Slow Passage through a Saddle-Node Bifurcation in Discrete Dynamical Systems

We study a discrete non-autonomous system whose autonomous counterpart (with the frozen bifurcation parameter) admits a saddle-node bifurcation, and in which the bifurcation parameter slowly changes in time and is characterized by a sweep rate constant $\epsilon$. The discrete system is more appropriate for modeling realistic systems since only time series data is available. We show that in contrast to its autonomous counterpart, when the time mesh size $\Delta t$ is less than the order $O(\epsilon)$, there is a bifurcation delay as the bifurcation time-varying parameter is varied through the bifurcation point, and the delay is proportional to the two-thirds power of the sweep rate constant $\epsilon$. This bifurcation delay is significant in various realistic systems since it allows one to take necessary action promptly before a sudden collapse or shift to different states. On the other hand, when the time mesh size $\Delta t$ is larger than the order $o(\epsilon)$, the dynamical behavior of the solution is dramatically changed before the bifurcation point. This behavior is not observed in the autonomous counterpart. Therefore, the dynamical behavior of the system strongly depends on the time mesh size. Finally. due to the very discrete feature of the system, there are no efficient tools for the analytical study of the system. Our approach is elementary and analytical

Bioavailable testosterone predicts a lower risk of Alzheimer’s disease in older men: a 1-year cohort study

Oral Presentationpublished_or_final_versionThe 15th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16, suppl. 1, p. 16, abstract no. 1

Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study

Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells. After 24-h treatment with MTH-3, a concentration-dependent decrease in MDA-MB-231 cell viability was observed, and the IC50 value was 5.37±1.22 μM. MTH-3 significantly triggered G2/M phase arrest and apoptosis in MDA-MB-231 cells. Within a 24-h treatment, MTH-3 decreased the CDK1 activity by decreasing CDK1 and cyclin B1 protein levels. MTH-3-induced apoptosis was further confirmed by morphological assessment and Annexin V/PI staining assay. Induction of apoptosis caused by MTH-3 was accompanied by an apparent increase of DR3, DR5 and FADD and, as well as a marked decrease of Bcl-2 and Bcl-xL protein expression. MTH-3 also decreased the protein levels of Ero1, PDI, PERK and calnexin, as well as increased the expression of IRE1α, CHOP and Bip that consequently led to ER stress and MDA-MB-231 cell apoptosis. In addition, MTH-3-treated cells were involved in the autophagic process and cleavage of LC3B was observed. MTH-3 enhanced the protein levels of LC3B, Atg5, Atg7, Atg12, p62 and Beclin-1 in MDA-MB-231 cells. Finally, DNA microarray was carried out to investigate the level changes of gene expression modulated by MTH-3 in MDA-MB-231 cells. Taken together, our results suggest that MTH-3 might be a novel therapeutic agent for the treatment of triple-negative breast cancer in the near future

More than 7-year survival of a patient following repeat hepatectomy for total 20 colon cancer liver metastases

A 54-year-old man was transferred with sigmoid colon cancer combined with multiple bilobar liver metastases. Nine metastases were in the left lobe and 5 metastases were in the right lobe. After low anterior resection, all 9 lesions in the left lobe were completely removed by wedge resections. Because the remnant liver volume after multiple wedge resection of the left lobe was not sufficient to perform a right hepatectomy simultaneously, we planned a two-stage hepatectomy. Right portal vein embolization was performed one week after the first liver operation. A right hepatectomy was safely performed 22 days after the first hepatectomy. A recurrent mass developed in the segment III 18 months after the right hepatectomy. Radiofrequency ablation (RFA) was performed to remove that lesion. Five other metastases developed 18 months after RFA whereby multiple wedge resections were performed. The patient has survived for more than 7 years after the first liver operation

An adaptive prefix-assignment technique for symmetry reduction

This paper presents a technique for symmetry reduction that adaptively assigns a prefix of variables in a system of constraints so that the generated prefix-assignments are pairwise nonisomorphic under the action of the symmetry group of the system. The technique is based on McKay's canonical extension framework [J.~Algorithms 26 (1998), no.~2, 306--324]. Among key features of the technique are (i) adaptability---the prefix sequence can be user-prescribed and truncated for compatibility with the group of symmetries; (ii) parallelizability---prefix-assignments can be processed in parallel independently of each other; (iii) versatility---the method is applicable whenever the group of symmetries can be concisely represented as the automorphism group of a vertex-colored graph; and (iv) implementability---the method can be implemented relying on a canonical labeling map for vertex-colored graphs as the only nontrivial subroutine. To demonstrate the practical applicability of our technique, we have prepared an experimental open-source implementation of the technique and carry out a set of experiments that demonstrate ability to reduce symmetry on hard instances. Furthermore, we demonstrate that the implementation effectively parallelizes to compute clusters with multiple nodes via a message-passing interface.Comment: Updated manuscript submitted for revie

Linear Magnetoelectric Phase in Ultrathin MnPS₃ Probed by Optical Second Harmonic Generation

