Delay Learning Architectures for Memory and Classification

We present a neuromorphic spiking neural network, the DELTRON, that can remember and store patterns by changing the delays of every connection as opposed to modifying the weights. The advantage of this architecture over traditional weight based ones is simpler hardware implementation without multipliers or digital-analog converters (DACs) as well as being suited to time-based computing. The name is derived due to similarity in the learning rule with an earlier architecture called Tempotron. The DELTRON can remember more patterns than other delay-based networks by modifying a few delays to remember the most 'salient' or synchronous part of every spike pattern. We present simulations of memory capacity and classification ability of the DELTRON for different random spatio-temporal spike patterns. The memory capacity for noisy spike patterns and missing spikes are also shown. Finally, we present SPICE simulation results of the core circuits involved in a reconfigurable mixed signal implementation of this architecture.Comment: 27 pages, 20 figure

Home delivery complicated with puerperal sepsis in urban India

Puerperal sepsis is among the leading and preventable causes of maternal morbidity and mortality worldwide and especially in developing countries. We report an interesting case of home delivery complicated with puerperal sepsis, who required obstetric hysterectomy. Inspite of being a resident of an urban metropolitan city patient had no access to antepartum, intrapartum or even postpartum care. She presented on day eleven postpartum to our institute by which time, her condition had progressed to frank pyoperitoneum and severe anaemia. Urgent, aggressive intervention in the form of evacuation of intra-abdominal pus, obstetric hysterectomy with oophorectomy saved her life

Tripartite analysis across business cycles in Turkey: A multi-timescale inquiry of efficiency, volatility and integration

AbstractIn the current era of globalization, deregulation and liberalization of markets have led to financial integration amongst developing and developed countries. The sudden massive inflow of capital into developing country's stock markets begs the question of whether or not the markets are sufficiently efficient to handle the increasing integration of markets. Furthermore, the relationship between the integration and efficiency of stock markets tends to be of greater importance during economic downturns. Taking Turkey as a case study owing to its economic growth and importance in two successful blocs, i.e. the EU and the OIC, we attempt to analyse the linkages between stock market efficiency and integration during the different phases of the economy. The findings of our study provide an interesting insight into the relative improvement in volatility, efficiency and integration across business cycles, in a multi time scale analysis

Potential Role of Ultrafine Particles in Associations between Airborne Particle Mass and Cardiovascular Health

Numerous epidemiologic time-series studies have shown generally consistent associations of cardiovascular hospital admissions and mortality with outdoor air pollution, particularly mass concentrations of particulate matter (PM) ≤2.5 or ≤10 μm in diameter (PM(2.5), PM(10)). Panel studies with repeated measures have supported the time-series results showing associations between PM and risk of cardiac ischemia and arrhythmias, increased blood pressure, decreased heart rate variability, and increased circulating markers of inflammation and thrombosis. The causal components driving the PM associations remain to be identified. Epidemiologic data using pollutant gases and particle characteristics such as particle number concentration and elemental carbon have provided indirect evidence that products of fossil fuel combustion are important. Ultrafine particles < 0.1 μm (UFPs) dominate particle number concentrations and surface area and are therefore capable of carrying large concentrations of adsorbed or condensed toxic air pollutants. It is likely that redox-active components in UFPs from fossil fuel combustion reach cardiovascular target sites. High UFP exposures may lead to systemic inflammation through oxidative stress responses to reactive oxygen species and thereby promote the progression of atherosclerosis and precipitate acute cardiovascular responses ranging from increased blood pressure to myocardial infarction. The next steps in epidemiologic research are to identify more clearly the putative PM casual components and size fractions linked to their sources. To advance this, we discuss in a companion article (Sioutas C, Delfino RJ, Singh M. 2005. Environ Health Perspect 113:947–955) the need for and methods of UFP exposure assessment

Knowledge and practice of folic acid supplementation and impact of income level on awareness among women of child-bearing age in Saudi Arabia

