The parameterized complexity of some geometric problems in unbounded dimension

We study the parameterized complexity of the following fundamental geometric problems with respect to the dimension $d$: i) Given $n$ points in \Rd, compute their minimum enclosing cylinder. ii) Given two $n$-point sets in \Rd, decide whether they can be separated by two hyperplanes. iii) Given a system of $n$ linear inequalities with $d$ variables, find a maximum-size feasible subsystem. We show that (the decision versions of) all these problems are W[1]-hard when parameterized by the dimension $d$. %and hence not solvable in ${O}(f(d)n^c)$ time, for any computable function $f$ and constant $c$ %(unless FPT=W[1]). Our reductions also give a $n^{\Omega(d)}$-time lower bound (under the Exponential Time Hypothesis)

Earthquake networks based on similar activity patterns

Earthquakes are a complex spatiotemporal phenomenon, the underlying mechanism for which is still not fully understood despite decades of research and analysis. We propose and develop a network approach to earthquake events. In this network, a node represents a spatial location while a link between two nodes represents similar activity patterns in the two different locations. The strength of a link is proportional to the strength of the cross-correlation in activities of two nodes joined by the link. We apply our network approach to a Japanese earthquake catalog spanning the 14-year period 1985-1998. We find strong links representing large correlations between patterns in locations separated by more than 1000 km, corroborating prior observations that earthquake interactions have no characteristic length scale. We find network characteristics not attributable to chance alone, including a large number of network links, high node assortativity, and strong stability over time.Comment: 8 pages text, 9 figures. Updated from previous versio

PReS-FINAL-2161: Safety and effectiveness of adalimumab in children with polyarticular juvenile idiopathic arthritis aged 2 to <4 years or >=4 years weighing <15 kg

International audienceEn faisant le tour du monde (Mauritanie, Madagascar, Éthiopie, Burkina Faso, Cameroun, New-York, Nouvelle-Zélande, France... ) en passant par l’Internet, cet ouvrage fait le point sur les dernières innovations en matière de gestion des déchets. Considéré comme une ressource, le déchet révèle enfin sa valeur : il est créateur de revenus, de liens sociaux et de nouvelles technologies. C’est pourquoi il devient urgent de structurer son économie

Interprofessional Communication of Clinicians Using a Mobile Phone App: A Randomized Crossover Trial Using Simulated Patients

Background: Most hospitals use paging systems as the principal communication system, despite general dissatisfaction by end users. To this end, we developed an app-based communication system (called Hark) to facilitate and improve the quality of interpersonal communication. Objective: The objectives of our study were (1) to assess the quality of information transfer using pager- and app-based (Hark) communication systems, (2) to determine whether using mobile phone apps for escalation of care results in additional delays in communication, and (3) to determine how end users perceive mobile phone apps as an alternative to pagers. Methods: We recruited junior (postgraduate year 1 and 2) doctors and nurses from a range of specialties and randomly assigned them to 2 groups who used either a pager device or the mobile phone-based Hark app. We asked nurses to hand off simulated patients while doctors were asked to receive handoff information using these devices. The quality of information transfer, time taken to respond to messages, and users’ satisfaction with each device was recorded. Each participant used both devices with a 2-week washout period in between uses. Results: We recruited 22 participants (13 nurses, 9 doctors). The quality of the referrals made by nurses was significantly better when using Hark (Hark median 118, range 100–121 versus pager median 77, range 39–104; P=.001). Doctors responded to messages using Hark more quickly than when responding to pagers, although this difference was not statistically significant (Hark mean 86.6 seconds, SD 96.2 versus pager mean 136.5 seconds, SD 201.0; P=.12). Users rated Hark as significantly better on 11 of the 18 criteria of an information transfer device (P<.05) These included “enhances interprofessional efficiency,” “results in less disturbance,” “performed desired functions reliably,” and “allows me to clearly transfer information.” Conclusions: Hark improved the quality of transfer of information about simulated patients and was rated by users as more effective and efficient, and less distracting than pagers. Using this device did not result in delay in patient care

Fast by Nature - How Stress Patterns Define Human Experience and Performance in Dexterous Tasks

In the present study we quantify stress by measuring transient perspiratory responses on the perinasal area through thermal imaging. These responses prove to be sympathetically driven and hence, a likely indicator of stress processes in the brain. Armed with the unobtrusive measurement methodology we developed, we were able to monitor stress responses in the context of surgical training, the quintessence of human dexterity. We show that in dexterous tasking under critical conditions, novices attempt to perform a task's step equally fast with experienced individuals. We further show that while fast behavior in experienced individuals is afforded by skill, fast behavior in novices is likely instigated by high stress levels, at the expense of accuracy. Humans avoid adjusting speed to skill and rather grow their skill to a predetermined speed level, likely defined by neurophysiological latency

