Positional candidate cloning of the RP10 form of retinitis pigmentosa

Retinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerations that affects over one million people worldwide. To date, 11 autosomal dominant, 13 autosomal recessive, and 5 X-linked forms of retinitis pigmentosa have been identified through linkage analysis, but the disease-causing genes and mutations have been found for only half of these loci. My research uses a positional candidate cloning approach to identify the gene and mutations responsible for one type of autosomal dominant retinitis pigmentosa, RP10. The premise is that identifying the genes and mutations responsible for disease will provide insight into disease mechanisms and provide treatment options. Previous research mapped the RP10 locus to a 5cM region on chromosome 7q31 between markers D7S686 and D7S530. Linkage and fine-point haplotype analysis was used to reduce and refine the RP10 disease interval to a 4cM region located between D7S2471 and a new marker located 45,000bp telomeric of D7S461. In order to identify genes located in the RP10 interval, an extensive EST map was created of this region. Five EST clusters from this map were analyzed to determine if mutations in these genes cause the RP10 form of retinitis pigmentosa. The genomic structure of a known metabotrophic glutamate receptor, GRMS8, was determined first. DNA sequencing of GRM8 in RP10 family members did not identify any disease-causing mutations. Four other EST clusters (A170, A173, A189, and A258) were characterized and determined to be part of the same gene, UBNL1 (ubinuclein-like 1). The full-length mRNA sequence and genomic structure of UBNL1 was determined and then screened in patients. No disease-causing mutations were identified in any of the RP10 family members tested. Recent data made available with the release of the public and Celera genome assemblies indicates that UBNL1 is outside of the RP10 disease region. Despite this complication, characterization of UBNL1 is still important in the understanding of normal visual processes and it is possible that mutations in UBNL1 could cause other forms of retinopathy. The EST map and list of RP10 candidates will continue to aid others in the search for the RP10 gene and mutations. ^

Cognitive Comparative Advantage and the Organization of Work: Lessons from Herbert Simon's Vision of the Future

In a marvelous but somewhat neglected paper, 'The Corporation: Will It Be Managed by Machines?' Herbert Simon articulated from the perspective of 1960 his vision of what we now call the New Economy the machine-aided system of production and management of the late twentieth century. Simon's analysis sprang from what I term the principle of cognitive comparative advantage: one has to understand the quite different cognitive structures of humans and machines (including computers) in order to explain and predict the tasks to which each will be most suited. Perhaps unlike Simon's better-known predictions about progress in artificial intelligence research, the predictions of this 1960 article hold up remarkably well and continue to offer important insights. In what follows I attempt to tell a coherent story about the evolution of machines and the division of labor between humans and machines. Although inspired by Simon's 1960 paper, I weave many other strands into the tapestry, from classical discussions of the division of labor to present-day evolutionary psychology. The basic conclusion is that, with growth in the extent of the market, we should see humans 'crowded into' tasks that call for the kinds of cognition for which humans have been equipped by biological evolution. These human cognitive abilities range from the exercise of judgment in situations of ambiguity and surprise to more mundane abilities in spatio-temporal perception and locomotion. Conversely, we should see machines 'crowded into' tasks with a well-defined structure. This conclusion is not based (merely) on a claim that machines, including computers, are specialized idiots-savants today because of the limits (whether temporary or permanent) of artificial intelligence; rather, it rests on a claim that, for what are broadly 'economic' reasons, it will continue to make economic sense to create machines that are idiots-savants.

Online Reputation Systems and Cumulative Advantage

The study of online reputation systems and their importance for promoting trust and cooperation and, therefore, the smooth functioning of online markets has received considerable attention over the last few years. In the first part of our talk we will try to give a brief overview of the existing theoretical and empirical work in this field, summarize the main findings from this research and identify open questions where results are either controversial or do not yet exist. The second part of our talk will focus on one of these issues that deserve further research, namely the relation between online reputation systems and processes of "cumulative advantage." Cumulative advantage is the mechanism where a favorable relative position of having a good reputation becomes a resource for further relative gains. The process leads to increased status inequality and a heavily skewed distribution of number of feedbacks, i.e. the ties in the reputation network. We present empirical evidence for direct and indirect reputation effects on the micro level of an auction reputation system and discuss the distributional consequences for the market level.