Purpose: To investigate the knowledge of Saudi women (pregnant and non-pregnant) about the significance of folic acid (FA) supplementation and to determine how income levels affects this knowledge and its implementation. Methods: The study was conducted among women of child-bearing age attending Al-Hada Armed Forces Hospital and Khaliss General Hospital (both in Riyadh, Saudi Arabia) for pregnant women and Omm Al-Qura University in Makkah Governorate (Saudi Arabia) for non-pregnant women. A structured questionnaire was used to collect socio-demographic data and to analyze levels of FA knowledge, including general awareness, proper timing of its use, information source, FA benefits, and the perils of FA deficiency. A chi-square test was performed to test the differences between variables. Results: Analysis of the survey data revealed that 81.1 % of non–pregnant and 91.1 % of pregnant women were aware of the term, FA (p &lt; 0.05). Moreover, 71.1 % of the pregnant compared to 35.6% of non-pregnant women knew that this supplement must be taken before becoming pregnant and this difference was statistically significant (p &lt; 0.05). For pregnant women, doctors and previous pregnancies were the main sources of FA knowledge, while mass media was the most frequently reported source for non-pregnant women (p &lt; 0.05). Income level was not associated with FA knowledge in either group. Conclusions: This study illustrates a deficiency in the knowledge and consumption of this important micronutrient in women of childbearing age, the population most in need of this information. Nutrition education should be provided to increase the understanding and practice of FA supplementation periconceptionally and during pregnancy

Monocyte Function in Parkinson's Disease and the Impact of Autologous Serum on Phagocytosis.

Background: Increasing evidence implicates involvement of the innate immune system in the initiation and progression of Parkinson's disease (PD). Monocytes and monocyte-derived cells perform a number of functions, such as phagocytosis, chemotaxis, and cytokine secretion, which may be particularly relevant to PD pathology. The behavior of these cells in early-moderate disease, in conditions more similar to the in-vivo environment has not been fully evaluated. Research Question: Does monocyte function, including phagocytosis, chemotaxis and cytokine secretion, differ in early-moderate PD compared to age and gender-matched controls? Methods: Participants included PD patients (n = 41) with early-moderate stage disease (Hoehn and Yahr ≤2) and age and gender matched controls (n = 41). Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and monocytes were further separated using CD14 magnetic beads. Functional assays, including bead phagocytosis (in standard medium and autologous serum), Boyden chamber trans-well chemotaxis, and cytokine secretion on lipopolysaccharide stimulation were performed. Monocyte surface markers relating to chemotaxis were measured using immunohistochemistry and flow cytometry. Between-group analysis was performed using paired t-tests. Results: An autologous serum environment significantly increased bead phagocytosis compared to standard medium as expected, in both patients and controls. When in autologous serum, PD monocytes demonstrated enhanced phagocytosis compared to control monocytes (p = 0.029). The level of serum-based phagocytosis was influenced by complement inactivation and the origin of the serum. There were no significant differences between PD and controls in terms of standard medium based monocyte migration or cytokine secretion in this cohort. Conclusions: Autologous serum has a significant influence on monocyte phagocytosis and reveals increased phagocytic capacity in early-moderate PD compared to controls. These conditions may better reflect the function of monocytes in-vivo in PD patients than standard medium based phagocytosis assays. Further studies will be required to replicate these results in larger cohorts, including earlier and later stages of disease, and to understand which serum factors are responsible for this observation and the potential mechanistic relevance to PD pathogenesis.Funding for this work was provided by Addenbrooke’s Charitable Trust, the Rosetrees Trust and the NIHR Cambridge Biomedical Research Centre. RSW was supported by a Fellowship from Addenbrooke’s Charitable Trust. DKV is supported by a Junior Research Fellowship from Homerton College, Cambridge. KMS is supported by a Fellowship from the Wellcome Trust. CHWG is supported by a Clinician Scientist Fellowship from the Medical Research Council. RAB is an NIHR Senior Investigator and is supported by the Wellcome Trust-MRC Cambridge Stem Cell Institute

Potato NPH3/RPT2-like protein StNRL1, targeted by a Phytophthora infestans RXLR effector, is a susceptibility factor