The transition metal thiophosphates MPS₃ (M=Mn, Fe, Ni) are a class of van der Waals stacked insulating antiferromagnets that can be exfoliated down to the ultrathin limit. MnPS₃ is particularly interesting because its Néel ordered state breaks both spatial-inversion and time-reversal symmetries, allowing for a linear magnetoelectric phase that is rare among van der Waals materials. However, it is unknown whether this unique magnetic structure of bulk MnPS₃ remains stable in the ultrathin limit. Using optical second harmonic generation rotational anisotropy, we show that long-range linear magnetoelectric type Néel order in MnPS₃ persists down to at least 5.3 nm thickness. However an unusual mirror symmetry breaking develops in ultrathin samples on SiO₂ substrates that is absent in bulk materials, which is likely related to substrate induced strain

Isotope effect on the transition temperature TcT_c in Fe-based superconductors: the current status

The results of the Fe isotope effect (Fe-IE) on the transition temperature $T_c$ obtained up to date in various Fe-based high temperature superconductors are summarized and reanalyzed by following the approach developed in [Phys. Rev. B 82, 212505 (2010)]. It is demonstrated that the very controversial results for Fe-IE on $T_c$ are caused by small structural changes occurring simultaneously with the Fe isotope exchange. The Fe-IE exponent on $T_c$ [$\alpha_{\rm Fe}=-(\Delta T_c/T_c)/(\Delta M/M)$, $M$ is the isotope mass] needs to be decomposed into two components with the one related to the structural changes ($\alpha_{\rm Fe}^{\rm str}$) and the genuine (intrinsic) one ($\alpha_{\rm Fe}^{\rm int}$). The validity of such decomposition is further confirmed by the fact that $\alpha_{\rm Fe}^{\rm int}$ coincides with the Fe-IE exponent on the characteristic phonon frequencies $\alpha_{\rm Fe}^{\rm ph}$ as is reported in recent EXAFS and Raman experiments.Comment: 7 pages, 4 figures. The paper is partially based on the results published in [New J. Phys. 12, 073024 (2010) = arXiv:1002.2510] and [Phys. Rev. B 82, 212505 (2010) = arXiv:1008.4540

Direct and indirect control of the initiation of meiotic recombination by DNA damage checkpoint mechanisms in budding yeast

Meiotic recombination plays an essential role in the proper segregation of chromosomes at meiosis I in many sexually reproducing organisms. Meiotic recombination is initiated by the scheduled formation of genome-wide DNA double-strand breaks (DSBs). The timing of DSB formation is strictly controlled because unscheduled DSB formation is detrimental to genome integrity. Here, we investigated the role of DNA damage checkpoint mechanisms in the control of meiotic DSB formation using budding yeast. By using recombination defective mutants in which meiotic DSBs are not repaired, the effect of DNA damage checkpoint mutations on DSB formation was evaluated. The Tel1 (ATM) pathway mainly responds to unresected DSB ends, thus the sae2 mutant background in which DSB ends remain intact was employed. On the other hand, the Mec1 (ATR) pathway is primarily used when DSB ends are resected, thus the rad51 dmc1 double mutant background was employed in which highly resected DSBs accumulate. In order to separate the effect caused by unscheduled cell cycle progression, which is often associated with DNA damage checkpoint defects, we also employed the ndt80 mutation which permanently arrests the meiotic cell cycle at prophase I. In the absence of Tel1, DSB formation was reduced in larger chromosomes (IV, VII, II and XI) whereas no significant reduction was found in smaller chromosomes (III and VI). On the other hand, the absence of Rad17 (a critical component of the ATR pathway) lead to an increase in DSB formation (chromosomes VII and II were tested). We propose that, within prophase I, the Tel1 pathway facilitates DSB formation, especially in bigger chromosomes, while the Mec1 pathway negatively regulates DSB formation. We also identified prophase I exit, which is under the control of the DNA damage checkpoint machinery, to be a critical event associated with down-regulating meiotic DSB formation

Adalimumab in Patients with Active Noninfectious Uveitis

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo

Modeling performance of Hadoop applications: A journey from queueing networks to stochastic well formed nets

Nowadays, many enterprises commit to the extraction of actionable knowledge from huge datasets as part of their core business activities. Applications belong to very different domains such as fraud detection or one-to-one marketing, and encompass business analytics and support to decision making in both private and public sectors. In these scenarios, a central place is held by the MapReduce framework and in particular its open source implementation, Apache Hadoop. In such environments, new challenges arise in the area of jobs performance prediction, with the needs to provide Service Level Agreement guarantees to the enduser and to avoid waste of computational resources. In this paper we provide performance analysis models to estimate MapReduce job execution times in Hadoop clusters governed by the YARN Capacity Scheduler. We propose models of increasing complexity and accuracy, ranging from queueing networks to stochastic well formed nets, able to estimate job performance under a number of scenarios of interest, including also unreliable resources. The accuracy of our models is evaluated by considering the TPC-DS industry benchmark running experiments on Amazon EC2 and the CINECA Italian supercomputing center. The results have shown that the average accuracy we can achieve is in the range 9–14%