Cytoadherence and virulence - the case of Plasmodium knowlesi malaria.

BACKGROUND: Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36. METHODS: Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3. RESULTS: Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36. CONCLUSIONS: Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions

A Portable System with 0.1-ppm RMSE Resolution for 1-10 MHz Resonant MEMS Frequency Measurement

This article presents a portable and programmable frequency measurement system (PrO-FMS) with 0.1-ppm RMSE resolution over a measurement time interval of 33.2 s for bulk-acoustic resonator applications. PrO-FMS has a feature of choosing a frequency estimation method and accordingly the sampling frequency, which is programmable. Five frequency estimation methods, Candan, Djukanovic, Prony, M-Pisarenko, and zero crossing interpolation methods, are reviewed for high-resolution frequency measurement. PrO-FMS can also be reconfigured to select a particular resonance mode over a range of 1-10 MHz. Measurement results are provided for two different commercial quartz crystals and a microfabricated in-plane bulk acoustic resonator in two different modes of resonance. The results of these estimation methods are compared with a standard commercial tabletop frequency counter. Measurement results show that PrO-FMS can achieve a resolution of 0.1 ppm RMSE. For the same gate time, PrO-FMS provides better resolution than standard tabletop frequency counter. This article also provides a study on the behavior of the five different frequency estimation methods for short-and long-term measurements for quartz crystals and bulk acoustic resonator in two different modes

Sexual conflict over remating interval is modulated by the sex peptide pathway

Sexual conflict, in which the evolutionary interests of males and females diverge, shapes the evolution of reproductive systems across diverse taxa. Here we used the fruit fly to study sexual conflict in natural, three-way interactions comprising a female, her current and previous mates. We manipulated the potential for sexual conflict by using sex peptide receptor (SPR) null females and by varying remating from 3 to 48h, a period during which natural rematings frequently occur. SPR-lacking females do not respond to sex peptide transferred during mating and maintain virgin levels of high receptivity and low fecundity. In the absence of SPR there was a convergence of fitness interests, with all individuals gaining highest productivity at 5h remating. This suggests that the expression of sexual conflict was reduced. We observed an unexpected second male-specific advantage to early remating, resulting from an increase in the efficiency of second male sperm use. This early window of opportunity for exploitation by second males depended on the presence of SPR. The results suggest that the sex peptide pathway can modulate the expression of sexual conflict in this system, and show how variation in the selective forces that shape conflict and co-operation can be maintained

Analysis of 83mKr prompt scintillation signals in the PIXeY detector

Prompt scintillation signals from 83mKr calibration sources are a useful metric to calibrate the spatial variation of light collection efficiency and electric field magnitude of a two phase liquid-gas xenon time projection chamber. Because 83mKr decays in two steps, there are two prompt scintillation pulses for each calibration event, denoted S1a and S1b. We study the ratio of S1b to S1a signal sizes in the Particle Identification in Xenon at Yale (PIXeY) experiment and its dependence on the time separation between the two signals (Δ t), notably its increase at low Δ t. In PIXeY data, the Δ t dependence of S1b/S1a is observed to exhibit two exponential components: one with a time constant of 0.05 ± 0.02 μ s, which can be attributed to processing effects and pulse overlap and one with a time constant of 10.2 ± 2.2 μs that increases in amplitude with electric drift field, the origin of which is not yet understood

Pengaruh Pembangunan Penerapan Nilai dalam Pendidikan Abad Ke 21 Terhadap Pembentukan Sahsiah Murid Sekolah Kurang Murid (SKM) Luar Bandar di Sabah

Kajian ini dijalankan bagi mengkaji pengaruh pembangunan penerapan nilai dalam pendidikan abad ke-21 terhadap pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah. Selain itu, kajian ini mengkaji perbezaan skor min pembangunan penerapan nilai dalam pendidikan abad ke-21 dan pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah. Kajian ini menggunakan reka bentuk bukan eksperimen dan kaedah kuantitatif. Seramai 209 orang guru SKM telah dipilih untuk dijadikan sampel dalam kajian ini. Sampel ini ditentukan dengan menggunakan kaedah pensamplean rawak mudah. Instrumen soal selidik pula telah digunakan untuk memperoleh maklumat daripada sampel kajian. Data mentah yang diperoleh daripada sampel kajian dianalisis menggunakan perisian Statistical Package for Social Sciences (SPSS) dengan menggunakan analisis statistik inferensi yang melibatkan analisis Regresi Linear. Hasil analisis menunjukkan terdapat pengaruh signifikan yang positif dan kuat antara pembangunan penerapan nilai dalam pendidikan abad ke-21 terhadap pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah (Beta=0.88, t=27.65).  Hasil kajian ini diharap dapat memberikan input bermanfaat kepada pelbagai pihak khususnya Kementerian Pendidikan Malaysia dalam usaha meningkatkan kemampuan sekolah untuk melahirkan murid yang bersahsiah dan mampu memberi sumbangan kepada pembangunan negara

