Estimating attraction basin sizes

The performance of local search algorithms is influenced by the properties that the neighborhood imposes on the search space. Among these properties, the number of local optima has been traditionally considered as a complexity measure of the instance, and different methods for its estimation have been developed. The accuracy of these estimators depends on properties such as the relative attraction basin sizes. As calculating the exact attraction basin sizes becomes unaffordable for moderate problem sizes, their estimations are required. The lack of techniques achieving this purpose encourages us to propose two methods that estimate the attraction basin size of a given local optimum. The first method takes uniformly at random solutions from the whole search space, while the second one takes into account the structure defined by the neighborhood. They are tested on different instances of problems in the permutation space, considering the swap and the adjacent swap neighborhoods

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

High Amplitude Phase Resetting in Rev-Erbα/Per1 Double Mutant Mice

Over time, organisms developed various strategies to adapt to their environment. Circadian clocks are thought to have evolved to adjust to the predictable rhythms of the light-dark cycle caused by the rotation of the Earth around its own axis. The rhythms these clocks generate persist even in the absence of environmental cues with a period of about 24 hours. To tick in time, they continuously synchronize themselves to the prevailing photoperiod by appropriate phase shifts. In this study, we disrupted two molecular components of the mammalian circadian oscillator, Rev-Erbα and Period1 (Per1). We found that mice lacking these genes displayed robust circadian rhythms with significantly shorter periods under constant darkness conditions. Strikingly, they showed high amplitude resetting in response to a brief light pulse at the end of their subjective night phase, which is rare in mammals. Surprisingly, Cry1, a clock component not inducible by light in mammals, became slightly inducible in these mice. Taken together, Rev-Erbα and Per1 may be part of a mechanism preventing drastic phase shifts in mammals

Is standard breast-conserving therapy (BCT) in elderly breast cancer patients justified? A prospective measurement of acute toxicity according CTC-classification

<p>Abstract</p> <p>Background</p> <p>Breast conserving therapy (BCT) is an accepted treatment for early-stage breast cancer. This study aimed to measure prospectively acute radiation-related toxicity and to create a comprehensive data base for long-term temporal analyses of 3D conformal adjuvant radiotherapy. The specific aspect of age has been neglected by traditional research. Therefore, the impact of age on acute BCT toxicity should be also specifically adressed.</p> <p>Methods</p> <p>Toxicity was measured in 109 patients at initiation (t1), during radiotherapy (t2-t7), and 6 weeks after treatment completion (t8) using a new topographic module. Organ systems were recorded in 15 scales and scored according to symptom intensity (grade 0-5) based on CTC (Common Toxicity Criteria) -classification. Radiotherapy was virtually CT-based planned and applied with 6-MeV-photons. Mean total dose was 60.1 Gy. Patients were stratified by age in 3 Groups: <50, 50-60, and >60 years.</p> <p>Results</p> <p>Registered toxicity was generally low. Mean overall-grade climbed from 0.29-0.40 (t1-t7), and dropped to 0.23 (t8). Univariate analyses revealed slightly higher toxicity in older (> 60 years) versus young patients (< 50 years) in 2 scales only: breast-symmetry (p = 0.033), and arm function (p = 0.007). However, in the scale "appetite" toxicity was higher in younger (< 50 years) versus older (> 60 years) patients (p = 0.039). Toxicity differences in all other scales were not significant. Between older (> 60 years) and midaged patients (50-60 years) no significant differences in toxicity were found. This was also true for the comparison between young (< 50 years) versus midaged patient groups (50-60 years).</p> <p>Conclusion</p> <p>The treatment concept of BCT for breast cancer is generally well tolerated. The toxicity-measurement with the new topographic module is feasible. Not modified standard treatment for BC should be performed in elderly women.</p

Resonant Zener tunnelling via zero-dimensional states in a narrow gap diode

Interband tunnelling of carriers through a forbidden energy gap, known as Zener tunnelling, is a phenomenon of fundamental and technological interest. Its experimental observation in the Esaki p-n semiconductor diode has led to the first demonstration and exploitation of quantum tunnelling in a condensed matter system. Here we demonstrate a new type of Zener tunnelling that involves the resonant transmission of electrons through zero-dimensional (0D) states. In our devices, a narrow quantum well of the mid-infrared (MIR) alloy In(AsN) is placed in the intrinsic (i) layer of a p-i-n diode. The incorporation of nitrogen in the quantum well creates 0D states that are localized on nanometer lengthscales. These levels provide intermediate states that act as “stepping stones” for electrons tunnelling across the diode and give rise to a negative differential resistance (NDR) that is weakly dependent on temperature. These electron transport properties have potential for the development of nanometre-scale non-linear components for electronics and MIR photonics