Skill distribution and comparative advantage: a comparison of China and India

This paper empirically examines the different comparative advantages of two emerging economic giants, China and India, in relation to the different skill distribution patterns in each country. By utilizing industry export data on China and India from 1983 to 2000, we find that a country with a greater dispersion of skills (i.e., India, especially in the earlier years) has higher exports in industries with shorter production chains, whereas a country with a more equal dispersion of skills (i.e., China, especially in the later years) is found to have higher exports in industries with longer production chains. The causal relationship is fairly robust across different specifications. This empirical evidence supports our assumption that the likely mechanism for these results is the negative impact of low-skilled workers on input quality, which accumulates and becomes larger as the length of production chains and the proportion of low-skilled workers in the economy increase.

Do electricity supply constraints matter for comparative advantage? : a neoclassical approach

This paper examines the extent to which electricity supply constraints could affect sectoral specialization. For this purpose, an empirical trade model is estimated from 1990-2008 panel data on 15 OECD countries and 12 manufacturing sectors. We find that along with Ricardian technological differences and Heckscher-Ohlin factor-endowment differences, productivity-adjusted electricity capacity drives sectoral specialization in several sectors. Among them, electrical equipment, transport equipment, machinery, chemicals, and paper products will see lower output shares as a result of decreases in productivity-adjusted electricity capacity. Furthermore, our dynamic panel estimation reveals that the effects of Ricardian technological differences dominate in the short-run, and factor endowment differences and productivity-adjusted electricity capacity tend to have a significant effect in only the long-run.

The Advantage of Arriving First: Characteristic Times in Finite Size Populations of Error-Prone Replicators

We study the evolution of a finite size population formed by mutationally isolated lineages of error-prone replicators in a two-peak fitness landscape. Computer simulations are performed to gain a stochastic description of the system dynamics. More specifically, for different population sizes, we compute the probability of each lineage being selected in terms of their mutation rates and the amplification factors of the fittest phenotypes. We interpret the results as the compromise between the characteristic time a lineage takes to reach its fittest phenotype by crossing the neutral valley and the selective value of the sequences that form the lineages. A main conclusion is drawn: for finite population sizes, the survival probability of the lineage that arrives first to the fittest phenotype rises significantly

La influencia del "Home Advantage" en el resultado de los momentos críticos en los partidos de baloncesto

El objeto de estudio del presente trabajo ha sido identificar las variables que determinan ganar o perder en los momentos críticos en los partidos de baloncesto en función de la localización del partido. Se han analizado un total de 41 momentos críticos, correspondientes a 30 partidos de la liga regular de la ACB de la temporada 2007-2008, que cumplen, según la literatura, con la noción de momento crítico y corresponden a los tiempos extras y los últimos 5 minutos de partidos donde la diferencia de puntos es menor o igual a 6. Los resultados muestran mejores valores en los equipos ganadores cuando juegan como local, en los rebotes defensivos y los tiros libres anotados; y cuando juegan como visitante en los lanzamientos de 2 puntos fallados.

Positional Accuracy in Smart-Phones and Its Effect on LBS Applications.

Location-based services (LBS) highly rely on the location of the mobile user in order to provide the service tailored to that location. This location is calculated differently depending on the technology available in the used mobile device. No matter which technology is used, the location will never be calculated 100% correctly; instead there will always be a margin of error generated during the calculation, which is referred to as positional accuracy. This research has reviewed the eight most common positioning technologies available in the major current smart-phones and assessed their positional accuracy with respect to its usage by LBS applications. Given the vast majority of these applications, this research classified them into thirteen categories, and these categories were also classified depending on their level criticality as low, medium, or high critical, and whether they function indoor or outdoor. The accuracies of different positioning technologies are compared to these two criteria. Low critical outdoor and high critical indoor applications were found technologically covered; high and medium critical outdoor ones weren?t fully resolved. Finally three potential solutions are suggested to be implemented in future smartphones to resolve this technological gap: Real-Time Kinematics Global Positioning System (RTK GPS), terrestrial transmitters, and combination of Wireless Sensors Network and Radio Frequency Identification (WSN-RFID).

