Subsets through Enhancer Trapping in Mice

The ability to label, visualize, and manipulate subsets of neurons is critical for elucidating the structure and function of individual cell types in the brain. Enhancer trapping has proved extremely useful for the genetic manipulation of selective cell types in Drosophila. We have developed an enhancer trap strategy in mammals by generating transgenic mice with lentiviral vectors carrying single-copy enhancer-detector probes encoding either the marker gene lacZ or Cre recombinase. This transgenic strategy allowed us to genetically identify a wide variety of neuronal subpopulations in distinct brain regions. Enhancer detection by lentiviral transgenesis could thus provide a complementary method for generating transgenic mouse libraries for the genetic labeling and manipulation of neuronal subsets.
Comprehensive Transcriptome Analysis Unravels the Existence of Crucial Genes Regulating Primary Metabolism during Adventitious Root Formation in Petunia hybrida

To identify specific genes determining the initiation and formation of adventitious roots (AR), a microarray-based transcriptome analysis in the stem base of the cuttings of Petunia hybrida (line W115) was conducted. A microarray carrying 24,816 unique, non-redundant annotated sequences was hybridized to probes derived from different stages of AR formation. After exclusion of wound-responsive and root-regulated genes, 1,354 of them were identified which were significantly and specifically induced during various phases of AR formation. Based on a recent physiological model distinguishing three metabolic phases in AR formation, the present paper focuses on the response of genes related to particular metabolic pathways. Key genes involved in primary carbohydrate metabolism such as those mediating apoplastic sucrose unloading were induced at the early sink establishment phase of AR formation. Transcriptome changes also pointed to a possible role of trehalose metabolism and SnRK1 (sucrose non-fermenting 1- related protein kinase) in sugar sensing during this early step of AR formation. Symplastic sucrose unloading and nucleotide biosynthesis were the major processes induced during the later recovery and maintenance phases. Moreover, transcripts involved in peroxisomal beta-oxidation were up-regulated during different phases of AR formation. In addition to metabolic pathways, the analysis revealed the activation of cell division at the two later phases and in particular the induction of G1-specific genes in the maintenance phase. Furthermore, results point towards a specific demand for certain mineral nutrients starting in the recovery phase.
Performance and Power Spectrum Calculations for Convolutionally Coded Generalized MSK with Two Symbol Periods Pulse Shape Duration

We show that by applying a cascaded convolutional encoder using two stages of coding, the last being a double repetition code, to "preceded" generalized minimum-shift keying (MSK) signals with pulse shape of duration two symbol periods a significant improvement in power and spectral efficiency is achieved. With only a double repetition code, it is shown that the signal has a power spectrum identical to uncoded MSK-like. When outer encoder is applied to improve the power efficiency, the bandwidth expansion is just a reciprocal of the outer encoder rate. It is demonstrated that considering performance, bandwidth and receiver complexity, generalized MSK signal coded using our special cascaded convolutional codes is an improvement over MSK and generalized MSK coded with "optimum" convolutional codes for the same code rate and receiver complexity reported previously for the same modulation scheme.
Multichannel communications in vehicular Ad Hoc networks: a survey

Vehicular ad hoc networks are the key to provisioning safety-critical and commercial services on the road. Multiple channels are assigned in the 5 GHz spectrum to support these services. In this article an overview of the multichannel architecture proposed by standardization bodies in the United States and Europe is presented. The main contribution is the identification of the open challenges for multichannel coordination, synchronization, and access. Discussions on related countermeasures, fully explored in neither the standards nor the scientific literature, aim to serve as guidelines for designers of future protocols and applications in vehicular environments.
Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides

We have developed an in situ hybridization procedure for the detection of microRNAs (miRNAs) in tissue sections from mouse embryos and adult organs. The method uses highly specific washing conditions for RNA oligonucleotide probes conjugated to a fluorescein hapten. We show that this method detects predominantly mature miRNAs rather than the miRNA precursors or primary transcripts. We have determined expression patterns for several miRNAs expressed in the developing and adult nervous system, including miR‐124a, miR‐9, miR‐92, and miR‐204. Whereas miR‐124a is expressed in neurons, miR‐9 is expressed in neural progenitors and some neurons, and miR‐204 is expressed in the choroid plexus, retinal pigment epithelium, and ciliary body. miR‐204 is located in an intron of the TRPM3 gene, and the TRPM3 mRNA is coexpressed with miR‐204 in the choroid plexus. We also find that primary transcripts for miR‐124a and miR‐9 genes are expressed in patterns similar to their respective mature miRNAs. The ability to visualize expression of specific miRNAs in embryos and tissues should aid studies on miRNA function. Developemental Dynamics 235:2538–2548, 2006. © 2006 Wiley‐Liss, Inc.
Nixon, Rob (2011), Slow Violence and the Environmentalism of the Poor

