Quantum Optimization Problems

Krentel [J. Comput. System. Sci., 36, pp.490--509] presented a framework for an NP optimization problem that searches an optimal value among exponentially-many outcomes of polynomial-time computations. This paper expands his framework to a quantum optimization problem using polynomial-time quantum computations and introduces the notion of an ``universal'' quantum optimization problem similar to a classical ``complete'' optimization problem. We exhibit a canonical quantum optimization problem that is universal for the class of polynomial-time quantum optimization problems. We show in a certain relativized world that all quantum optimization problems cannot be approximated closely by quantum polynomial-time computations. We also study the complexity of quantum optimization problems in connection to well-known complexity classes.Comment: date change

Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects

The human sodium channel family includes seven neuronal channels that are essential for the initiation and propagation of action potentials in the CNS and PNS. In view of their critical role in neuronal firing and their strong sequence conservation during evolution, it is not surprising that mutations in the sodium channel genes are responsible for a growing spectrum of channelopathies. Nearly 700 mutations of the SCN1A gene have been identified in patients with Dravet's syndrome (severe myoclonic epilepsy of infancy), making this the most commonly mutated gene in human epilepsy. A small number of mutations have been found in SCN2A , SCN3A and SCN9A , and studies in the mouse suggest that SCN8A may also contribute to seizure disorders. Interactions between genetic variants of SCN2A and KCNQ2 in the mouse and variants of SCN1A and SCN9A in patients provide models of potential genetic modifier effects in the more common human polygenic epilepsies. New methods for generating induced pluripotent stem cells and neurons from patients will facilitate functional analysis of amino acid substitutions in channel proteins. Whole genome sequencing and exome sequencing in patients with epilepsy will soon make it possible to detect multiple variants and their interactions in the genomes of patients with seizure disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79388/1/jphysiol.2010.188482.pd

Essential Factors for Incompatible DNA End Joining at Chromosomal DNA Double Strand Breaks In Vivo

Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double strand break (DSBs) with incompatible DNA ends, which are often generated by ionizing irradiation. In vitro reconstitution studies have indicated that NHEJ of incompatible DNA ends requires not only the core steps of synapsis and ligation, employing KU80/DNA-PKcs and LIG4, but also additional DNA end processing steps, such as DNA end resection by Artemis and gap-filling by POLλ and POLμ. It seems that DNA end processing steps are important for joining of incompatible DNA ends rather than compatible ends. Despite the fact that DNA end processing is important for incompatible DNA end joining in vitro, the role of DNA processing in NHEJ of incompatible DSBs in vivo has not yet been demonstrated. Here we investigated the in vivo roles of proteins implicated in each step of NHEJ using an assay in which NHEJ of incompatible DNA ends on chromosomal DNA can be assessed in living human cells. siRNA- or inhibitor-mediated impairment of factors in each NHEJ step resulted in a reduction in joining efficiency. Strikingly, stronger effects were observed when DNA end resection and ligation protein functions were impaired. Disruption of synapsis by KU80 and DNA-PKcs impairment, or the disruption of gap filling by POLλ and POLμ depletion, resulted in higher levels of microhomology-mediated joining. The present study indicates that DNA end resection and ligation factors are critical for the efficient joining of incompatible ends in vivo, further emphasizing the importance of synapsis and gap-filling factors in preventing illegitimate joining

Identification of lung cancer with high sensitivity and specificity by blood testing

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a very frequent and lethal tumor with an identifiable risk population. Cytological analysis and chest X-ray failed to reduce mortality, and CT screenings are still controversially discussed. Recent studies provided first evidence for the potential usefulness of autoantigens as markers for lung cancer.</p> <p>Methods</p> <p>We used extended panels of arrayed antigens and determined autoantibody signatures of sera from patients with different kinds of lung cancer, different common non-tumor lung pathologies, and controls without any lung disease by a newly developed computer aided image analysis procedure. The resulting signatures were classified using linear kernel Support Vector Machines and 10-fold cross-validation.</p> <p>Results</p> <p>The novel approach allowed for discriminating lung cancer patients from controls without any lung disease with a specificity of 97.0%, a sensitivity of 97.9%, and an accuracy of 97.6%. The classification of stage IA/IB tumors and controls yielded a specificity of 97.6%, a sensitivity of 75.9%, and an accuracy of 92.9%. The discrimination of lung cancer patients from patients with non-tumor lung pathologies reached an accuracy of 88.5%.</p> <p>Conclusion</p> <p>We were able to separate lung cancer patients from subjects without any lung disease with high accuracy. Furthermore, lung cancer patients could be seprated from patients with other non-tumor lung diseases. These results provide clear evidence that blood-based tests open new avenues for the early diagnosis of lung cancer.</p

Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death

Replication Factor C Complexes Play Unique Pro- and Anti-Establishment Roles in Sister Chromatid Cohesion

Recent studies have lead to a rapid expansion of sister chromatid cohesion pathways. Of particular interest is the growth in classifications of anti-establishment factors—now including those that are cohesin-associated (Rad61/WAPL and Pds5) or DNA replication fork-associated (Elg1-RFC). In this study, we show that the two classes of anti-establishment complexes are indistinguishable when challenged both genetically and functionally. These findings suggest that both classes function in a singular pathway that is centered on Ctf7/Eco1 (herein termed Ctf7) regulation. The anti-establishment activity of Elg1-RFC complex is particular intriguing given that an alternate Ctf18-RFC complex exhibits robust pro-establishment activity. Here, we provide several lines of evidence, including the use of Ctf7 bypass suppressors, indicating that these activities are not simply antagonistic. Moreover, the results suggest that Ctf18-RFC is capable of promoting sister chromatid pairing reactions independent of Ctf7. The combination of these studies suggest a new model of sister chromatid pairing regulation

Burnout syndrome in Cypriot physiotherapists: a national survey

Background. Burnout in the healthcare workers is formally defined as a state of physical, emotional and mental exhaustion caused by long-term involvement in situations that are emotionally demanding. Methods. Using a random stratified sampling method and taking into account geographical location, specialty and type of employment, 172 physiotherapists working both in the private and public sectors completed an anonymous questionnaire that included several aspects related to burnout; the MBI scale, questions related to occupational stress, and questions pertaining to self image. Results. Almost half (46%) of the 172 participants believed that their job is stressful. Approximately 57% of the physiotherapists who worked in the public sector and 40% of those who worked in the private sector (p = 0.038) reported that their job is stressful. In total, 21.1% of participants met Maslach's criteria for burnout. The point prevalence of burnout was as follows: (1) 13.8% of those who worked in the public sector and 25.5% of those in the private sector (2) 22.2% of males and 20% of females (3) 21.6% who were married, 18% who were single and 33.3% who were separated. Gender was found to be associated with the level of personal accomplishment (chi-squared test; p = 0.049), as 17.8% of men compared with 24.3% of women reported high personal accomplishment. The number of years of working as a physiotherapist correlated negatively (r = -0.229, p = 0.004) with the total depersonalization score. Regression analysis showed that the perception that the job is stressful (p < 0.001) and the low salary (p = 0.016) were significant predictors of high emotional exhaustion scores, while age group (p = 0.027) predicted high scores of depersonalization and the employment sector (p = 0.050) as well as the low salary predicted high personal accomplishment scores. Conclusions. Burnout levels in physiotherapists in Cyprus ranged from low to moderate

Burnout among chiropractic practitioners: real or imagined an exploratory study protocol

Burnout is a psychological syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment that has been found to exist in a significant number of healthcare and helping professionals. It imposes a significant societal burden by shortened practitioner lifespan, decreased efficiency, negative health outcomes and poorer levels of patient care. Theoretical models suggest that it appears to be the result of a complex interaction between job resources and job demands. It may be reasonable to conclude that Chiropractic professionals experience similar vocational demands and thus experience significant levels of occupational stress and subsequent burnout. However the data on burnout within the chiropractic profession is limited. It is possible that this results in significant negative outcomes on chiropractors and their patients. Therefore, the objective of this paper is to demonstrate the need to explore burnout in chiropractic practice and offer a research protocol for a potential study

Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy