Towards cheap, accurate polymorphism detection

Polymorphism, along with inheritance, is one of the most important features in object-oriented languages, but it is also one of the biggest obstacles to source code comprehension. Depending on the run-time type of the receiver of a message, any one of a number of possible methods may be invoked. Several algorithms for creating accurate call-graphs using static analysis already exist, however, they consume significant time and memory resources. We propose an approach that will combine static and dynamic analysis and yield the best possible precision with a minimal trade-off between used resources and accuracy.

Development of synesthesia across the adult lifespan

In synesthesia, stimuli such as sounds, words or letters trigger experiences of colors, shapes or tastes. The consistency of these experiences is a hallmark of this condition. In a previous study we investigated for the first time whether there are age-related changes in the consistency of synesthetic experiences. Using a cross-sectional approach, we tested a sample of more than 400 grapheme-color synesthetes who have color experiences when they see letters and/or digits with a well-established test of consistency. Our results showed a decline in the number of consistent grapheme-color associations across the adult lifespan. We also assessed age-related changes in the breadth of the color spectrum. The results showed that the appearance of primary colors (i.e., red, blue, and green) was mainly age-invariant. However, there was a decline in the occurrence of lurid colors while brown and achromatic tones occurred more often as concurrents in older age. These shifts in the color spectrum suggest that synesthesia does not simply fade, but rather undergoes more comprehensive changes. These changes may be the result of a combination of both age-related perceptual and memory processing shifts. I will present the results of a second wave of data acquisition after a one-year interval to investigate the longitudinal age-related trajectory of the consistency of synesthetic experiences.

Cognitive improvement in patients with carotid stenosis is independent of treatment type

Treatment of carotid artery stenosis decreases the long-term risk of stroke and may enhance cerebral blood flow. It is therefore expected to have the potential to prevent cognitive decline or even improve cognition over the long-term. However, intervention itself can cause peri-interventional cerebral infarcts, possibly resulting in a decline of cognitive performance, at least for a short time. We investigated the long-term effects of three treatment methods on cognition and the emotional state one year after intervention. In this prospective observational cohort study, 58 patients with extracranial carotid artery stenosis (≥70%) underwent magnetic resonance imaging and assessment of cognition, mood and motor speed before carotid endarterectomy (n = 20), carotid stenting (n = 10) or best medical treatment (n = 28) (i.e., time-point 1 [TP1]), and at one-year follow-up (TP2). Gain scores, reflecting cognitive change after treatment, were built according to performance as (TP2 -TP1)/TP1. Independent of the treatment type, significant improvement in frontal lobe functions, visual memory and motor speed was found. Performance level, motor speed and mood at TP1 were negatively correlated with gain scores, with greater improvement in patients with low performance before treatment. Active therapy, whether conservative or interventional, produces significant improvement of frontal lobe functions and memory in patients with carotid artery disease, independent of treatment type. This effect was particularly pronounced in patients with low cognitive performance prior to treatment.

Correcting misconceptions about synaesthesia

In the annals of cognitive neuroscience there are examples of fantastic memory abilities (e.g., Luria, 1968) that befuddle the vast majority of us with normal mnemonic skills. Although such feats have yet to be demonstrated in other species, extraordinary memory may not be unique to humans. One possible example comes from a study by Inoue and Matsuzawa (2007), which showed that following extensive training, a chimpanzee, Ayumu, displayed superior working memory than human volunteers. Recently, Humphrey (2012) hypothesized that Ayumu outperformed the human participants because he had synaesthesia, a condition in which a stimulus (an inducer) will involuntarily elicit an atypical ancillary experience (a concurrent) (e.g., graphemes eliciting color photisms) (Ward, 2013). Specifically, Humphrey posits that Ayumu spontaneously developed grapheme-colour synaesthesia through “cross-cortical leakage” (p. 354) between the parietal cortex, which may support the storage of overlearned sequences, and adjacent colour-coding regions, during working memory training. Humphrey speculates that the synaesthetic associations elicited colour after-images during training with numerals, and, in turn, facilitated superior performance. Here we challenge this hypothesis and argue that it makes a number of assumptions that are not supported by current research.

