The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds

We extend the effective fragment molecular orbital method (EFMO) into treating fragments connected by covalent bonds. The accuracy of EFMO is compared to FMO and conventional ab initio electronic structure methods for polypeptides including proteins. Errors in energy for RHF and MP2 are within 2 kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides similar to FMO but obtained two to five times faster. For proteins, the errors are also within a few kcal/mol of the FMO results. We developed both the RHF and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip

Comparing dogs and great apes in their ability to visually track object transpositions

Knowing that objects continue to exist after disappearing from sight and tracking invisible object displacements are two basic elements of spatial cognition. The current study compares dogs and apes in an invisible transposition task. Food was hidden under one of two cups in full view of the subject. After that both cups were displaced, systematically varying two main factors, whether cups were crossed during displacement and whether the cups were substituted by the other cup or instead cups were moved to new locations. While the apes were successful in all conditions, the dogs had a strong preference to approach the location where they last saw the reward, especially if this location remained filled. In addition, dogs seem to have especial difficulties to track the reward when both containers crossed their path during displacement. These results confirm the substantial difference that exists between great apes and dogs with regard to mental representation abilities required to track the invisible displacements of objects

On the nature and impact of self-similarity in real-time systems

In real-time systems with highly variable task execution times simplistic task models are insufficient to accurately model and to analyze the system. Variability can be tackled using distributions rather than a single value, but the proper charac- terization depends on the degree of variability. Self-similarity is one of the deep- est kinds of variability. It characterizes the fact that a workload is not only highly variable, but it is also bursty on many time-scales. This paper identifies in which situations this source of indeterminism can appear in a real-time system: the com- bination of variability in task inter-arrival times and execution times. Although self- similarity is not a claim for all systems with variable execution times, it is not unusual in some applications with real-time requirements, like video processing, networking and gaming. The paper shows how to properly model and to analyze self-similar task sets and how improper modeling can mask deadline misses. The paper derives an analyti- cal expression for the dependence of the deadline miss ratio on the degree of self- similarity and proofs its negative impact on real-time systems performance through system¿s modeling and simulation. This study about the nature and impact of self- similarity on soft real-time systems can help to reduce its effects, to choose the proper scheduling policies, and to avoid its causes at system design time.This work was developed under a grant from the European Union (FRESCOR-FP6/2005/IST/5-03402).Enrique Hernández-Orallo; Vila Carbó, JA. (2012). On the nature and impact of self-similarity in real-time systems. Real-Time Systems. 48(3):294-319. doi:10.1007/s11241-012-9146-0S294319483Abdelzaher TF, Sharma V, Lu C (2004) A utilization bound for aperiodic tasks and priority driven scheduling. IEEE Trans Comput 53(3):334–350Abeni L, Buttazzo G (1999) QoS guarantee using probabilistic deadlines. 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In: Proc of the 23rd IEEE real-time systems symposium, pp 289–300Erramilli A, Narayan O, Willinger W (1996) Experimental queueing analysis with long-range dependent packet traffic. IEEE/ACM Trans Netw 4(2):209–223Erramilli A, Roughan M, Veitch D, Willinger W (2002) Self-similar traffic and network dynamics. Proc IEEE 90(5):800–819Gardner M (1999) Probabilistic analysis and scheduling of critical soft real-time systems. Phd thesis, University of Illinois, Urbana-ChampaignGarrett MW, Willinger W (1994) Analysis, modeling and generation of self-similar vbr video traffic. In: ACM SIGCOMMHarchol-Balter M (2002) Task assignment with unknown duration. J ACM 49(2):260–288Harchol-Balter M (2007) Foreword: Special issue on new perspective in scheduling. SIGMETRICS Perform Eval Rev 34(4):2–3Harchol-Balter M, Downey AB (1997) Exploiting process lifetime distributions for dynamic load balancing. ACM Trans Comput Syst 15(3):253–285Hernandez-Orallo E, Vila-Carbo J (2007) Network performance analysis based on histogram workload models. In: Proceedings of the 15th international symposium on modeling, analysis, and simulation of computer and telecommunication systems (MASCOTS), pp 331–336Hernandez-Orallo E, Vila-Carbo J (2010) Analysis of self-similar workload on real-time systems. In: IEEE real-time and embedded technology and applications symposium (RTAS). IEEE Computer Society, Washington, pp 343–352Hernández-Orallo E, Vila-Carbó J (2010) Network queue and loss analysis using histogram-based traffic models. Comput Commun 33(2):190–201Hughes CJ, Kaul P, Adve SV, Jain R, Park C, Srinivasan J (2001) Variability in the execution of multimedia applications and implications for architecture. SIGARCH Comput Archit News 29(2):254–265Leland W, Ott TJ (1986) Load-balancing heuristics and process behavior. 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Willey, New York, Chap 1Paxson V, Floyd S (1995) Wide area traffic: the failure of Poisson modeling. IEEE/ACM Trans Netw 3(3):226–244Rolls DA, Michailidis G, Hernández-Campos F (2005) Queueing analysis of network traffic: methodology and visualization tools. Comput Netw 48(3):447–473Rose O (1995) Statistical properties of mpeg video traffic and their impact on traffic modeling in atm systems. In: Conference on local computer networksRoy N, Hamm N, Madhukar M, Schmidt DC, Dowdy L (2009) The impact of variability on soft real-time system scheduling. In: RTCSA ’09: Proceedings of the 2009 15th IEEE international conference on embedded and real-time computing systems and applications. IEEE Computer Society, Washington, pp 527–532Sha L, Abdelzaher T, Årzén KE, Cervin A, Baker T, Burns A, Buttazzo G, Caccamo M, Lehoczky J, Mok AK (2004) Real time scheduling theory: A historical perspective. 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Cellular Growth Kinetics Distinguish a Cyclophilin Inhibitor from an HSP90 Inhibitor as a Selective Inhibitor of Hepatitis C Virus