How much time do health services spend on antenatal care? Implications for the introduction of the focused antenatal care model in Tanzania

BACKGROUND: Antenatal care (ANC) is a widely used strategy to improve the health of pregnant women and to encourage skilled care during childbirth. In 2002, the Ministry of Health of the United Republic of Tanzania developed a national adaptation plan based on the new model of the World Health Organisation (WHO). In this study we assess the time health workers currently spent on providing ANC services and compare it to the requirements anticipated for the new ANC model in order to identify the implications of Focused ANC on health care providers' workload. METHODS: Health workers in four dispensaries in Mtwara Urban District, Southern Tanzania, were observed while providing routine ANC. The time used for the overall activity as well as for the different, specific components of 71 ANC service provisions was measured in detail; 28 of these were first visits and 43 revisits. Standard time requirements for the provision of focused ANC were assessed through simulated consultations based on the new guidelines. RESULTS: The average time health workers currently spend for providing ANC service to a first visit client was found to be 15 minutes; the provision of ANC according to the focused ANC model was assessed to be 46 minutes. For a revisiting client the difference between current practise and the anticipated standard of the new model was 27 minutes (9 vs. 36 min.). The major discrepancy between the two procedures was related to counselling. On average a first visit client was counselled for 1:30 minutes, while counselling in revisiting clients did hardly take place at all. The simulation of focused ANC revealed that proper counselling would take about 15 minutes per visit. CONCLUSION: While the introduction of focused ANC has the potential to improve the health of pregnant women and to raise the number of births attended by skilled staff in Tanzania, it may need additional investment in human resources. The generally anticipated saving effect of the new model through the reduction of routine consultations may not materialise because the number of consultations is already low in Tanzania with a median of only 4 visits per pregnancy. Special attention needs to be given to counselling attitudes and skills during the training for Focused ANC as this component is identified as the major difference between old practise and the new model. Our estimated requirement of 46 minutes per first visit consultation matches well with the WHO estimate of 40 minutes

The influence of spatial pattern on visual short-term memory for contrast

Several psychophysical studies of visual short-term memory (VSTM) have shown high-fidelity storage capacity for many properties of visual stimuli. On judgments of the spatial frequency of gratings, for example, discrimination performance does not decrease significantly, even for memory intervals of up to 30 s. For other properties, such as stimulus orientation and contrast, however, such “perfect storage” behavior is not found, although the reasons for this difference remain unresolved. Here, we report two experiments in which we investigated the nature of the representation of stimulus contrast in VSTM using spatially complex, two-dimensional random-noise stimuli. We addressed whether information about contrast per se is retained during the memory interval by using a test stimulus with the same spatial structure but either the same or the opposite local contrast polarity, with respect to the comparison (i.e., remembered) stimulus. We found that discrimination thresholds got steadily worse with increasing duration of the memory interval. Furthermore, performance was better when the test and comparison stimuli had the same local contrast polarity than when they were contrast-reversed. Finally, when a noise mask was introduced during the memory interval, its disruptive effect was maximal when the spatial configuration of its constituent elements was uncorrelated with those of the comparison and test stimuli. These results suggest that VSTMfor contrast is closely tied to the spatial configuration of stimuli and is not transformed into a more abstract representation

Interactions of polymorphisms in different clock genes associated with circadian phenotypes in humans

Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1) in people with extreme diurnal preferences (morning or evening). We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology

Assessing the Feasibility of Single Trace Power Analysis of Frodo

Lattice-based schemes are among the most promising post-quantum schemes, yet the effect of both parameter and implementation choices on their side-channel resilience is still poorly understood. Aysu et al. (HOST\u2718) recently investigated single-trace attacks against the core lattice operation, namely multiplication between a public matrix and a small secret vector, in the context of a hardware implementation. We complement this work by considering single-trace attacks against software implementations of ring-less LWE-based constructions. Specifically, we target Frodo, one of the submissions to the standardisation process of NIST, when implemented on an (emulated) ARM Cortex M0 processor. We confirm Aysu et al.\u27s observation that a standard divide-and-conquer attack is insufficient and instead we resort to a sequential, extend-and-prune approach. In contrast to Aysu et al. we find that, in our setting where the power model is far from being as clear as theirs, both profiling and less aggressive pruning are needed to obtain reasonable key recovery rates for SNRs of practical relevance. Our work drives home the message that parameter selection for LWE schemes is a double-edged sword: the schemes that are deemed most secure against (black-box) lattice attacks can provide the least security when considering side-channels. Finally, we suggest some easy countermeasures that thwart standard extend-and-prune attacks