Cerebellar Pathology Does Not Impair Performance on Identification or Categorization Tasks

In comparison to the basal ganglia, prefrontal cortex, and medial temporal lobes, the cerebellum has been absent from recent research on the neural substrates of categorization and identification, two prominent tasks in the learning and memory literature. To investigate the contribution of the cerebellum to these tasks, we tested patients with cerebellar pathology (seven with bilateral degeneration, six with unilateral lesions, and two with midline damage) on rule-based and information-integration categorization tasks and an identification task. In rule-based tasks, it is assumed that participants learn the categories through an explicit reasoning process. In information-integration tasks, optimal performance requires the integration of information from multiple stimulus dimensions, and participants are typically unaware of the decision strategy. The identification task, in contrast, required participants to learn arbitrary, color-word associations. The cerebellar patients performed similar to matched controls on all three tasks and performance did not vary with the extent of cerebellar pathology. Although the interpretation of these null results requires caution, these data contribute to the current debate on cerebellar contributions to cognition by providing boundary conditions on understanding the neural substrates of categorization and identification, and help define the functional domain of the cerebellum in learning and memory.

Behavioral Implications of Knockout for the Dyslexia-Risk Gene Dcdc2 in Mice

Several genetic linkage and epidemiological studies have provided strong evidence that DCDC2 is a candidate gene for developmental dyslexia, a disorder that impairs a person’s reading ability despite adequate intelligence, education, and socio-economic status. Studies investigating embryonic intra-ventricular RNA interference (RNAi) of Dcdc2, a rat homolog of the DCDC2 gene in humans, indicate disruptions in neuronal migration in the rat cortex during development. Interestingly, these anatomical anomalies are consistent with post mortem histological analysis of human dyslexic patients. Other rodent models of cortical developmental disruption have shown impairment in rapid auditory processing and learning maze tasks in affected subjects. The current study investigates the rapid auditory processing abilities of mice heterozygous for Dcdc2 (one functioning Dcdc2 allele) and mice with a homozygous knockout of Dcdc2 (no functioning Dcdc2 allele). It is important to note that this genetic model for behavioral assessment is still in the pilot stage. However, preliminary results suggest that mice with a genetic mutation of Dcdc2 have impaired rapid auditory processing, as well as non-spatial maze learning and memory ability, as compared to wildtypes. By genetically knocking out Dcdc2 in mice, behavioral features associated with Dcdc2 can be characterized, along with other neurological abnormalities that may arise due to the loss of the functioning gene.

Diversity in T cell costimulation by alpha4beta1 integrin

T cell activation requires antigen-specific T cell receptor signals that spatially and temporally coincide with a second costimulatory signal. CD28 and α4β1 integrin both function as T cell costimulators, but their individual mechanisms remain elusive. By directly comparing CD3-dependent functions and signaling pathways employed by these two costimulatory receptors, aspects of their individual signaling mechanisms are explored. We determined that CD28 and α4β1 integrins both use Src-family kinase Lck and MAPK Erk, but to different extents and functional ends. After identifying functional differences between CD28 and integrin costimulatory pathways, the focus of the study turned to integrin signaling in naïve and memory T cell subsets. CD45RO T cells are fully co-activated by natural β1 integrin ligands fibronectin (FN) and VCAM-1, β1 monoclonal antibody 33B6, as well as α4β1 monoclonal antibody 19H8 which binds a combinatorial epitope of the α4β1 heterodimer. While CD28 fully costimulates CD45RA T cells, the degree of activation from integrin ligands varies. FN costimulates CD3-dependent proliferation, IL-2 secretion, and early activation markers CD25 and CD69. However, β1 antibody 33B6, which binds to the same T cell integrins (α4β1 and α5β1) as natural ligand FN, failed to costimulate proliferation or IL-2 in the CD45RA subset, but retained the ability to regulate CD25 and CD69. Unique aspects of 19H8 signaling involve early Erk activation and IL-2 independent proliferation. Signaling defects through 33B6 ligation correlates with poor adhesion under fluid flow conditions, suggesting a cytoskeletal basis for signaling. All together, these data provide evidence for a mechanism of α4β1 integrin signaling and describe functional differences between naïve and memory T cells. ^

