Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

NMR of liquid 3He in clay pores at 1.5 K

In the present work a new method for studying porous media by nuclear magnetic resonance of liquid 3He has been proposed. This method has been demonstrated in an example of a clay mineral sample. For the first time the integral porosity of clay sample has been measured. For investigated samples the value of integral porosity is in the range of 10-30%. Inverse Laplace transform of 3He longitudinal magnetization recovery curve has been carried out, thus distribution of relaxation times T1 has been obtained.Comment: 9 pages, 5 figure

Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

The braincase and jaws of a Devonian 'acanthodian' and modern gnathostome origins.

Modern gnathostomes (jawed vertebrates) emerged in the early Palaeozoic era, but this event remains unclear owing to a scant early fossil record. The exclusively Palaeozoic acanthodians are possibly the earliest gnathostome group and exhibit a mosaic of shark- and bony fish-like characters that has long given them prominence in discussions of early gnathostome evolution. Their relationships with modern gnathostomes have remained mysterious, partly because their un-mineralized endoskeletons rarely fossilized. Here I present the first-known braincase of an Early Devonian (approximately 418-412 Myr bp) acanthodian, Ptomacanthus anglicus, and re-evaluate the interrelationships of basal gnathostomes. Acanthodian braincases have previously been represented by a single genus, Acanthodes, which occurs more than 100 million years later in the fossil record. The braincase of Ptomacanthus differs radically from the osteichthyan-like braincase of Acanthodes in exhibiting several plesiomorphic features shared with placoderms and some early chondrichthyans. Most striking is its extremely short sphenoid region and its jaw suspension, which displays features intermediate between some Palaeozoic chondrichthyans and osteichthyans. Phylogenetic analysis resolves Ptomacanthus as either the most basal chondrichthyan or as the sister group of all living gnathostomes. These new data alter earlier conceptions of basal gnathostome phylogeny and thus help to provide a more detailed picture of the acquisition of early gnathostome characters

What Values in Design? The Challenge of Incorporating Moral Values into Design

Recently, there is increased attention to the integration of moral values into the conception, design, and development of emerging IT. The most reviewed approach for this purpose in ethics and technology so far is Value-Sensitive Design (VSD). This article considers VSD as the prime candidate for implementing normative considerations into design. Its methodology is considered from a conceptual, analytical, normative perspective. The focus here is on the suitability of VSD for integrating moral values into the design of technologies in a way that joins in with an analytical perspective on ethics of technology. Despite its promising character, it turns out that VSD falls short in several respects: (1) VSD does not have a clear methodology for identifying stakeholders, (2) the integration of empirical methods with conceptual research within the methodology of VSD is obscure, (3) VSD runs the risk of committing the naturalistic fallacy when using empirical knowledge for implementing values in design, (4) the concept of values, as well as their realization, is left undetermined and (5) VSD lacks a complimentary or explicit ethical theory for dealing with value trade-offs. For the normative evaluation of a technology, I claim that an explicit and justified ethical starting point or principle is required. Moreover, explicit attention should be given to the value aims and assumptions of a particular design. The criteria of adequacy for such an approach or methodology follow from the evaluation of VSD as the prime candidate for implementing moral values in design

Fatal Prion Disease in a Mouse Model of Genetic E200K Creutzfeldt-Jakob Disease

Genetic prion diseases are late onset fatal neurodegenerative disorders linked to pathogenic mutations in the prion protein-encoding gene, PRNP. The most prevalent of these is the substitution of Glutamate for Lysine at codon 200 (E200K), causing genetic Creutzfeldt-Jakob disease (gCJD) in several clusters, including Jews of Libyan origin. Investigating the pathogenesis of genetic CJD, as well as developing prophylactic treatments for young asymptomatic carriers of this and other PrP mutations, may well depend upon the availability of appropriate animal models in which long term treatments can be evaluated for efficacy and toxicity. Here we present the first effective mouse model for E200KCJD, which expresses chimeric mouse/human (TgMHu2M) E199KPrP on both a null and a wt PrP background, as is the case for heterozygous patients and carriers. Mice from both lines suffered from distinct neurological symptoms as early as 5–6 month of age and deteriorated to death several months thereafter. Histopathological examination of the brain and spinal cord revealed early gliosis and age-related intraneuronal deposition of disease-associated PrP similarly to human E200K gCJD. Concomitantly we detected aggregated, proteinase K resistant, truncated and oxidized PrP forms on immunoblots. Inoculation of brain extracts from TgMHu2ME199K mice readily induced, the first time for any mutant prion transgenic model, a distinct fatal prion disease in wt mice. We believe that these mice may serve as an ideal platform for the investigation of the pathogenesis of genetic prion disease and thus for the monitoring of anti-prion treatments

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Gene Order Phylogeny of the Genus Prochlorococcus

Using gene order as a phylogenetic character has the potential to resolve previously unresolved species relationships. This character was used to resolve the evolutionary history within the genus Prochlorococcus, a group of marine cyanobacteria.Orthologous gene sets and their genomic positions were identified from 12 species of Prochlorococcus and 1 outgroup species of Synechococcus. From this data, inversion and breakpoint distance-based phylogenetic trees were computed by GRAPPA and FastME. Statistical support of the resulting topology was obtained by application of a 50% jackknife resampling technique. The result was consistent and congruent with nucleotide sequence-based and gene-content based trees. Also, a previously unresolved clade was resolved, that of MIT9211 and SS120.This is the first study to use gene order data to resolve a bacterial phylogeny at the genus level. It suggests that the technique is useful in resolving the Tree of Life

Patients' experiences with quality of hospital care: the Consumer Quality Index Cataract Questionnaire

Background. Patients' feedback is of great importance in health care policy decisions. The Consumer Quality Index Cataract Questionnaire (CQI Cataract) was used to measure patients' experiences with quality of care after a cataract operation. This study aims to evaluate the reliability and the dimensional structure of this questionnaire and assesses its ability to measure differences between hospitals in patients' experiences with quality of care. Methods. Survey data of 4,635 respondents were available. An exploratory factor analysis was performed to evaluate the construct validity of the questionnaire and item-correlations and inter-factor correlations were calculated. Secondly, Cronbach's alpha coefficients were calculated to assess the internal consistency of the scales. Thirdly, to evaluate the ability of the questionnaire to discriminate between hospitals, multilevel analyses were performed with patients hierarchically nested within hospitals. Results. Exploratory factor analysis resulted in 14 quality of care items subdivided over three factors (i.e. communication with ophthalmologist, communication with nurses, and communication about medication). Cronbach's alpha coefficients of 0.89, 0.76 and 0.79 indicated good internal consistency. Multilevel analyses showed that the questionnaire was able to measure differences in patients' experiences with hospital care regarding communication with ophthalmologist and communication about medication. In addition, there was variation between hospitals regarding ophthalmologist ratings, hospital ratings and one dichotomous information item. Conclusion. These findings suggest that the CQI Cataract is a reliable and valid instrument. This instrument can be used to measure patients' experiences with three domains of hospital care after a cataract operation and is able to assess differences in evaluated care between hospitals