Association of moderate and vigorous physical activity with incidence of type 2 diabetes and subsequent mortality: 27 year follow-up of the Whitehall II study

AIMS/HYPOTHESIS: This work examined the role of physical activity in the course of diabetes using data spanning nearly three decades. Our first aim was to examine the long-term association of moderate and vigorous physical activity with incidence of type 2 diabetes. Our second aim was to investigate the association of moderate-to-vigorous physical activity post-diabetes diagnosis with subsequent risk of all-cause and cardiovascular disease mortality. METHODS: A total of 9987 participants from the Whitehall II cohort study free of type 2 diabetes at baseline (1985-1988) were followed for incidence of type 2 diabetes, based on clinical assessments between 1985 and 2016 and linkage to electronic health records up to 31 March 2017. We first examined the association of moderate and vigorous physical activity measured by questionnaire in 1985-1988 (mean age 44.9 [SD 6.0] years; women, 32.7%) with incident type 2 diabetes, using the interval-censored, illness-death model, a competing risk analysis that takes into account both competing risk of death and intermittent ascertainment of diabetes due to reliance on data collection cycles (interval-censored). The second analysis was based on individuals with type 2 diabetes over the follow-up period where we used Cox regression with inverse probability weighting to examine the association of moderate-to-vigorous physical activity after diagnosis of type 2 diabetes with risk of all-cause and cardiovascular disease mortality. RESULTS: Of the 9987 participants, 1553 developed type 2 diabetes during a mean follow-up of 27.1 (SD 6.3) years. Compared with participants who were inactive in 1985-1988, those who undertook any duration of moderate-to-vigorous physical activity had a lower risk of type 2 diabetes (HR 0.85 [95% CI 0.75, 0.97], p = 0.02; analysis adjusted for sociodemographic, behavioural and health-related factors). In 1026 participants with a diagnosis of type 2 diabetes over the follow-up period, data on moderate-to-vigorous physical activity after diabetes diagnosis were available; 165 all-cause deaths and 55 cardiovascular disease-related deaths were recorded during a mean follow-up of 8.8 (SD 6.1) years. In these participants with diabetes, any duration of moderate-to-vigorous physical activity was associated with lower all-cause mortality (HR 0.61 [95% CI 0.41, 0.93], p = 0.02) while the association with cardiovascular mortality was evident only for physical activity undertaken at or above recommendations (≥2.5 h per week of moderate-to-vigorous physical activity or ≥1.25 h per week of vigorous physical activity; HR 0.40 [95% CI 0.16, 0.96], p = 0.04) in fully adjusted models. CONCLUSIONS/INTERPRETATION: Moderate-to-vigorous physical activity plays an important role in diabetes, influencing both its incidence and prognosis. A protective effect on incidence was seen for durations of activity below recommendations and a marginal additional benefit was observed at higher durations. Among individuals with type 2 diabetes, any duration of moderate-to-vigorous physical activity was associated with reduced all-cause mortality while recommended durations of physical activity were required for protection against cardiovascular disease-related mortality. DATA AVAILABILITY: Whitehall II data, protocols and other metadata are available to the scientific community. Please refer to the Whitehall II data sharing policy at https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii/data-sharing

Bianchi Type-II String Cosmological Models in Normal Gauge for Lyra's Manifold with Constant Deceleration Parameter