The impact of functional impairment on the survival of patients with Alzheimer's disease

Alzheimer's disease (AD), the most common form of dementia, is the fifth leading cause of death among U.S. adults aged 65 or older. Most AD patients have shorter life expectancy compared with older people without dementia. This disease has become an enormous challenge in the aging society and is also a global problem. Not only do families of patients with Alzheimer's disease need to pay attention to this problem, but also the healthcare system and society as a whole have to confront. In dementia, functional impairment is associated with basic activities of daily living (ADL) and instrumental activities of daily living (IADL). For patients with Alzheimer's disease, problems typically appear in performing IADL and progress to the inability of managing less complex ADL functions of personal care. Thus, assessment of ADLs can be used for early accurate diagnosis of Alzheimer's disease. It should be useful for patients, caregivers, clinicians, and policy planners to estimate the survival of patients with Alzheimer's disease. However, it is unclear that when making predictions of patient outcome according to their histories, time-dependent covariates will provide us with important information on how changes in a patient's status can effect the survival. In this study, we examined the effect of impaired basic ADL as measured by the Physical Self-Maintenance Scale (PSMS) and utilized a multistate survival analysis approach to estimate the probability of death in the first few years of initial visit for AD patients taking into consideration the possibility of impaired basic ADL. The dataset used in this study was obtained from the Baylor Alzheimer's Disease and Memory Disorders Center (ADMDC). No impaired basic ADL and older age at onset of impaired basic ADL were associated with longer survival. These findings suggest that the occurrence of impaired basic ADL and age at impaired basic ADL could be predictors of survival among patients with Alzheimer's disease. ^

The role of plasmacytoid dendritic cells in the regulation of adaptive immunity

Plasmacytoid dendritic cells (pDCs) selectively express TLR7 which allows them to respond to RNA viruses and TLR9 which allows them to respond to DNA viruses and CpG oligonucleotides. Upon exposure to virus pDCs produce vast amounts of type I interferon (IFN) directly inhibiting viral replication and contributing to the activation of other immune cells. The ability of pDCs to promote B and T cell differentiation through type I IFN has been well documented although the role of additional factors including tumor necrosis factor (TNF) family members has not been thoroughly addressed. Here the expression of selected TNF family members in pDCs was examined and the role of TNF receptor-ligand interactions in the regulation of B and T lymphocyte growth and differentiation by pDCs was investigated. Upon stimulation with CpG-B, pDCs exhibit strong and stable expression of CD70, a TNF family ligand that binds to its receptor CD27 on memory B cells and promotes plasma cell differentiation and Ig secretion. Using an in vitro pDC/B cell co-culture system, it was determined that CpG-B-stimulated pDCs induce the proliferation of CD40L-activated human peripheral B cells and Ig secretion. This occurs independently of IFN and residual CpG, and requires physical contact between pDCs and B cells. CpG-stimulated pDCs induce the proliferation of both naive and memory B cells although Ig secretion is restricted to the memory subset. Blocking the interaction of CD70 with CD27 using an antagonist anti-CD70 antibody reduces the induction of B cell proliferation and IgG secretion by CpG-B-stimulated pDCs. Published studies have also indicated an important role for CD70 in promoting the expansion of CD4+ and CD8+ T cells and the development of effector function. CpG-B-stimulated pDCs induce naïve CD4+ T cell proliferation and production of multiple cytokines including IFN-γ, TNF-α, IL-10, IL-4, IL-5 and IL-13. Blocking the function of CD70 with an antagonist anti-CD70 antibody significantly reduced the induction of naïve CD4+ T cell proliferation by CpG-B-stimulated pDCs and the production of IL-4 and IL-13. Collectively these data indicate an important role for CD70 in the regulation of B and T lymphocyte growth and differentiation by pDCs. ^

Polybrominated diphenyl ether (PBDE) exposure in North Americans: Cause for concern?

