A Method for Solving a Class of Multiple-Criteria Analysis Problems

AMS subject classification: 90C29.The paper proposes an interactive method solving the multiple criteria choice problem (MCCP) with a large number of discrete alternatives and a small number of quantitative criteria. The decision maker (DM) sets his preferences in terms of desired directions of improving or relaxing of the criteria. On this base the so called reference cone is constructed. A small subset of relatively closed alternatives is defined according to this cone and to the maximal deterioration of the criteria values at each iteration. This subset is evaluated by the DM, who selects the most preferred alternative or enters his/her new preferences. The method suggested has user-friendly dialog. It enables the DM to explore the set of alternatives comparatively quickly and easy. The method is included in a DSS. It is tested by a number of real multiple criteria choice problems

Identification of genes that are essential to restrict genome duplication to once per cell division.

Nuclear genome duplication is normally restricted to once per cell division, but aberrant events that allow excess DNA replication (EDR) promote genomic instability and aneuploidy, both of which are characteristics of cancer development. Here we provide the first comprehensive identification of genes that are essential to restrict genome duplication to once per cell division. An siRNA library of 21,584 human genes was screened for those that prevent EDR in cancer cells with undetectable chromosomal instability. Candidates were validated by testing multiple siRNAs and chemical inhibitors on both TP53+ and TP53- cells to reveal the relevance of this ubiquitous tumor suppressor to preventing EDR, and in the presence of an apoptosis inhibitor to reveal the full extent of EDR. The results revealed 42 genes that prevented either DNA re-replication or unscheduled endoreplication. All of them participate in one or more of eight cell cycle events. Seventeen of them have not been identified previously in this capacity. Remarkably, 14 of the 42 genes have been shown to prevent aneuploidy in mice. Moreover, suppressing a gene that prevents EDR increased the ability of the chemotherapeutic drug Paclitaxel to induce EDR, suggesting new opportunities for synthetic lethalities in the treatment of human cancers

Keystroke dynamics using auto encoders

In the modern day and age, credential based authentication systems no longer provide the level of security that many organisations and their services require. The level of trust in passwords has plummeted in recent years, with waves of cyber attacks predicated on compromised and stolen credentials. This method of authentication is also heavily reliant on the individual user’s choice of password. There is the potential to build levels of security on top of credential based authentication systems, using a risk based approach, which preserves the seamless authentication experience for the end user. One method of adding this security to a risk based authentication framework, is keystroke dynamics. Monitoring the behaviour of the users and how they type, produces a type of digital signature which is unique to that individual. Learning this behaviour allows dynamic flags to be applied to anomalous typing patterns that are produced by attackers using stolen credentials, as a potential risk of fraud. Methods from statistics and machine learning have been explored to try and implement such solutions. This paper will look at an Autoencoder model for learning the keystroke dynamics of specific users. The results from this paper show an improvement over the traditional tried and tested statistical approaches with an Equal Error Rate of 6.51%, with the additional benefits of relatively low training times and less reliance on feature engineering

Mortality of patients with multiple sclerosis: a cohort study in UK primary care

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001–2006 and validated using patients’ original records where possible. We also included MS cases during 1993–2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4–2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46–2.38) vs. HR 1.31 (95 % CI 0.93–1.84), respectively. The most commonly recorded cause of death in MS patients was ‘MS’ (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients. Electronic supplementary material The online version of this article (doi:10.1007/s00415-014-7370-3) contains supplementary material, which is available to authorized users

Modifiable risk factors for dementia, and awareness of brain health behaviors: Results from the Five Lives Brain Health Ireland Survey (FLBHIS)

