16,059,096 research outputs found
Quasi conjunction and inclusion relation in probabilistic default reasoning
No full textWe study the quasi conjunction and the Goodman & Nguyen inclusion relation for conditional events, in the setting of probabilistic default reasoning under coherence. We deepen two recent results given in (Gilio and Sanfilippo, 2010): the first result concerns p-entailment from a family F of conditional events to the quasi conjunction C(S) associated with each nonempty subset S of F; the second result, among other aspects, analyzes the equivalence between p-entailment from F and p-entailment from C(S), where S is some nonempty subset of F. We also characterize p-entailment by some alternative theorems. Finally, we deepen the connections between p-entailment and the Goodman & Nguyen inclusion relation; in particular, for a pair (F,E|H), we study the class K of the subsets S of F such that C(S) is included in E|H. We show that K is additive and has a greatest element which can be determined by applying a suitable algorithm
Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations
No full textMatos, Liliana et al.[Background] Mutations affecting RNA splicing represent more than 20% of the mutant alleles in Sanfilippo syndrome type C, a rare lysosomal storage disorder that causes severe neurodegeneration. Many of these mutations are localized in the conserved donor or acceptor splice sites, while few are found in the nearby nucleotides.[Methods] In this study we tested several therapeutic approaches specifically designed for different splicing mutations depending on how the mutations affect mRNA processing. For three mutations that affect the donor site (c.234 + 1G > A, c.633 + 1G > A and c.1542 + 4dupA), different modified U1 snRNAs recognizing the mutated donor sites, have been developed in an attempt to rescue the normal splicing process. For another mutation that affects an acceptor splice site (c.372-2A > G) and gives rise to a protein lacking four amino acids, a competitive inhibitor of the HGSNAT protein, glucosamine, was tested as a pharmacological chaperone to correct the aberrant folding and to restore the normal trafficking of the protein to the lysosome.[Results] Partial correction of c.234 + 1G > A mutation was achieved with a modified U1 snRNA that completely matches the splice donor site suggesting that these molecules may have a therapeutic potential for some splicing mutations. Furthermore, the importance of the splice site sequence context is highlighted as a key factor in the success of this type of therapy. Additionally, glucosamine treatment resulted in an increase in the enzymatic activity, indicating a partial recovery of the correct folding.[Conclusions] We have assayed two therapeutic strategies for different splicing mutations with promising results for the future applications.This study was partially funded by a grant from the Spanish Ministry of Science and Innovation (SAF2011-25431) and from the Catalan Government (2009SGR971). We are also grateful for the permanent support, including financial aid, from 'patient-support' associations, such as Jonah's Just Begun-Foundation to Cure Sanfilippo Inc. (USA), Association Sanfilippo Sud (France), Fundación Stop Sanfilippo (Spain), Asociación MPS España (Spain). LM was supported by a grant (SFRH/BD/64592/2009) from the Fundação para a Ciência e Tecnologia IP (FCT) /POPH/FSE, Portugal, IC by a grant from the University of Barcelona (APIF), Spain and AVP by an operating grant MOP111068 from Canadian Institutes of Health Research
Theocotyle Riedel & Sanfilippo 1970
No full textGenus Theocotyle Riedel & Sanfilippo, 1970 Theocotyle venezuelensis Riedel & Sanfilippo, 1970 (Fig. 16M) Theocotyle venezuelensis Riedel & Sanfilippo, 1970: 525, pl. 6, figs 9, 10; pl. 7, figs 1, 2; 1971: 740, pl. 1, fig. 11. — Sanfilippo et al. 1985: 685, figs 25.4a-c. Cyrtophormis alta – Kozlova 1999: 155, pl. 30, fig. 7 (not 9); pl. 46, fig. 4. GEOGRAPHIC DISTRIBUTION. — Atlantic Ocean, tropical zone, Voronesh Anticline. STRATIGRAPHIC RANGE. — Late early to early middle Eocene (Sanfilippo & Riedel 1970; Sanfilippo et al. 1985; Kozlova 1999); middle to late Eocene (this study). REMARKS Cyrtophormis (?) alta (Moksyakova, 1961) holotype has no vertical rows of pores on its third segment, as it was observed for Theocotyle venezuelensis during our investigation.Published as part of Popova, Irina M., Baumgartner, Peter O., Guex, Jean, Tochilina, Svetlana V. & Glezer, Zoya I., 2002, Radiolarian biostratigraphy of Paleogene deposits of the Russian Platform (Voronesh Anticline), pp. 7-59 in Geodiversitas 24 (1) on page 50, DOI: 10.5281/zenodo.537560
Probability Propagation in Selected Aristotelian Syllogisms