The present study deals with a spatially homogeneous and anisotropic Bianchi-II cosmological models representing massive strings in normal gauge for Lyra's manifold by applying the variation law for generalized Hubble's parameter that yields a constant value of deceleration parameter. The variation law for Hubble's parameter generates two types of solutions for the average scale factor, one is of power-law type and other is of the exponential form. Using these two forms, Einstein's modified field equations are solved separately that correspond to expanding singular and non-singular models of the universe respectively. The energy-momentum tensor for such string as formulated by Letelier (1983) is used to construct massive string cosmological models for which we assume that the expansion ($\theta$) in the model is proportional to the component $\sigma^{1}_{~1}$ of the shear tensor $\sigma^{j}_{i}$. This condition leads to $A = (BC)^{m}$, where A, B and C are the metric coefficients and m is proportionality constant. Our models are in accelerating phase which is consistent to the recent observations. It has been found that the displacement vector $\beta$ behaves like cosmological term $\Lambda$ in the normal gauge treatment and the solutions are consistent with recent observations of SNe Ia. It has been found that massive strings dominate in the decelerating universe whereas strings dominate in the accelerating universe. Some physical and geometric behaviour of these models are also discussed.Comment: 24 pages, 10 figure

Hubungan antara Pembangunan Penerapan Nilai dalam Pendidikan Abad Ke-21 dengan Pembentukan Sahsiah Murid Sekolah Kurang Murid (SKM) Luar Bandar di Sabah

Penerapan nilai dalam pendidikan abad ke-21 amat penting bagi membentuk sahsiah murid yang mapan dalam pelbagai aspek seperti yang digariskan dalam Falsafah pendidikan Kebangsaan (FPK). Kajian korelasi ini dijalankan bagi mengkaji hubungan pembangunan penerapan nilai dalam pendidikan abad ke-21 dengan pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah. Kajian ini menggunakan reka bentuk bukan eksperimen dan kaedah kuantitatif. Seramai 209 orang guru SKM dijadikan sampel dalam kajian ini yang dipilih menggunakan kaedah pensamplean rawak mudah. Instrumen soal selidik pula digunakan bagi mengukur variabel-variabel kajian. Data mentah dianalisis menggunakan perisian Statistical Package for Social Sciences (SPSS) dengan menggunakan analisis statistik inferensi yang melibatkan ujian Korelasi Pearson. Hasil analisis menunjukkan terdapat hubungan positif signifikan yang kuat antara pembangunan penerapan nilai dalam pendidikan abad ke-21 dengan pembentukan sahsiah murid Sekolah Kurang Murid (SKM) luar bandar di Sabah (r=0.88, P<0.05). Dapatan kajian ini memberi maklumat berguna berkaitan dengan penerapan nilai dalam pendidikan abad ke-21 dan pembentukan sahsiah murid yang diharap dapat memberikan sumbangan ke arah memperkasakan sistem pendidikan kebangsaan

Adiposity, obesity, and arterial aging: longitudinal study of aortic stiffness in the Whitehall II cohort

We sought to determine whether adiposity in later midlife is an independent predictor of accelerated stiffening of the aorta. Whitehall II study participants (3789 men; 1383 women) underwent carotid-femoral applanation tonometry at the mean age of 66 and again 4 years later. General adiposity by body mass index, central adiposity by waist circumference and waist:hip ratio, and fat mass percent by body impedance were assessed 5 years before and at baseline. In linear mixed models adjusted for age, sex, ethnicity, and mean arterial pressure, all adiposity measures were associated with aortic stiffening measured as increase in pulse wave velocity (PWV) between baseline and follow-up. The associations were similar in the metabolically healthy and unhealthy, according to Adult Treatment Panel-III criteria excluding waist circumference. C-reactive protein and interleukin-6 levels accounted for part of the longitudinal association between adiposity and PWV change. Adjusting for chronic disease, antihypertensive medication and risk factors, standardized effects of general and central adiposity and fat mass percent on PWV increase (m/s) were similar (0.14, 95% confidence interval: 0.05-0.24, P=0.003; 0.17, 0.08-0.27, P<0.001; 0.14, 0.05-0.22, P=0.002, respectively). Previous adiposity was associated with aortic stiffening independent of change in adiposity, glycaemia, and lipid levels across PWV assessments. We estimated that the body mass index-linked PWV increase will account for 12% of the projected increase in cardiovascular risk because of high body mass index. General and central adiposity in later midlife were strong independent predictors of aortic stiffening. Our findings suggest that adiposity is an important and potentially modifiable determinant of arterial aging