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy

BRCA1, a key factor in homologous recombination repair may also regulate base excision repair (BER). Targeting BRCA1-BER deficient cells by blockade of ATM and DNA-PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1 and pol β protein expression in two cohorts (n=1602 sporadic and n=50 germ-line BRCA1 mutated) and mRNA expression in two cohorts (n=1952 and n=249). Artificial neural network analysis for BRCA1-DNA repair interacting genes was conducted in 249 tumours. Pre-clinically, BRCA1 proficient and deficient cells were DNA repair expression profiled and evaluated for synthetic lethality using ATM and DNA-PKcs inhibitors either alone or in combination with cisplatin. In human tumours, BRCA1 negativity was strongly associated with low XRCC1, and low pol β at mRNA and protein levels (p<0.0001). In patients with BRCA1 negative tumours, low XRCC1 or low pol β expression was significantly associated with poor survival in univariate and multivariate analysis compared to high XRCC1 or high pol β expressing BRCA1 negative tumours (ps<0.05). Pre-clinically, BRCA1 negative cancer cells exhibit low mRNA and low protein expression of XRCC1 and pol β. BRCA1-BER deficient cells were sensitive to ATM and DNA-PKcs inhibitor treatment either alone or in combination with cisplatin and synthetic lethality was evidenced by DNA double strand breaks accumulation, cell cycle arrest and apoptosis. We conclude that XRCC1 and pol β expression status in BRCA1 negative tumours may have prognostic significance. BRCA1-BER deficient cells could be targeted by ATM or DNA-PKcs inhibitors for personalized therapy

Generalized Drude model: Unification of ballistic and diffusive electron transport

For electron transport in parallel-plane semiconducting structures, a model is developed that unifies ballistic and diffusive transport and thus generalizes the Drude model. The unified model is valid for arbitrary magnitude of the mean free path and arbitrary shape of the conduction band edge profile. Universal formulas are obtained for the current-voltage characteristic in the nondegenerate case and for the zero-bias conductance in the degenerate case, which describe in a transparent manner the interplay of ballistic and diffusive transport. The semiclassical approach is adopted, but quantum corrections allowing for tunneling are included. Examples are considered, in particular the case of chains of grains in polycrystalline or microcrystalline semiconductors with grain size comparable to, or smaller than, the mean free path. Substantial deviations of the results of the unified model from those of the ballistic thermionic-emission model and of the drift-diffusion model are found. The formulation of the model is one-dimensional, but it is argued that its results should not differ substantially from those of a fully three-dimensional treatment.Comment: 14 pages, 5 figures, REVTEX file, to appear in J. Phys.: Condens. Matte

A Matrix Hyperbolic Cosine Algorithm and Applications

In this paper, we generalize Spencer's hyperbolic cosine algorithm to the matrix-valued setting. We apply the proposed algorithm to several problems by analyzing its computational efficiency under two special cases of matrices; one in which the matrices have a group structure and an other in which they have rank-one. As an application of the former case, we present a deterministic algorithm that, given the multiplication table of a finite group of size $n$, it constructs an expanding Cayley graph of logarithmic degree in near-optimal O(n^2 log^3 n) time. For the latter case, we present a fast deterministic algorithm for spectral sparsification of positive semi-definite matrices, which implies an improved deterministic algorithm for spectral graph sparsification of dense graphs. In addition, we give an elementary connection between spectral sparsification of positive semi-definite matrices and element-wise matrix sparsification. As a consequence, we obtain improved element-wise sparsification algorithms for diagonally dominant-like matrices.Comment: 16 pages, simplified proof and corrected acknowledging of prior work in (current) Section

Potentiation of PBD Dimers by Lipophilicity Manipulation

Background & Introduction: Pyrrolobenzodiazepine (PBD) dimers are highly potent DNA cross-linking agents used as warheads in Antibody Drug Conjugates (ADCs) for cancer therapy. We propose to investigate the correlation existing between the lipophilicity of those molecules and their activity (both in vitro and in vivo) as well as any effect observed during conjugation. / Materials and Methods: Reaction progress was monitored by Thin-Layer Chromatography (TLC) using Merck Kieselgel 60 F254 silica gel, with a fluorescent indicator on aluminium plates. Visualisation of TLC was achieved with UV light or iodine vapour unless otherwise stated. Flash chromatography was performed using Merck Kieselgel 60 F254 silica gel. / Results: We have successfully designed and synthesized a novel PBD warhead (SG3312) with enhanced physicochemical properties. The warhead also displayed increased potency in vitro. After overcoming some epimerization issues, the synthesis of enantiomerically pure payload was achieved (SG3259) and fulfilled our criteria for a simplified and more efficient conjugation. No addition of propylene glycol was required, and high DAR and excellent monomeric purity were achieved. / Conclusion: The ADC (Herceptin-maia-SG3259) has been shown to release the active warhead (SG3312) upon exposure to Cathepsin B and demonstrated encouraging activity both in vitro and in vivo