During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA) and heat-shock protein 90 (HSP90) which have each been reported to inhibit replication of hepatitis C virus (HCV). By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA), exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth

Numerosity Estimation in Visual Stimuli in the Absence of Luminance-Based Cues

Numerosity estimation is a basic preverbal ability that humans share with many animal species and that is believed to be foundational of numeracy skills. It is notoriously difficult, however, to establish whether numerosity estimation is based on numerosity itself, or on one or more non-numerical cues like-in visual stimuli-spatial extent and density. Frequently, different non-numerical cues are held constant on different trials. This strategy, however, still allows numerosity estimation to be based on a combination of non-numerical cues rather than on any particular one by itself.Here we introduce a novel method, based on second-order (contrast-based) visual motion, to create stimuli that exclude all first-order (luminance-based) cues to numerosity. We show that numerosities can be estimated almost as well in second-order motion as in first-order motion.The results show that numerosity estimation need not be based on first-order spatial filtering, first-order density perception, or any other processing of luminance-based cues to numerosity. Our method can be used as an effective tool to control non-numerical variables in studies of numerosity estimation

Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI: A Meta-Analysis of Randomized Controlled Trials

Clinical trials comparing thrombectomy devices with conventional percutaneous coronary interventions (PCI) in patients with acute ST elevation myocardial infarction (STEMI) have produced conflicting results. The objective of our study was to systematically evaluate currently available data comparing thrombectomy followed by PCI with conventional PCI alone in patients with acute STEMI

Development and Evolution of a Model Interprofessional Education Program in Parkinson’s disease: A Ten-year Experience

OBJECTIVE This paper describes development, evolution and learner reactions in a model interprofessional education program for medical, nursing, physician assistant, occupational therapy, physical therapy, music therapy, social work and speech-language pathology practitioners. Sponsored by the National Parkinson Foundation (NPF) (currently Parkinson’s Foundation), Allied Team Training for Parkinson (ATTP) is a U.S.-based multi-day interprofessional education program in best practices for integrated, interprofessional team-based Parkinson’s disease (PD) care. NPF sponsored 26 ATTP trainings from 2003 to 2013. METHODS This mixed methods evaluation uses case study document review and observation to outline ATTP curriculum development, evolution, and implementation challenges. Learner-perceived effectiveness ratings, knowledge change, pre-post ratings on the Team Skills Scale, confidence in working with people with PD and caregivers, and trainee-reported practice changes at 6-month follow-up were collected. RESULTS Qualitative results identified multiple factors in building an effective interprofessional education program, including interprofessional team practice opportunities through case-based learning, engaging care networks and continuous feedback loops for program improvement. Quantitative results showed that trainees across professions, geographic regions and work settings rated the overall program and curriculum effectiveness, amount of new knowledge and knowledge change very highly. ATTP resulted in significant post-training improvement in team skills, confidence in working with PD, and post-training self-reported practice changes. CONCLUSION Findings suggest that ATTP is an effective interprofessional education program that could be replicated or adapted to other settings and neurodegenerative or chronic illnesses. The model of combining interprofessional team training with disease-specific curriculum content appears to be an effective “next practice” in continuing professional development

Children Base Their Investment on Calculated Pay-Off

To investigate the rise of economic abilities during development we studied children aged between 3 and 10 in an exchange situation requiring them to calculate their investment based on different offers. One experimenter gave back a reward twice the amount given by the children, and a second always gave back the same quantity regardless of the amount received. To maximize pay-offs children had to invest a maximal amount with the first, and a minimal amount with the second. About one third of the 5-year-olds and most 7- and 10-year-olds were able to adjust their investment according to the partner, while all 3-year-olds failed. Such performances should be related to the rise of cognitive and social skills after 4 years