Energetic considerations of ciliary beating and the advantage of metachronal coordination

The internal mechanism of cilia is among the most ancient biological motors on an evolutionary scale. It produces beat patterns that consist of two phases: during the effective stroke, the cilium moves approximately as a straight rod, and during the recovery stroke, it rolls close to the surface in a tangential motion. It is commonly agreed that these two phases are designed for efficient functioning: the effective stroke encounters strong viscous resistance and generates thrust, whereas the recovery stroke returns the cilium to starting position while avoiding viscous resistance. Metachronal coordination between cilia, which occurs when many of them beat close to each other, is believed to be an autonomous result of the hydrodynamical interactions in the system. Qualitatively, metachronism is perceived as a way for reducing the energy expenditure required for beating. This paper presents a quantitative study of the energy expenditure of beating cilia, and of the energetic significance of metachronism. We develop a method for computing the work done by model cilia that beat in a viscous fluid. We demonstrate that for a single cilium, beating in water, the mechanical work done during the effective stroke is approximately five times the amount of work done during the recovery stroke. Investigation of multicilia configurations shows that having neighboring cilia beat metachronally is energetically advantageous and perhaps even crucial for multiciliary functioning. Finally, the model is used to approximate the number of dynein arm attachments that are likely to occur during the effective and recovery strokes of a beat cycle, predicting that almost all of the available dynein arms should participate in generating the motion.

Ape-like or hominid-like? The positional behavior of Oreopithecus bambolii reconsidered

Comparative morphological and functional analyses of the skeletal remains of Oreopithecus bambolii, a hominoid from the Miocene Mediterranean island of Tuscany–Sardinia (Italy), provides evidence that bipedal activities made up a significant part of the positional behavior of this primate. The mosaic pattern of its postcranial morphology is to some degree convergent with that of Australopithecus and functionally intermediate between apes and early hominids. Some unique traits could have been selected only under insular conditions where the absence of predators and the limitation of trophic resources play a crucial role in mammalian evolution.

Phalangeal curvature and positional behavior in extinct sloth lemurs (Primates, Palaeopropithecidae)

Recent paleontological discoveries in Madagascar document the existence of a diverse clade of palaeopropithecids or “sloth lemurs”: Mesopropithecus (three species), Babakotia (one species), Palaeopropithecus (three species), and Archaeoindris (one species). This mini-radiation of now extinct (“subfossil”) lemurs is most closely related to the living indrids (Indri, Propithecus, and Avahi). Whereas the extant indrids are known for their leaping acrobatics, the palaeopropithecids (except perhaps for the poorly known giant Archaeoindris) exhibit numerous skeletal design features for antipronograde or suspensory positional behaviors (e.g., high intermembral indices and mobile joints). Here we analyze the curvature of the proximal phalanges of the hands and feet. Computed as the included angle (θ), phalangeal curvature develops in response to mechanical use and is known to be correlated in primates with hand and foot function in different habitats; terrestrial species have straighter phalanges than their arboreal counterparts, and highly suspensory forms such as the orangutan possess the most curved phalanges. Sloth lemurs as a group are characterized by very curved proximal phalanges, exceeding those seen in spider monkeys and siamangs, and approaching that of orangutans. Indrids have curvatures roughly half that of sloth lemurs, and the more terrestrial, subfossil Archaeolemur possesses the least curved phalanges of all the indroids. Taken together with many other derived aspects of their postcranial anatomy, phalangeal curvature indicates that the sloth lemurs are one of the most suspensory clades of mammals ever to evolve.

Positional enhancer-blocking activity of the chicken β-globin insulator in transiently transfected cells

It is thought that insulators demarcate transcriptionally and structurally independent chromatin domains. Insulators are detected by their ability to block enhancer–promoter interactions in a directional manner, and protect a transgene from position effects. Most studies are performed in stably transformed cells or organisms. Here we analyze the enhancer-blocking activity of the chicken β-globin insulator in transient transfection experiments in both erythroid and nonerythroid cell lines. We show that four tandem copies of a 90-bp fragment of this insulator were able to block an enhancer in these experiments. In circular plasmids, placement on either side of the enhancer reduced activity, but when the plasmid was linearized, the enhancer-blocking activity was observed only when the insulator was placed between the promoter and the enhancer. These observations are consistent with the position-dependent enhancer-blocking activity of the insulator observed in stable transformation experiments.