Plant pathogens deliver effectors to manipulate host processes. We know little about how fungal and oomycete effectors target host proteins to promote susceptibility, yet such knowledge is vital to understand crop disease. We show that either transient expression in Nicotiana benthamiana, or stable transgenic expression in potato (Solanum tuberosum), of the Phytophthora infestans RXLR effector Pi02860 enhances leaf colonization by the pathogen. Expression of Pi02860 also attenuates cell death triggered by the P. infestans microbe-associated molecular pattern INF1, indicating that the effector suppresses pattern-triggered immunity. However, the effector does not attenuate cell death triggered by Cf4/Avr4 coexpression, showing that it does not suppress all cell death activated by cell surface receptors. Pi02860 interacts in yeast two-hybrid assays with potato NPH3/RPT2-LIKE1 (NRL1), a predicted CULLIN3-associated ubiquitin E3 ligase. Interaction of Pi02860 in planta was confirmed by coimmunoprecipitation and bimolecular fluorescence complementation assays. Virus-induced gene silencing of NRL1 in N. benthamiana resulted in reduced P. infestans colonization and accelerated INF1-mediated cell death, indicating that this host protein acts as a negative regulator of immunity. Moreover, whereas NRL1 virus-induced gene silencing had no effect on the ability of the P. infestans effector Avr3a to suppress INF1-mediated cell death, such suppression by Pi02860 was significantly attenuated, indicating that this activity of Pi02860 is mediated by NRL1. Transient overexpression of NRL1 resulted in the suppression of INF1-mediated cell death and enhanced P. infestans leaf colonization, demonstrating that NRL1 acts as a susceptibility factor to promote late blight disease

Peripheral innate immune and bacterial signals relate to clinical heterogeneity in Parkinson's disease.

The innate immune system is implicated in Parkinson's disease (PD), but peripheral in-vivo clinical evidence of the components and driving mechanisms involved and their relationship with clinical heterogeneity and progression to dementia remain poorly explored. We examined changes in peripheral innate immune-related markers in PD cases (n = 41) stratified according to risk of developing early dementia. 'Higher Risk'(HR) (n = 23) and 'Lower Risk' (LR) (n = 18) groups were defined according to neuropsychological predictors and MAPT H1/H2 genotype, and compared to age, gender and genotype-matched controls. Monocyte subsets and expression of key surface markers were measured using flow cytometry. Serum markers including alpha-synuclein, inflammasome-related caspase-1 and bacterial translocation-related endotoxin were measured using quantitative immuno-based assays. Specific markers were further investigated using monocyte assays and validated in plasma samples from a larger incident PD cohort (n = 95). We found that classical monocyte frequency was elevated in PD cases compared to controls, driven predominantly by the HR group, in whom Toll-Like Receptor (TLR)4+ monocytes and monocyte Triggering Receptor Expressed on Myeloid cells-2 (TREM2) expression were also increased. Monocyte Human Leukocyte Antigen (HLA)-DR expression correlated with clinical variables, with lower levels associated with worse cognitive/motor performance. Notably, monocyte changes were accompanied by elevated serum bacterial endotoxin, again predominantly in the HR group. Serum alpha-synuclein and inflammasome-related caspase-1 were decreased in PD cases compared to controls regardless of group, with decreased monocyte alpha-synuclein secretion in HR cases. Further, alpha-synuclein and caspase-1 correlated positively in serum and monocyte lysates, and in plasma from the larger cohort, though no associations were seen with baseline or 36-month longitudinal clinical data. Principal Components Analysis of all monocyte and significant serum markers indicated 3 major components. Component 1 (alpha-synuclein, caspase-1, TLR2+ monocytes) differentiated PD cases and controls in both groups, while Component 2 (endotoxin, monocyte TREM2, alpha-synuclein) did so predominantly in the HR group. Component 3 (classical monocytes, alpha-synuclein) also differentiated cases and controls overall in both groups. These findings demonstrate that systemic innate immune changes are present in PD and are greatest in those at higher risk of rapid progression to dementia. Markers associated with PD per-se (alpha-synuclein, caspase-1), differ from those related to cognitive progression and clinical heterogeneity (endotoxin, TREM2, TLR4, classical monocytes, HLA-DR), with mechanistic and therapeutic implications. Alpha-synuclein and caspase-1 are associated, suggesting inflammasome involvement common to all PD, while bacterial translocation associated changes may contribute towards progression to Parkinson's dementia. Additionally, HLA-DR-associated variations in antigen presentation/clearance may modulate existing clinical disease