Up to 40% of dementias globally are attributable to modifiable risk factors. Many existing studies examining attitudes to brain health are limited by a failure to consider a range of pertinent risk factors and associated barriers to protective behaviors. In Ireland, self-reported knowledge of dementia is poor compared to other conditions. In this context, the current study aimed to explore exposure to and awareness of specific modifiable risk factors for dementia. We also aimed to investigate whether exposure to these risk factors is associated with demographic and socioeconomic factors. A cross-sectional survey was administered to 555 voluntary participants in February 2022. The survey captured the following information: (1) Sociodemographic factors; (2) Exposure to, as well as knowledge of modifiable risk factors for dementia, namely diet, social interaction, exercise, hypertension, sleep, depression, smoking, alcohol consumption, cognitive stimulation, hearing impairment, diabetes, air pollution, and head injury. The study population comprised 551 participants (50.3% male; 49.6% female). Mean age was 59.7 years. Modifiable risk factors for dementia were prevalent. Relative to females, male gender was significantly associated with multiple risk factors. Whilst 65.6% of participants believed that lifestyle improvements can decrease a person’s risk of developing dementia, only 31.4% believed that dementia could be prevented. Head injury (90.9%, n = 500), low mental stimulation (85.3%, n = 469), and alcohol consumption (77.8%, n = 428) were the three most commonly recognized risk factors. Awareness was significantly greater in both university groups (undergraduate and postgraduate) for multiple risk factors. Our findings demonstrate that the distribution of exposure to modifiable risk factors for dementia is unequal across gender and age groups, and that awareness levels vary across risk factors. These findings highlight that focus surrounding dementia prevention should shift toward individual risk profiling and should be tailored toward an individual’s specific needs

Flux-free conductance modulation in a helical Aharonov-Bohm interferometer

A novel conductance oscillation in a twisted quantum ring composed of a helical atomic configuration is theoretically predicted. Internal torsion of the ring is found to cause a quantum phase shift in the wavefunction that describes the electron's motion along the ring. The resulting conductance oscillation is free from magnetic flux penetrating inside the ring, which is in complete contrast with the ordinary Aharonov-Bohm effect observed in untwisted quantum rings.Comment: 10 pages, 4 figure

Risk assessment of non-native fishes in the Balkans Region using FISK, the invasiveness screening tool for non-native freshwater fishes

A high level of freshwater fish endemism in the Balkans Region emphasizes the need for non-native species risk assessments to inform management and control measures, with pre-screening tools, such as the Fish Invasiveness Screening Kit (FISK) providing a useful first step. Applied to 43 non-native and translocated freshwater fishes in four Balkan countries, FISK reliably discriminated between invasive and non-invasive species, with a calibration threshold value of 9.5 distinguishing between species of medium and high risk sensu lato of becoming invasive. Twelve of the 43 species were assessed by scientists from two or more Balkan countries, and the remaining 31 species by a single assessor. Using the 9.5 threshold, three species were classed as low risk, 10 as medium risk, and 30 as high risk, with the latter category comprised of 26 moderately high risk, three high risk, and one very high risk species. Confidence levels in the assessments were relatively constant for all species, indicating concordance amongst assessors

O18O and C18O observations of rho Oph A

Observations of the (N_J=1_1-1_0) ground state transition of O_2 with the Odin satellite resulted in a about 5 sigma detection toward the dense core rho Oph A. At the frequency of the line, 119 GHz, the Odin telescope has a beam width of 10', larger than the size of the dense core, so that the precise nature of the emitting source and its exact location and extent are unknown. The current investigation is intended to remedy this. Telluric absorption makes ground based O_2 observations essentially impossible and observations had to be done from space. mm-wave telescopes on space platforms were necessarily small, which resulted in large, several arcminutes wide, beam patterns. Although the Earth's atmosphere is entirely opaque to low-lying O_2 transitions, it allows ground based observations of the much rarer O18O in favourable conditions and at much higher angular resolution with larger telescopes. In addition, rho Oph A exhibits both multiple radial velocity systems and considerable velocity gradients. Extensive mapping of the region in the proxy C18O (J=3-2) line can be expected to help identify the O_2 source on the basis of its line shape and Doppler velocity. Line opacities were determined from observations of optically thin 13C18O (J=3-2) at selected positions. During several observing periods, two C18O intensity maxima in rho Oph A were searched for in the 16O18O (2_1-0_1) line at 234 GHz with the 12m APEX telescope. Our observations resulted in an upper limit on the integrated O18O intensity of < 0.01 K km/s (3 sigma) into the 26.5" beam. We conclude that the source of observed O_2 emission is most likely confined to the central regions of the rho Oph A cloud. In this limited area, implied O_2 abundances could thus be higher than previously reported, by up to two orders of magnitude.Comment: 7 pages, 6 figures (5 colour), Astronomy & Astrophysic

Selective elimination of pluripotent stem cells by PIKfyve specific inhibitors.

Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their ability to form teratocarcinomas in mice, and intraperitoneal injections of WX8 into mice harboring teratocarcinoma xenografts selectively eliminated pluripotent cells. Differentiated cells continued to proliferate, but at a reduced rate. These results provide a proof of principle that PIKfyve specific inhibitors can selectively eliminate pluripotent stem cells in vivo as well as in vitro