Identification of Mixtures of Discrete Product Distributions in Near-Optimal Sample and Time Complexity

We consider the problem of identifying, from statistics, a distribution of discrete random variables $X_1,\ldots,X_n$ that is a mixture of $k$ product distributions. The best previous sample complexity for $n \in O(k)$ was $(1/\zeta)^{O(k^2 \log k)}$ (under a mild separation assumption parameterized by $\zeta$). The best known lower bound was $\exp(\Omega(k))$. It is known that $n\geq 2k-1$ is necessary and sufficient for identification. We show, for any $n\geq 2k-1$, how to achieve sample complexity and run-time complexity $(1/\zeta)^{O(k)}$. We also extend the known lower bound of $e^{\Omega(k)}$ to match our upper bound across a broad range of $\zeta$. Our results are obtained by combining (a) a classic method for robust tensor decomposition, (b) a novel way of bounding the condition number of key matrices called Hadamard extensions, by studying their action only on flattened rank-1 tensors

Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay

Purpose: To identify novel genes associated with intellectual disability (ID) in four unrelated families. Methods: Here, through exome sequencing and international collaboration, we report eight individuals from four unrelated families of diverse geographic origin with biallelic loss-of-function variants in UBE4A. Results: Eight evaluated individuals presented with syndromic intellectual disability and global developmental delay. Other clinical features included hypotonia, short stature, seizures, and behavior disorder. Characteristic features were appreciated in some individuals but not all; in some cases, features became more apparent with age. We demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioral abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals. Conclusion: These data indicate that biallelic loss-of-function variants in UBE4A cause a novel intellectual disability syndrome, suggesting that UBE4A enzyme activity is required for normal development and neurological function

Stellar Collisions During Binary-Binary and Binary-Single Star Interactions

Physical collisions between stars occur frequently in dense star clusters, either via close encounters between two single stars, or during strong dynamical interactions involving binary stars. Here we study stellar collisions that occur during binary-single and binary-binary interactions, by performing numerical scattering experiments. Our results include cross sections, branching ratios, and sample distributions of parameters for various outcomes. For interactions of hard binaries containing main-sequence stars, we find that the normalized cross section for at least one collision to occur (between any two of the four stars involved) is essentially unity, and that the probability of collisions involving more than two stars is significant. Hydrodynamic calculations have shown that the effective radius of a collision product can be 2-30 times larger than the normal main-sequence radius for a star of the same total mass. We study the effect of this expansion, and find that it increases the probability of further collisions considerably. We discuss these results in the context of recent observations of blue stragglers in globular clusters with masses exceeding twice the main-sequence turnoff mass. We also present Fewbody, a new, freely available numerical toolkit for simulating small-N gravitational dynamics that is particularly suited to performing scattering experiments.Comment: Accepted for publication in MNRAS; 29 pages, 22 figures, 7 table

Genetic variants of Anaplasma phagocytophilum from 14 equine granulocytic anaplasmosis cases

<p>Abstract</p> <p>Background</p> <p>Equine Granulocytic Anaplasmosis (EGA) is caused by <it>Anaplasma phagocytophilum</it>, a tick-transmitted, obligate intracellular bacterium. In Europe, it is transmitted by <it>Ixodes ricinus</it>. A large number of genetic variants of <it>A. phagocytophilum </it>circulate in nature and have been found in ticks and different animals. Attempts have been made to assign certain genetic variants to certain host species or pathologies, but have not been successful so far. The purpose of this study was to investigate the causing agent <it>A. phagocytophilum </it>of 14 cases of EGA in naturally infected horses with molecular methods on the basis of 4 partial genes (<it>16S rRNA</it>, <it>groEL</it>, <it>msp2</it>, and <it>msp4</it>).</p> <p>Results</p> <p>All DNA extracts of EDTA-blood samples of the horses gave bands of the correct nucleotide size in all four genotyping PCRs. Sequence analysis revealed 4 different variants in the partial <it>16S rRNA</it>, <it>groEL </it>gene and <it>msp2 </it>genes, and 3 in the <it>msp4 </it>gene. One <it>16S rRNA </it>gene variant involved in 11 of the 14 cases was identical to the "prototype" variant causing disease in humans in the amplified part [GenBank: <ext-link ext-link-id="U02521" ext-link-type="gen">U02521</ext-link>]. Phylogenetic analysis revealed as expected for the <it>groEL </it>gene that sequences from horses clustered separately from roe deer. Sequences of the partial <it>msp2 </it>gene from this study formed a separate cluster from ruminant variants in Europe and from all US variants.</p> <p>Conclusions</p> <p>The results show that more than one variant of <it>A. phagocytophilum </it>seems to be involved in EGA in Germany. The comparative genetic analysis of the variants involved points towards different natural cycles in the epidemiology of <it>A. phagocytophilum</it>, possibly involving different reservoir hosts or host adaptation, rather than a strict species separation.</p

