LAP6/WVU system outline

Operating manual for additional memory for PDP 12 and LINC 8 computer

English Language Proficiency and Geographical Proximity to a Safety Net Clinic as a Predictor of Health Care Access

Studies suggest that proximity to a safety net clinic (SNC) promotes access to care among the uninsured. Distance-based barriers to care may be greater for people with limited English proficiency (LEP), compared to those who are English proficient (EP), but this has not been explored. We assessed the relationship between distance to the nearest SNC and access in non-rural uninsured adults in California, and examined whether this relationship differs by language proficiency. Using the 2005 California Health Interview Survey and a list we compiled of California’s SNCs, we calculated distance between uninsured interviewee residence and the exact address of the nearest SNC. Using multivariate regression to adjust for other relevant characteristics, we examined associations between this distance and interviewee’s probability of having a usual source of health care (USOC) and having visited a physician in the prior 12 months. To examine differences by language proficiency, we included interactions between distance and language proficiency. Uninsured LEP adults living within 2 miles of a SNC were 9.3% less likely than their EP counterparts to have a USOC (P = 0.046). Further, distance to the nearest SNC was inversely associated with the probability of having a USOC among LEP, but not among EP; consequently, the difference between LEP and EP in the probability of having a USOC widened with increasing distance to the nearest SNC. There was no difference between LEP and EP adults living within 2 miles of a SNC in likelihood of having a physician visit; however, as with USOC, distance to the nearest SNC was inversely associated with the probability of having a physician visit among LEP but not EP. The effect sizes diminished, but remained significant, when we included county fixed effects in the models. Having LEP is a barrier to health care access, which compounds when combined with increased distance to the nearest SNC, among uninsured adults. Future studies should explore potential mechanisms so that appropriate interventions can be implemented

Distinct Haptic Cues Do Not Reduce Interference when Learning to Reach in Multiple Force Fields

Background: Previous studies of learning to adapt reaching movements in the presence of novel forces show that learning multiple force fields is prone to interference. Recently it has been suggested that force field learning may reflect learning to manipulate a novel object. Within this theoretical framework, interference in force field learning may be the result of static tactile or haptic cues associated with grasp, which fail to indicate changing dynamic conditions. The idea that different haptic cues (e.g. those associated with different grasped objects) signal motor requirements and promote the learning and retention of multiple motor skills has previously been unexplored in the context of force field learning. Methodology/Principle Findings: The present study tested the possibility that interference can be reduced when two different force fields are associated with differently shaped objects grasped in the hand. Human subjects were instructed to guide a cursor to targets while grasping a robotic manipulandum, which applied two opposing velocity-dependent curl fields to the hand. For one group of subjects the manipulandum was fitted with two different handles, one for each force field. No attenuation in interference was observed in these subjects relative to controls who used the same handle for both force fields. Conclusions/Significance: These results suggest that in the context of the present learning paradigm, haptic cues on their own are not sufficient to reduce interference and promote learning multiple force fields

Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity

Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23-87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss

Origins of the Tumor Microenvironment: Quantitative Assessment of Adipose-Derived and Bone Marrow–Derived Stroma

To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA+ myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner

Detection and Functional Characterization of a 215 Amino Acid N-Terminal Extension in the Xanthomonas Type III Effector XopD

During evolution, pathogens have developed a variety of strategies to suppress plant-triggered immunity and promote successful infection. In Gram-negative phytopathogenic bacteria, the so-called type III protein secretion system works as a molecular syringe to inject type III effectors (T3Es) into plant cells. The XopD T3E from the strain 85-10 of Xanthomonas campestris pathovar vesicatoria (Xcv) delays the onset of symptom development and alters basal defence responses to promote pathogen growth in infected tomato leaves. XopD was previously described as a modular protein that contains (i) an N-terminal DNA-binding domain (DBD), (ii) two tandemly repeated EAR (ERF-associated amphiphillic repression) motifs involved in transcriptional repression, and (iii) a C-terminal cysteine protease domain, involved in release of SUMO (small ubiquitin-like modifier) from SUMO-modified proteins. Here, we show that the XopD protein that is produced and secreted by Xcv presents an additional N-terminal extension of 215 amino acids. Closer analysis of this newly identified N-terminal domain shows a low complexity region rich in lysine, alanine and glutamic acid residues (KAE-rich) with high propensity to form coiled-coil structures that confers to XopD the ability to form dimers when expressed in E. coli. The full length XopD protein identified in this study (XopD1-760) displays stronger repression of the XopD plant target promoter PR1, as compared to the XopD version annotated in the public databases (XopD216-760). Furthermore, the N-terminal extension of XopD, which is absent in XopD216-760, is essential for XopD type III-dependent secretion and, therefore, for complementation of an Xcv mutant strain deleted from XopD in its ability to delay symptom development in tomato susceptible cultivars. The identification of the complete sequence of XopD opens new perspectives for future studies on the XopD protein and its virulence-associated functions in planta

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth

Exploring patterns of response across the lifespan: The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study

Background: With declining rates of participation in epidemiological studies there is an important need to attempt to understand what factors might affect response. This study examines the pattern of response at different adult ages within a contemporary cross-sectional population-based cohort, the Cambridge Centre for Ageing and Neuroscience (Cam-CAN). // Methods: Using logistic regression, we investigated associations between age, gender and Townsend deprivation level for both participants and non-participants. Weighted estimates of the odds ratios with confidence intervals for each demographic characteristic were calculated. Reasons given for refusal were grouped into three broad categories: ‘active’, ‘passive’ and illness preventing interview. // Results: An association of age and participation was found, with individuals in middle age groups more likely to participate (age group 48–57 OR: 1.8, 95% CI: 1.5–2.2 and age group 58–67 OR: 2.1, 95% CI: 1.7–2.4). Overall, there was no difference in participation between men and women. An association with deprivation was found, with those living in the most deprived areas being the least willing to participate (fifth quintile OR: 0.6, 95% CI: 0.5–0.7). An interaction between age and gender was found whereby younger women and older men were more likely to agree to participate (p = 0.01). // Conclusion: Our findings highlight some of the factors affecting recruitment into epidemiological studies in the UK and suggest that targeted age-specific recruitment strategies might be needed to increase participation rates in future cohort investigations