Modeling of negative Poisson’s ratio (auxetic) crystalline cellulose Iβ

Energy minimizations for unstretched and stretched cellulose models using an all-atom empirical force field (Molecular Mechanics) have been performed to investigate the mechanism for auxetic (negative Poisson’s ratio) response in crystalline cellulose Iβ from kraft cooked Norway spruce. An initial investigation to identify an appropriate force field led to a study of the structure and elastic constants from models employing the CVFF force field. Negative values of on-axis Poisson’s ratios nu31 and nu13 in the x1-x3 plane containing the chain direction (x3) were realized in energy minimizations employing a stress perpendicular to the hydrogen-bonded cellobiose sheets to simulate swelling in this direction due to the kraft cooking process. Energy minimizations of structural evolution due to stretching along the x3 chain direction of the ‘swollen’ (kraft cooked) model identified chain rotation about the chain axis combined with inextensible secondary bonds as the most likely mechanism for auxetic response

Structure of Protein Interaction Networks and Their Implications on Drug Design

Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects

Electronic health records in outpatient clinics: Perspectives of third year medical students

Abstract Background United States academic medical centers are increasingly incorporating electronic health records (EHR) into teaching settings. We report third year medical students' attitudes towards clinical learning using the electronic health record in ambulatory primary care clinics. Methods In academic year 2005–06, 60 third year students were invited to complete a questionnaire after finishing the required Ambulatory Medicine/Family Medicine clerkship. The authors elicited themes for the questionnaire by asking a focus group of third year students how using the EHR had impacted their learning. Five themes emerged: organization of information, access to online resources, prompts from the EHR, personal performance (charting and presenting), and communication with patients and preceptors. The authors added a sixth theme: impact on student and patient follow-up. The authors created a 21-item questionnaire, based on these themes that used a 5-point Likert scale from "Strongly Agree" to "Strongly Disagree". The authors emailed an electronic survey link to each consenting student immediately following their clerkship experience in Ambulatory Medicine/Family Medicine. Results 33 of 53 consenting students (62%) returned completed questionnaires. Most students liked the EHR's ability to organize information, with 70% of students responding that essential information was easier to find electronically. Only 36% and 33% of students reported accessing online patient information or clinical guidelines more often when using the EHR than when using paper charts. Most students (72%) reported asking more history questions due to EHR prompts, and 39% ordered more clinical preventive services. Most students (69%) reported that the EHR improved their documentation. 39% of students responded that they received more feedback on their EHR notes compared to paper chart notes. Only 64% of students were satisfied with the doctor-patient communication with the EHR, and 48% stated they spent less time looking at the patient. Conclusion Third year medical students reported generally positive attitudes towards using the EHR in the ambulatory setting. They reported receiving more feedback on their electronic charts than on paper charts. However, students reported significant concerns about the potential impact of the EHR on their ability to conduct the doctor-patient encounter.Peer Reviewe

The appended curve technique for deconvolutional analysis —method and validation

Deconvolutional analysis (DCA) is useful in correction of organ time activity curves (response function) for variations in blood activity (input function). Despite enthusiastic reports of applications of DCA in renal and cardiac scintigraphy, routine use has awaited an easily implemented algorithm which is insensitive to statistical noise. The matrix method suffers from the propagation of errors in early data points through the entire curve. Curve fitting or constraint methods require prior knowledge of the expected form of the results. DCA by Fourier transforms (FT) is less influenced by single data points but often suffers from high frequency artifacts which result from the abrupt termination of data acquisition at a nonzero value.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46829/1/259_2004_Article_BF00254393.pd

Equivalence and noninferiority trials – are they viable alternatives for registration of new drugs? (III)

The scientific community's reliance on active-controlled trials is steadily increasing, as widespread agreement emerges concerning the role of these trials as viable alternatives to placebo trials. These trials present substantial challenges with regard to design and interpretation as their complexity increases, and the potential need for larger sample sizes impacts the cost and time variables of the drug development process. The potential efficacy and safety benefits derived from these trials may never be demonstrated by other methods. Active-controlled trials can develop valuable data to inform both prescribers and patients about the dose- and time-dependent actions of any new drug and can contribute to the management and communication of risks associated with the relevant therapeutic products

Voice-selective prediction alterations in nonclinical voice hearers

Auditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but also occur in 6-13% of the general population. Voice perception is thought to engage an internal forward model that generates predictions, preparing the auditory cortex for upcoming sensory feedback. Impaired processing of sensory feedback in vocalization seems to underlie the experience of AVH in psychosis, but whether this is the case in nonclinical voice hearers remains unclear. The current study used electroencephalography (EEG) to investigate whether and how hallucination predisposition (HP) modulates the internal forward model in response to self-initiated tones and self-voices. Participants varying in HP (based on the Launay-Slade Hallucination Scale) listened to self-generated and externally generated tones or self-voices. HP did not affect responses to self vs. externally generated tones. However, HP altered the processing of the self-generated voice: increased HP was associated with increased pre-stimulus alpha power and increased N1 response to the self-generated voice. HP did not affect the P2 response to voices. These findings confirm that both prediction and comparison of predicted and perceived feedback to a self-generated voice are altered in individuals with AVH predisposition. Specific alterations in the processing of self-generated vocalizations may establish a core feature of the psychosis continuum.The Authors gratefully acknowledge all the participants who collaborated in the study, and particularly Dr. Franziska Knolle for feedback on stimulus generation, Carla Barros for help with scripts for EEG time-frequency analysis, and Dr. Celia Moreira for her advice on mixed linear models. This work was supported by the Portuguese Science National Foundation (FCT; grant numbers PTDC/PSI-PCL/116626/2010, IF/00334/2012, PTDC/MHCPCN/0101/2014) awarded to APP

Five Nuclear Loci Resolve the Polyploid History of Switchgrass (Panicum virgatum L.) and Relatives

Polyploidy poses challenges for phylogenetic reconstruction because of the need to identify and distinguish between homoeologous loci. This can be addressed by use of low copy nuclear markers. Panicum s.s. is a genus of about 100 species in the grass tribe Paniceae, subfamily Panicoideae, and is divided into five sections. Many of the species are known to be polyploids. The most well-known of the Panicum polyploids are switchgrass (Panicum virgatum) and common or Proso millet (P. miliaceum). Switchgrass is in section Virgata, along with P. tricholaenoides, P. amarum, and P. amarulum, whereas P. miliaceum is in sect. Panicum. We have generated sequence data from five low copy nuclear loci and two chloroplast loci and have clarified the origin of P. virgatum. We find that all members of sects. Virgata and Urvilleana are the result of diversification after a single allopolyploidy event. The closest diploid relatives of switchgrass are in sect. Rudgeana, native to Central and South America. Within sections Virgata and Urvilleana, P. tricholaenoides is sister to the remaining species. Panicum racemosum and P. urvilleanum form a clade, which may be sister to P. chloroleucum. Panicum amarum, P. amarulum, and the lowland and upland ecotypes of P. virgatum together form a clade, within which relationships are complex. Hexaploid and octoploid plants are likely allopolyploids, with P. amarum and P. amarulum sharing genomes with P. virgatum. Octoploid P. virgatum plants are formed via hybridization between disparate tetraploids. We show that polyploidy precedes diversification in a complex set of polyploids; our data thus suggest that polyploidy could provide the raw material for diversification. In addition, we show two rounds of allopolyploidization in the ancestry of switchgrass, and identify additional species that may be part of its broader gene pool. This may be relevant for development of the crop for biofuels