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants (BFRs) that have been widely produced and used as flame retardants since the 1970’s in many consumer products such as carpet and drape linings, plastics used in electronics, computer and television casings and polyurethane foam used in chairs, sofas and mattresses. PBDEs are persistent organic pollutants (POPs), which, by definition, are toxic in nature, persistent in the environment and accumulative in living organisms. Animal studies have found PBDEs to cause health defects such as fetal malformations, delayed onset of puberty, decreased sperm count, behavioral changes, permanent learning and memory impairment, endocrine disruption, as well as cancer at high doses. Recent research involving humans reported that elevated breast milk PBDEs levels in their mothers are associated with cryptorchidism (absence of one or both testes from the scrotum) in newborn boys and adverse birth outcomes as well as elevated serum PBDE levels in mothers are associated with low sperm count in young men. There are three commonly manufactured PBDE commercial mixtures: Penta-, Octa-, and Deca-BDEs. Two of them (Octa- and Penta-BDEs) have been banned by the European Union and are being voluntarily phased out in the United States. However, Deca continues to be manufactured, used, and imported in the United States. This MPH thesis consists of a literature review of peer reviewed scientific articles concerned with PBDEs in the environment and in humans, as well as a discussion concerning different routes of exposure to PBDEs and their blood, milk and tissue levels as surrogates for body burdens in North Americans and in people from other countries. Results of this literature review shows PBDE levels in human blood, milk and tissues are higher in North Americans than people from other countries worldwide. To date, the highest level of PBDEs was found in a toddler’s blood in a California study. Despite the fact that PBDEs are associated with adverse health effects, and highest levels of PBDEs in North Americans, Deca-BDE is still manufactured, used and imported in the United States. There is an urgent need of new federal regulatory policy to ban completely the production, importation and use of all commercial mixtures of PBDEs.^

Ensayo, viaje y memoria : lectura de El destino de un continente (1923) de Manuel Ugarte

Dentro del corpus ensayístico de Manuel Ugarte figura una obra titulada El destino de un continente (1923) que da cuenta de su gira por el continente americano. El propósito de este largo viaje que emprende Ugarte es de carácter propagandístico, pues sostiene públicamente —a través de conferencias, mítines— la tesis de la unidad continental como estrategia defensiva contra la política intervencionista norteamericana. Pareciera, inicialmente, que el texto en cuestión merecería un abordaje desde los estudios de la literatura de viaje, lo que es en sí mismo correcto aunque, a nuestro entender, insuficiente. De manera que tenemos un problema de orden genérico que bien vale la pena plantear a fin de ajustar nuestra lectura. Es cierto que se trata de un viaje, pero no de un viaje cualquiera, en términos de un sujeto que se traslada de un sitio a otro con propósitos meramente turísticos, sino que la motivación central del desplazamiento ugarteano se sitúa en una acción catequística, si se quiere, de prédica que pretende mover a la acción.

El paisaje como patrimonio : paisaje costero del canal Zanjón Cacique Guaymallén : investigación, sistematización y propuesta

El objetivo del trabajo ha sido la revalorización del Canal Zanjón Cacique Guaymallén como un patrimonio cultural ambiental de los mendocinos. La metodología aplicada incluye el análisis de la trayectoria histórica del asentamiento del Gran Mendoza, el zanjón como parte de la cuenca del río Mendoza, como parte del sistema de drenaje, como parte del sistema de riego. Luego, el reconocimiento de los paisajes particulares del zanjón y una posterior catalogación y ordenación, con el fin de ser material útil al planificador territorial primero y al diseñador urbano después. A modo de conclusión el autor menciona la necesidad implícita de proteger, enriquecer e integrar a la vida y memoria urbanos el cauce, las márgenes, el entorno y el oasis al que da vida el zanjón; junto con la urgencia de proyectar a futuro nuevamente los cursos de agua como potenciales ordenadores del territorio y su rol central en la planificación urbana.

