Distributed Training Large-Scale Deep Architectures

Scale of data and scale of computation infrastructures together enable the current deep learning renaissance. However, training large-scale deep architectures demands both algorithmic improvement and careful system configuration. In this paper, we focus on employing the system approach to speed up large-scale training. Via lessons learned from our routine benchmarking effort, we first identify bottlenecks and overheads that hinter data parallelism. We then devise guidelines that help practitioners to configure an effective system and fine-tune parameters to achieve desired speedup. Specifically, we develop a procedure for setting minibatch size and choosing computation algorithms. We also derive lemmas for determining the quantity of key components such as the number of GPUs and parameter servers. Experiments and examples show that these guidelines help effectively speed up large-scale deep learning training

Instant processing of large-scale image data with FACT, a real-time cell segmentation and tracking algorithm

Quantifying cellular characteristics from a large heterogeneous population is essential to identify rare, disease-driving cells. A recent development in the combination of high-throughput screening microscopy with single-cell profiling provides an unprecedented opportunity to decipher disease-driving phenotypes. Accurately and instantly processing large amounts of image data, however, remains a technical challenge when an analysis output is required minutes after data acquisition. Here, we present fast and accurate real-time cell tracking (FACT). FACT can segment ∼20,000 cells in an average of 2.5 s (1.9–93.5 times faster than the state of the art). It can export quantifiable features minutes after data acquisition (independent of the number of acquired image frames) with an average of 90%–96% precision. We apply FACT to identify directionally migrating glioblastoma cells with 96% precision and irregular cell lineages from a 24 h movie with an average F1 score of 0.91.</p

Instant processing of large-scale image data with FACT, a real-time cell segmentation and tracking algorithm

Quantifying cellular characteristics from a large heterogeneous population is essential to identify rare, disease-driving cells. A recent development in the combination of high-throughput screening microscopy with single-cell profiling provides an unprecedented opportunity to decipher disease-driving phenotypes. Accurately and instantly processing large amounts of image data, however, remains a technical challenge when an analysis output is required minutes after data acquisition. Here, we present fast and accurate real-time cell tracking (FACT). FACT can segment ∼20,000 cells in an average of 2.5 s (1.9–93.5 times faster than the state of the art). It can export quantifiable features minutes after data acquisition (independent of the number of acquired image frames) with an average of 90%–96% precision. We apply FACT to identify directionally migrating glioblastoma cells with 96% precision and irregular cell lineages from a 24 h movie with an average F1 score of 0.91.</p

Sixteen years post radiotherapy of nasopharyngeal carcinoma elicited multi-dysfunction along PTX and chronic kidney disease with microcytic anemia

BACKGROUND: The hypothalamic–pituitary (h-p) unit is a particularly radiosensitive region in the central nervous system. As a consequence, radiation-induced irreversible, progressively chronic onset hypopituitarism (RIH) commonly develops after radiation treatments and can result in variably impaired pituitary function, which is frequently associated with increased morbidity and mortality. CASE PRESENTATION: A 38-year-old male subject, previously having received radiotherapy for treatment of nasopharygeal carcinoma (NPCA) 16 years ago, appeared at OPD complaining about his failure in penile erection, loss of pubic hair, atrophy of external genitalia: testicles reduced to 2×1.5 cm; penile size shrunk to only 4 cm long. Characteristically, he showed extremely lowered human growth hormone, (HGH, 0.115 ng/mL), testosterone (<0.1 ng/mL), total thyroxine (tT4: 4.740 g/mL), free T4 (fT4, 0.410 ng/mL), cortisol (2.34 g/dL); lowered LH (1.37 mIU/mL) and estradiol (22 pg/mL); highly elevated TSH (7.12 IU/mL). As contrast, he had low end normal ACTH, FSH, total T3, free T3, and estriol; high end normal prolactin (11.71 ng/mL), distinctly implicating hypopituitarism-induced hypothyroidism and hypogonadism. serologically, he showed severely lowered Hb (10.6 g/dL), HCT (32.7%), MCV (77.6 fL), MCH (25.3 pg), MCHC (32.6 g/dL), and platelet count (139×103/L) with extraordinarily elevated RDW (18.2%), together with severely lowered ferritin (23.6 ng/mL) and serum iron levels; highly elevated total iron binding capacity (TIBC, 509 g/dL) and transferrin (363.4 mg/dL), suggesting microcytic anemia. Severely reduced estimated glomerular filtration rate (e-GFR) (89 mL/mim/1.73 m2) pointed to CKD2. Hypocortisolemia with hyponatremia indicated secondary adrenal insufficiency. Replacement therapy using androgen, cortisol, and Ringer’s solution has shown beneficial in improving life quality. CONCLUSIONS: To our believe, we are the first group who report such complicate PTX dysfunction with adrenal cortisol insufficiency concomitantly occurring in a single patient