No full textThis paper continues our work on a coherence-based probability semantics for Aristotelian syllogisms (Gilio, Pfeifer, and Sanfilippo, 2016; Pfeifer and Sanfilippo, 2018) by studying Figure III under coherence. We interpret the syllogistic sentence types by suitable conditional probability assessments. Since the probabilistic inference of from the premise set is not informative, we add p(M|(S ee M))>0 as a probabilistic constraint (i.e., an ``existential import assumption'') to obtain probabilistic informativeness. We show how to propagate the assigned premise probabilities to the conclusion. Thereby, we give a probabilistic meaning to all syllogisms of Figure~III. We discuss applications like generalised quantifiers (like Most are ) and (negated) default
Aging in Reverse: The Devastating Consequences of Sanfilippo Syndrome
No full textEveryone is familiar with Alzheimer’s and dementia. Many have a loved one who suffers from the disease. It is unlikely though that you have met a child who suffers from the same symptoms that progress even faster. Sanfilippo syndrome is deemed a rare disease with less than 5,000 current cases in the United States [1]. As opposed to adults who can live for years without symptoms of Alzheimer’s, Sanfilippo creeps in on vulnerable children and snatches their innocence only to realize it once it is too late. Sanfilippo syndrome is an extremely rare, genetic, metabolic disorder that mimics the brain damage found in patients with dementia or Alzheimer’s disease but in children; this article will examine the genetic causes, symptoms, and new, cutting-edge treatments.Temple University. College of Liberal ArtsPsychology and Neuroscienc
Mortality in patients with Sanfilippo syndrome
No full textAbstract Background Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) is an inherited monogenic lysosomal storage disorder divided into subtypes A, B, C and D. Each subtype is characterized by deficiency of a different enzyme participating in metabolism of heparan sulphate. The resultant accumulation of this substrate in bodily tissues causes various malfunctions of organs, ultimately leading to premature death. Eighty-four, 24 and 5 death certificates of patients with Sanfilippo syndrome types A, B and C, respectively, were obtained from the Society of Mucopolysaccharide Diseases (UK) to better understand the natural course of these conditions, covering the years 1977–2007. Results In Sanfilippo syndrome type A mean age at death (± standard deviation) was 15.22 ± 4.22 years, 18.91 ± 7.33 years for patients with Sanfilippo syndrome type B and 23.43 ± 9.47 years in Sanfilippo syndrome type C. Patients with Sanfilippo syndrome type A showed significant increase in longevity over the period of observation (p = 0.012). Survival rates of patients with Sanfilippo syndrome type B did not show a statistically significant improvement (p = 0.134). In Sanfilippo syndrome types A and B, pneumonia was identified as the leading cause of death. Conclusions The analysis of 113 death certificates of patients with Sanfilippo syndrome in the UK has demonstrated that the longevity has improved significantly in patients with Sanfilippo syndrome type A over a last few decades. The numbers of patients with Sanfilippo syndrome types B and C were too small to identify any significant trend changes for these groups. Respiratory tract infections, notably pneumonia, remain the leading cause of mortality in Sanfilippo syndrome types A and B. The extended lifespans of patients with Sanfilippo syndrome type A were achieved despite the lack of therapies to target the primary insult or pathophysiology of the disease. However, the mean age at death of these patients remains low when compared with the general population. Therefore, there is an urgent need for effective disease-specific therapies to be developed so that the quality of life and survival of patients with Sanfilippo syndrome can be improved
Analysis of Sanfilippo A gene mutations in a large pedigree.
No full textMucopolysaccharidosis type IIIA, also known as Sanfilippo A disease, results from mutations in the sulfamidase gene. To date, a total of 62 mutations have been described underlying this lysosomal disorder. Expression studies on missense mutations have shown that each alteration was disease-causing and helped to clarify the genotype-phenotype correlation. In this report we describe a large pedigree where the mutations have been identified in two second cousins: one with severe disease (E369K/R433Q) and the other with a mild form of the illness (E369K/P128L). This study places R433Q as a severe mutation underlying Sanfilippo A disease
The first case of the Sanfilippo type C syndrome in Scandinavia
No full textA Swedish patient with typical symptoms of the Sanfilippo Syndrome (Mucopolysaccharidosis III) is described. The early onset of the disease, the presence of hepatomegaly, early dementia and the absence of umbilical bernia are consistent with the subgroup Sanfilippo A. Enzyme studies indicate the diagnosis Sanfilippo C, and thus the patient represents a more severe form of this subgroup than any of the four other patients hitherto described in detail
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