On the Design and Development of Object-oriented Scheduling Systems

In this paper, we describe the architecture of an object-oriented scheduling system. First, a mathematical framework is presented that is based on set theory and graph theory. Then a number of basic as well as more specialized methods are defined which can be applied on the entities of any decision support system. The principal objects of a scheduling system are defined, as well as the methods specifically designed for the manipulation of the schedules. The object base design, the schedule generator design and the user interface design are then discussed in detail.Information Systems Working Papers Serie

Graph Transformation Based Guidance for Web Navigation

With growing information volume and diverse user preferences on the web, the performance of web information retrieval has become a critical issue. Web navigation is dramatically influenced by the organizations of web contents. Hence, useful navigation guidance can considerably accelerate the information retrieval process. In this paper, web navigation is formulated as a Directed Group Steiner Forest (DGSF) problem in line graph representation of the website. A heuristic algorithm is proposed to tackle the DGSF problem and attain the suboptimal solution in polynomial time. Simulations are conducted to compare the mean searching time for the proposed DGSF-based navigation guidance and other approaches. The results suggest that the DGSF-based navigation guidance can significantly reduce the mean searching time, especially when the number of web pages is large while the number of destination pages is moderate. The discussion is also made for extending the model to take into account the websites owner’s interests and other concerns as well

Automatic Fall Risk Detection based on Imbalanced Data

In recent years, the declining birthrate and aging population have gradually brought countries into an ageing society. Regarding accidents that occur amongst the elderly, falls are an essential problem that quickly causes indirect physical loss. In this paper, we propose a pose estimation-based fall detection algorithm to detect fall risks. We use body ratio, acceleration and deflection as key features instead of using the body keypoints coordinates. Since fall data is rare in real-world situations, we train and evaluate our approach in a highly imbalanced data setting. We assess not only different imbalanced data handling methods but also different machine learning algorithms. After oversampling on our training data, the K-Nearest Neighbors (KNN) algorithm achieves the best performance. The F1 scores for three different classes, Normal, Fall, and Lying, are 1.00, 0.85 and 0.96, which is comparable to previous research. The experiment shows that our approach is more interpretable with the key feature from skeleton information. Moreover, it can apply in multi-people scenarios and has robustness on medium occlusion

On the Design and Development of Object-oriented Scheduling Systems

In this paper, we describe the architecture of an object-oriented scheduling system. First, a mathematical framework is presented that is based on set theory and graph theory. Then a number of basic as well as more specialized methods are defined which can be applied on the entities of any decision support system. The principal objects of a scheduling system are defined, as well as the methods specifically designed for the manipulation of the schedules. The object base design, the schedule generator design and the user interface design are then discussed in detail.Information Systems Working Papers Serie

Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion

Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication

Single-dose pharmacokinetic and toxicity analysis of pyrrole–imidazole polyamides in mice

Purpose: Pyrrole–imidazole (Py-Im) polyamides are programmable, sequence-specific DNA minor groove–binding ligands. Previous work in cell culture has shown that various polyamides can be used to modulate the transcriptional programs of oncogenic transcription factors. In this study, two hairpin polyamides with demonstrated activity against androgen receptor signaling in cell culture were administered to mice to characterize their pharmacokinetic properties. Methods: Py-Im polyamides were administered intravenously by tail vein injection. Plasma, urine, and fecal samples were collected over a 24-h period. Liver, kidney, and lung samples were collected postmortem. Concentrations of the administered polyamide in the plasma, excretion, and tissue samples were measured using LC/MS/MS. The biodistribution data were analyzed by both non-compartmental and compartmental pharmacokinetic models. Animal toxicity experiments were also performed by monitoring weight loss after a single subcutaneous (SC) injection of either polyamide. Results: The biodistribution profiles of both compounds exhibited rapid localization to the liver, kidneys, and lungs upon injection. Plasma distribution of the two compounds showed distinct differences in the rate of clearance, the volume of distribution, and the AUCs. These two compounds also have markedly different toxicities after SC injection in mice. Conclusions: The variations in pharmacokinetics and toxicity in vivo stem from a minor chemical modification that is also correlated with differing potency in cell culture. The results obtained in this study could provide a structural basis for further improvement of polyamide activity both in cell culture and in animal models

Characterization of hemin-binding protein 35 (HBP35) in Porphyromonas gingivalis: its cellular distribution, thioredoxin activity and role in heme utilization

<p>Abstract</p> <p>Background</p> <p>The periodontal pathogen <it>Porphyromonas gingivalis </it>is an obligate anaerobe that requires heme for growth. To understand its heme acquisition mechanism, we focused on a hemin-binding protein (HBP35 protein), possessing one thioredoxin-like motif and a conserved C-terminal domain, which are proposed to be involved in redox regulation and cell surface attachment, respectively.</p> <p>Results</p> <p>We observed that the <it>hbp35 </it>gene was transcribed as a 1.1-kb mRNA with subsequent translation resulting in three proteins with molecular masses of 40, 29 and 27 kDa in the cytoplasm, and one modified form of the 40-kDa protein on the cell surface. A recombinant 40-kDa HBP35 exhibited thioredoxin activity <it>in vitro </it>and mutation of the two putative active site cysteine residues abolished this activity. Both recombinant 40- and 27-kDa proteins had the ability to bind hemin, and growth of an <it>hbp35 </it>deletion mutant was substantially retarded under hemin-depleted conditions compared with growth of the wild type under the same conditions.</p> <p>Conclusion</p> <p><it>P. gingivalis </it>HBP35 exhibits thioredoxin and hemin-binding activities and is essential for growth in hemin-depleted conditions suggesting that the protein plays a significant role in hemin acquisition.</p

Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty.

Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (−2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate wit

Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

Red blood cell tension protects against severe malaria in the Dantu blood group.

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.JCR, AM and DK were supported by the Wellcome Trust (206194/Z/17/Z). MPW is funded by a Wellcome Senior Fellowship (108070). TNW is funded through Fellowships awarded by the Wellcome Trust (091758 and 202800). SNK is supported by the Wellcome Trust-funded Initiative to Develop African Research Leaders (IDeAL) early-career postdoctoral fellowship (107769/Z/10/Z), supported through the DELTAS Africa Initiative (DEL-15-003). The Wellcome Trust provides core support to The KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya (084535), Wellcome Sanger Institute, Cambridge, UK (206194/Z/17/Z) and the Wellcome Centre for Human Genetics, Oxford, UK (090532/Z/09/Z, 203141). PC is supported by the Engineering and Physical Sciences Research Council (EPSRC) (EP/R011443/1), and VI is supported by the EPSRC and the Sackler fellowship