A Novel Role for the Centrosomal Protein, Pericentrin, in Regulation of Insulin Secretory Vesicle Docking in Mouse Pancreatic β-cells

The centrosome is important for microtubule organization and cell cycle progression in animal cells. Recently, mutations in the centrosomal protein, pericentrin, have been linked to human microcephalic osteodysplastic primordial dwarfism (MOPD II), a rare genetic disease characterized by severe growth retardation and early onset of type 2 diabetes among other clinical manifestations. While the link between centrosomal and cell cycle defects may account for growth deficiencies, the mechanism linking pericentrin mutations with dysregulated glucose homeostasis and pre-pubertal onset of diabetes is unknown. In this report we observed abundant expression of pericentrin in quiescent pancreatic β-cells of normal animals which led us to hypothesize that pericentrin may have a critical function in β-cells distinct from its known role in regulating cell cycle progression. In addition to the typical centrosome localization, pericentrin was also enriched with secretory vesicles in the cytoplasm. Pericentrin overexpression in β-cells resulted in aggregation of insulin-containing secretory vesicles with cytoplasmic, but not centrosomal, pericentriolar material and an increase in total levels of intracellular insulin. RNAi- mediated silencing of pericentrin in secretory β-cells caused dysregulated secretory vesicle hypersecretion of insulin into the media. Together, these data suggest that pericentrin may regulate the intracellular distribution and secretion of insulin. Mice transplanted with pericentrin-depleted islets exhibited abnormal fasting hypoglycemia and inability to regulate blood glucose normally during a glucose challenge, which is consistent with our in vitro data. This previously unrecognized function for a centrosomal protein to mediate vesicle docking in secretory endocrine cells emphasizes the adaptability of these scaffolding proteins to regulate diverse cellular processes and identifies a novel target for modulating regulated protein secretion in disorders such as diabetes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluasi Fungsi Insinerator Dalam Memusnahkan Limbah B3 Di Rumah Sakit NI Dr.Ramelan Surabaya

Pengelolaan limbah padat B3 di Rumah Sakit TNI Angkatan Laut Dr. Ramelan sangat penting diperhatikan karena dapat berdampak buruk apabila tidak dikelola dengan baik. Oleh sebab itu diperlukan adanya penelitian untuk mengidentifikasi jumlah timbulan dan penanganan limbah padat B3, mengevaluasi manajemen, penyimpanan sementara serta mengevaluasi proses insinerasi. Evaluasi fungsi incinerator di Rumah Sakit TNI Angkatan Laut Dr. Ramelan dilakukan dengan meneliti jumlah timbulan limbah B3, kapasitas pembakaran insinerator, suhu pembakaran insinerator, densitas limbah dan abu pembakaran, dan tes TCLP residu pembakaran incinerator Rumah Sakit TNI Angkatan Laut Dr. Ramelan. Dalam penelitian ini, Rumkital Dr. Ramelan memusnahkan limbah dengan incinerator. Limbah B3 yang dihasilkan Rumkital Dr. Ramelan dimusnakan dengan satu incinerator dengan type KAMINE TYPE BDR-INC 10. Limbah yang dimusnahkan di Rumkital Dr. Ramelan berasal dari Rumkital Dr. Ramelan dan Lantamal Perak. Setelah dilakukan penelitian langsung selama 14 hari berturut-turut, didapatkan bahwa rata-rata timbulan limbah B3 di Rumkital Dr. Ramelan adalah 89.98 Kg/hari dan dengan densitas rata-rata limbah ialah 166,67 kg/m3. Tinggat removal dari pembakaran limbah dengan incinerator di Rumah Sakit TNI Angkatan Laut Dr. Ramelan ialah 82,63%. Pengelolaan abu sisa incinerator Rumkital Dr. Ramelan belum sesuai dengan peraturan yang berlaku dan dari penelitian yang dilakukan yaitu pengujian kandungan abu incinerator, solidifikasi abu incinerator dengan perbandingan semen:abu adalah 1:3 dan uji TCLP, didapatkan bahwa limbah abu sisa insinerator Rumah Sakit TNI Angkatan Laut Dr. Ramelan Surabaya, dapat ditimbun pada landfill kategori I sesuai dengan Keputusan Kepala Bapedal No.4 Tahun 1995