Down regulation of acrolein on corticosterone secretion in male rats

Acrolein is a small unsaturated aldehyde and can be found in a wide range of resources including all types of smoke and exhaust gases from gasoline engines. Although the toxicity and damage of acrolein have been recognized, the action mechanisms of acrolein, especially that of acrolein on the response of stresshormones are still unclear. The present study hypothesized that administration of acrolein altered the secretion of both adrenocorticotropin (ACTH) and corticosterone via the regulation of steroid biosynthetic pathway in rat zona fasciculata-reticularis (ZFR) cells. Both in vivo and in vitro approaches were uased. In the in vivo study, intraperitonal injection of acrolein (2 mg/ml/kg) once daily for 1 or 3 days resulted in a reduction of plasma levels of ACTH and corticosterone as well as the intracellular cAMP and ACTH-induced secretion of corticosterone. The protein expression of ACTH receptor (ACTHR) in rat ZFR cells was also reduced by 40-60% after treatment of acrolein for 1 day and 3 days, respectively. In the in vitro study, rat ZFR cells were prepared and chanllenged with ACTH (10-9 M), forskolin (an adenylyl cyclase activitior, 10-5 M), 8-Br-cAMP (a permeable synthetic cAMP, 5x10-5 M), 25-OH-cholesterol (10-5 M) ± trilostane (an inhibitor of 3?-hydroxysteroid dehydrogenase, 3?-HSD, 10-5 M). The evoked release of corticosterone by ACTH, forskolin, 8-Br-cAMP and the induced release of pregnenolone in response to 25-OH-cholesterol plus triolostane were decreased. Since the accumulation of pregnenolone after blocking 3?-HSD by trilostane represents the activity of P450scc, therate-limiting step of steroid biosynthesis, we suggest that not only the cAMP pathway was inhibited, but also the enzyme activity of P450scc was attenuated following administration of acrolein. Although insignificant, the protein expression of steroidogenic acute regulatory protein (StAR) was decreased by 40% in ZFR cells after treatment of acrolein in vivo. Incubation of ZFR cells with acrolein (10-9~10-7 M) also decreased the in vitro release of corticosterone. These results suggest that administration of acrolein inhibited corticosterone production via the attenuation of cAMP pathway, StAR protein expression, and the enzyme activity of P450scc. The attenuation of protein expression of ACTHR (also named melanocortin 2 receptor, MC2R) and reduced secrection of ACTH indicated that the hypothalamus-pituitary-adrenal (H-P-A) axis was also down- regulated by the administration of acrolein

Activation of β-Adrenoceptors by Dobutamine May Induce a Higher Expression of Peroxisome Proliferator-Activated Receptors δ (PPARδ) in Neonatal Rat Cardiomyocytes

Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors δ (PPARδ) in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARδ in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARδ expression levels and cardiac troponin I (cTnI) phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARδ expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of β1-adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARδ using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARδ is increased by dobutamine in cardiac cells

A combined targeted mutation analysis of IRF6 gene would be useful in the first screening of oral facial clefts

BACKGROUND: Interferon Regulatory Factor 6 (IRF6) is a member of the IRF family of transcription factors. It has been suggested to be an important contributor to orofacial development since mutations of the IRF6 gene has been found in Van der Woude (VWS) and popliteal pterygium syndromes (PPS), two disorders that can present with isolated cleft lip and palate. The association between IRF6 gene and cleft lip and palate has also been independently replicated in many populations. METHODS: We screened a total of 155 Taiwanese patients with cleft lip with or without cleft palate (CL/P); 31 syndromic (including 19 VWS families), 44 non-syndromic families with at least two affected members, and 80 non-syndromic patients through a combined targeted, polymerase chain reaction (PCR)-based mutation analysis for the entire coding regions of IRF6 gene. RESULTS: We found 11 mutations in 57.89% (11/19) of the VWS patients and no IRF6 mutation in 44 of the non-syndromic multiplex families and 80 non-syndromic oral cleft patients. In this IRF6 gene screening, five of these mutations (c.290 A>G, p.Tyr97Cys; c.360-375 16 bp deletion, p.Gln120HisfsX24; c.411_412 insA, p.Glu136fsX3; c.871 A>C, p.Thr291Pro; c.969 G>A, and p.Trp323X) have not been reported in the literature previously. Exon deletion was not detected in this series of IRF6 gene screening. CONCLUSIONS: Our results confirm the crucial role of IRF6 in the VWS patients and further work is needed to explore for its function in the non-syndromic oral cleft with vary clinical features

Probing the DNA kink structure induced by the hyperthermophilic chromosomal protein Sac7d

Sac7d, a small, abundant, sequence-general DNA-binding protein from the hyperthermophilic archaeon Sulfolobus acidocaldarius, causes a single-step sharp kink in DNA (∼60°) via the intercalation of both Val26 and Met29. These two amino acids were systematically changed in size to probe their effects on DNA kinking. Eight crystal structures of five Sac7d mutant–DNA complexes have been analyzed. The DNA-binding pattern of the V26A and M29A single mutants is similar to that of the wild-type, whereas the V26A/M29A protein binds DNA without side chain intercalation, resulting in a smaller overall bending (∼50°). The M29F mutant inserts the Phe29 side chain orthogonally to the C2pG3 step without stacking with base pairs, inducing a sharp kink (∼80°). In the V26F/M29F-GCGATCGC complex, Phe26 intercalates deeply into DNA bases by stacking with the G3 base, whereas Phe29 is stacked on the G15 deoxyribose, in a way similar to those used by the TATA box-binding proteins. All mutants have reduced DNA-stabilizing ability, as indicated by their lower T(m) values. The DNA kink patterns caused by different combinations of hydrophobic side chains may be relevant in understanding the manner by which other minor groove-binding proteins interact with DNA