Los primeros sobrevivientes de la Shoa en Argentina : su imagen y memoria en la sociedad general y judía: 1945-50 (Primera Parte)

En la primera parte de esta indagación histórica se explora la imagen de los sobrevivientes en la sociedad general, con el trasfondo de la política inmigratoria argentina del peronismo entre 1946-50 que discriminaba a los refugiados judíos; después se indaga el lugar de la ayuda a esos sobrevivientes dentro de las prioridades de la comunidad judía organizada. Finalmente, se aborda un aspecto aún no investigado: el esfuerzo solitario de sus familiares residentes en Argentina para procurar, de organizaciones locales comunitarias e internacionales judías, el ingreso y socorro a los sobrevivientes que fueron localizados en los campos de personas desplazadas (DPs) y en otros lugares de Europa. Además se explora el impacto y memoria de la Shoa en los esfuerzos de reconstitución comunitaria a nivel institucional y educativa de la Kheila de Buenos Aires, realizados durante los primeros años de posguerra cuando la ayuda a los sobrevivientes que empezaban a arribar a Argentina quedó librada a la solitaria solidaridad de sus familiares locales y de asociaciones de coterráneos. Dada su extensión, aquí se publica la primera parte de este trabajo, el cual será completado en el número siguiente

El lado B de la historia, un caso de violencia política en el corregimiento de Arauca, Caldas, Colombia, el 29 y 30 de octubre de 1949

Investigar 'el lado B' de la Historia proporciona otras respuestas y perspectivas para comprender un hecho traumático ocurrido el 29 de octubre de 1949 en Arauca, Caldas; cuando 49 personas perdieron su vida en el contexto histórico de lo que la Violentología denomina en Colombia 'La violencia'. Las indagaciones se circunscriben en el orden de ¿Qué pasó?, ¿Cómo pasó? y ¿Qué se ha narrado? Ya que las respuestas difieren, esencialmente, dependiendo de si las versiones provienen del diario manizalita 'La Patria' y la historia oficial, donde la autoría de los asesinatos fue atribuida a los liberales gaitanistas; o de fuentes tales como: el diario 'El Tiempo', los archivos judiciales, los testimonios orales de las víctimas sobrevivientes, los álbumes fotográficos y la asistencia de los estudios de memoria, donde se evidencia que la masacre fue ejecutada por la Policía, las fuerzas paramilitares de la época, conocidos como "los pájaros", y civiles conservadores que a su vez fueron la pieza procesal para iniciar la investigación judicial tendiente a "esclarecer" los hechos

La identidad y la memoria : Una experiencia de campo en el norte cordobés

En los últimos 20 años se han producidos en el norte de la provincia de de Córdoba, cambios en la estructura agraria -uso, tenencia y distribución de la tierra-. Los cambios en el uso del suelo como desmonte para la producción ganadera bovina, produjeron variaciones en la distribución de la tierra, provocando la concentración de este recurso. Esto ha acentuado la ya existente marcada polarización de pequeñas y grandes explotaciones. En cuanto a la tenencia, se agrava la situación de algunas familias campesinas sin título de propiedad, generándose conflictos por la permanencia de dichas familias, que hace más de 20 años no constituía una limitante para éstos sistemas productivos. En el contexto descripto, se llevó adelante el trabajo en terreno que tuvo por objetivo apoyar el proceso de organización por medio de la construcción de la historia de la comunidad y su reconstrucción a partir de los integrantes de la misma. Es así que del análisis de la memoria surge la asociación de ésta con la identidad de los sujetos que recuerdan: los campesinos. En el presente trabajo se busca explicar la relación entre la memoria colectiva y la identidad de la comunidad campesina de "La Costa", situada en el noroeste de la provincia de Córdoba, República Argentina.