Open-lexicon Language Modeling Combining Word and Character Levels

Abstract—In this paper we investigate different n-gram language models that are defined over an open lexicon. We introduce a character-level language model and combine it with a standard word-level language model in a backoff fashion. The character-level language model is redefined and renormalized to assign zero probability to words from a fixed vocabulary. Furthermore we present a way to interpolate language models created at the word and character levels. The computation of character-level probabilities incorporates the across-word context. We compare perplexities on all words from the test set and on in-lexicon and OOV words separately on corpora of English and Arabic text. I

Coexistence of Gilbert syndrome with hereditary haemolytic anaemias.

Genotyping of the UGT1A1 gene showed distinct distribution of the common A(TA)(n)TAA polymorphism relative to other European populations. Because of a greater risk of hyperbilirubinaemia due to hereditary haemolytic anaemia, the diagnosis of Gilbert syndrome in this group of patients is very important

Au-198-Coated Superparamagnetic Iron Oxide Nanoparticles for Dual Magnetic Hyperthermia and Radionuclide Therapy of Hepatocellular Carcinoma

This study was performed to synthesize a radiopharmaceutical designed for multimodal hepatocellular carcinoma (HCC) treatment involving radionuclide therapy and magnetic hyperthermia. To achieve this goal, the superparamagnetic iron oxide (magnetite) nanoparticles (SPIONs) were covered with a layer of radioactive gold (Au-198) creating core-shell nanoparticles (SPION@Au). The synthesized SPION@Au nanoparticles exhibited superparamagnetic properties with a saturation magnetization of 50 emu/g, which is lower than reported for uncoated SPIONs (83 emu/g). Nevertheless, the SPION@Au core-shell nanoparticles showed a sufficiently high saturation magnetization value which allows them to reach a temperature of 43 degrees C at a magnetic field frequency of 386 kHz. The cytotoxic effect of nonradioactive and radioactive SPION@Au-polyethylene glycol (PEG) bioconjugates was carried out by treating HepG2 cells with various concentrations (1.25-100.00 mu g/mL) of the compound and radioactivity in range of 1.25-20 MBq/mL. The moderate cytotoxic effect of nonradioactive SPION@Au-PEG bioconjugates on HepG2 was observed. The cytotoxic effect associated with the beta(-) radiation emitted by Au-198 was much greater and already reaches a cell survival fraction below 8% for 2.5 MBq/mL of radioactivity after 72 h. Thus, the killing of HepG2 cells in HCC therapy should be possible due to the combination of the heat-generating properties of the SPION-Au-198-PEG conjugates and the radiotoxicity of the radiation emitted by Au-198

Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond–Blackfan anemia

International audienc

Biallelic loss of CDKN2A is associated with poor response to treatment in pediatric acute lymphoblastic leukemia

The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous. Patients with CDKN2A homozygous deletions were older at diagnosis (p < .001), more frequently steroid resistant (p = .049), had higher WBC count (p < .001), higher MRD at Day 15 (p = .013) and lower relapse-free survival [p = .028, hazard ratio: 2.28 (95% confidence interval: 1.09-4.76)] than patients without these alterations. CDKN2A homozygous deletions coexisted with IKZF1 and PAX5 deletions (p < .001). In conclusion, CDKN2A homozygous deletions, but not promoter methylation, are associated with poor response to treatment and increased relapse risk of pediatric BCP-ALL.status: publishe

Ribosomal Protein Genes RPS10 and RPS26 Are Commonly Mutated in Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA), an inherited bone marrow failure syndrome characterized by anemia that usually presents before the first birthday or in early childhood, is associated with birth defects and an increased risk of cancer. Although anemia is the most prominent feature of DBA, the disease is also characterized by growth retardation and congenital malformations, in particular craniofacial, upper limb, heart, and urinary system defects that are present in ∼30%–50% of patients. DBA has been associated with mutations in seven ribosomal protein (RP) genes, RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, and RPS7, in about 43% of patients. To continue our large-scale screen of RP genes in a DBA population, we sequenced 35 ribosomal protein genes, RPL15, RPL24, RPL29, RPL32, RPL34, RPL9, RPL37, RPS14, RPS23, RPL10A, RPS10, RPS12, RPS18, RPL30, RPS20, RPL12, RPL7A, RPS6, RPL27A, RPLP2, RPS25, RPS3, RPL41, RPL6, RPLP0, RPS26, RPL21, RPL36AL, RPS29, RPL4, RPLP1, RPL13, RPS15A, RPS2, and RPL38, in our DBA patient cohort of 117 probands. We identified three distinct mutations of RPS10 in five probands and nine distinct mutations of RPS26 in 12 probands. Pre-rRNA analysis in lymphoblastoid cells from patients bearing mutations in RPS10 and RPS26 showed elevated levels of 18S-E pre-rRNA. This accumulation is consistent with the phenotype observed in HeLa cells after knockdown of RPS10 or RPS26 expression with siRNAs, which indicates that mutations in the RPS10 and RPS26 genes in DBA patients affect the function of the proteins in rRNA processing

Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia

Diamond-Blackfan anemia (DBA) is an inherited form of pure red cell aplasia that usually presents in infancy or early childhood and is associated with congenital malformations in approximately 30-50% of patients. DBA has been associated with mutations in nine ribosomal protein (RP) genes in about 53% of patients. We completed a large-scale screen of 79 RP genes by sequencing 16 RP genes (RPL3, RPL7, RPL8, RPL10, RPL14, RPL17, RPL19, RPL23A, RPL26, RPL27, RPL35, RPL36A, RPL39, RPS4X, RPS4Y1, and RPS21) in 96 DBA probands. We identified a de novo two-nucleotide deletion in RPL26 in one proband associated with multiple severe physical abnormalities. This mutation gives rise to a remarkable ribosome biogenesis defect that affects maturation of both the small and the large subunits. We also found a deletion in RPL19 and missense mutations in RPL3 and RPL23A, which may be variants of unknown significance. Together with RPL5, RPL11, and RPS7, RPL26 is the fourth RP regulating p53 activity that is linked to DBA