Tradicionalmente, las sociedades del Norte Global han asociado las crisis ecologicas y medioambientales con eventos de gran envergadura, espectaculares, de gran visibilidad y/o repercusion mediatica. Algunos casos que ejemplifican dicha percepcion pueden ser los “accidentes” nucleares en Chernobil y Fukushima, los derrames de petroleo causados por el Prestige en el 2002 en las costas europeas y el causado por el Deepwater Horizon en el Golfo de Mexico en el 2010, los “desastres naturales” tal.
An N-terminal Arginine-rich Cluster and a Proline-Alanine-Threonine Repeat Region Determine the Cellular Localization of the Herpes Simplex Virus Type 1 ICP34.5 Protein and Its Ligand, Protein Phosphatase 1*

The ICP34.5 protein facilitates herpes simplex virus replication by binding and activating protein phosphatase 1 (PP1) by means of a very conserved C-terminal GADD34-like region. Natural variants of the ICP34.5 differing in the number of arginines in an Arg-rich cluster at the N terminus and the number of Pro-Ala-Thr repeats in the central bridge region of the protein were cloned as fusion proteins with a reporter peptide (c-Myc or hrGFP) at the C terminus. The natural variants were obtained from strains differing in passage history, tissue culture behavior, and neuroinvasive disease potential. In transfected cells, these variants localized to different subcellular compartments. The N-terminal Arg-rich cluster acted as a cellular localization signal for discrete regions of the nucleus and cytoplasm, but the ultimate location of ICP34.5 was determined by the number of Pro-Ala-Thr repeats in the central bridge region. PP1 colocalized with the ICP34.5 variant in cells expressing the ICP34.5. The ICP34.5-mediated, herpes simplex virus strain-dependent differences in the modulation of PP1 location and function may be responsible for the strain-associated differences in tissue culture behavior and virulence of the virus.
Rapid protein expression in mammalian cells

These Ecole polytechnique federale de Lausanne EPFL, n° 2473 (2001)Faculte des sciences de baseInstitut interfacultaire de Bioingenierie (SV/STI)Laboratoire de biotechnologie cellulaire (SV/STI/SB)Jury: Hanspeter Amstutz, Michael Graetzel, Urs von Stockar, Roland Wagner Public defense: 2001-11-30 Reference doi:10.5075/epfl-thesis-2473Print copy in library catalog Record created on 2005-03-16, modified on 2016-08-08
Left ventricular volumes by echocardiography in chronic aortic and mitral regurgitations

ABSTRACT Objectives Cut-off values for left ventricular (LV) dimensions indicating severe valve regurgitation have not been defined. The aim of this study was to establish echocardiographic cut-off values for LV dimensions indicating severe chronic aortic (AR) or mitral (MR) regurgitation. Design The hemodynamic significance was confirmed by documented reduction of end-diastolic volume (EDV) and symptom relief after surgery. Eighty-three patients with moderate or severe regurgitation (AR, n = 41; MR, n = 42) without other cardiac conditions underwent prospectively two-dimensional (2DE), real-time three-dimensional (RT3DE) echocardiography and cardiovascular magnetic resonance (CMR) exams within 4 h. Results The relationship between EDVCMR and EDV2DE and EDVRT3DE were strong (R 0.95 and 0.91). EDV index cut-offs for 2DE/RT3DE >87/104 ml/m2 identified AR patients with severe regurgitation with a positive likelihood ratio (PLR) of 5.0/5.0. The corresponding in patients with MR EDV index cut-offs were >69/87 ml/m2 with a PLR of 14.9/5.5. LV linear dimensions could not identify patients with severe regurgitation. Conclusions LV volumes by echocardiography can support the diagnosis of severe chronic regurgitation. Importantly, other causes for LV enlargement have to be considered.
An approach to rapid prototyping of large multi-agent systems

Engineering individual components of a multi-agent system and their interactions is a complex and error-prone task in urgent need of methods and tools. Prototyping is a valuable technique to help software engineers explore the design space while gaining insight and a "feel" for the dynamics of the system; prototyping also allows engineers to learn more about the relationships among design features and the desired computational behaviour. In this paper we describe an approach to building prototypes of large multi-agent systems with which we can experiment and analyse results. We have implemented an environment embodying our approach. This environment is supported by a distributed platform that helps us achieve controlled simulations.