ALBERT

Description: N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics, including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activity (i.e., effector function or serum half-life). In particular, attention has focused on engineering processes in vivo or in vitro to alter the structure of the N-glycosylation of the Fc region of anti-cancer monoclonal antibodies in order to increase antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we applied the mannosidase I inhibitor kifunensine to the Nicotiana benthamiana transient expression platform to produce an afucosylated anti-CD20 antibody (rituximab). We determined the optimal concentration of kifunensine used in the infiltration solution, 0.375 µM, which was sufficient to produce exclusively oligomannose glycoforms, at a concentration 14 times lower than previously published levels. The resulting afucosylated rituximab revealed a 14-fold increase in ADCC activity targeting the lymphoma cell line Wil2-S when compared with rituximab produced in the absence of kifunensine. When applied to the cost-effective and scalable N. benthamiana transient expression platform, the use of kifunensine allows simple in-process glycan engineering without the need for transgenic hosts.

Description: Ultrasonic Guided-wave (UGW) testing of pipelines allows long-range assessment of pipe integrity from a single point of inspection. This technology uses a number of arrays of transducers separated by a distance from each other to generate a single axisymmetric (torsional) wave mode. The location of anomalies in the pipe is determined by inspectors using the received signal. Guided-waves are multimodal and dispersive. In practical tests, nonaxisymmetric waves are also received due to the nonideal testing conditions, such as presence of variable transfer function of transducers. These waves are considered as the main source of noise in the guided-wave inspection of pipelines. In this paper, we propose a method to exploit the differences in the power spectrum of the torsional wave and flexural waves, in order to detect the torsional wave, leading to the defect location. The method is based on a sliding moving window, where in each iteration the signals are normalised and their power spectra are calculated. Each power spectrum is compared with the previously known spectrum of excitation sequence. Five binary conditions are defined; all of these need to be met in order for a window to be marked as defect signal. This method is validated using a synthesised test case generated by a Finite Element Model (FEM) as well as real test data gathered from laboratory trials. In laboratory trials, three different pipes with defects sizes of 4%, 3% and 2% cross-sectional area (CSA) material loss were evaluated. In order to find the optimum frequency, the varying excitation frequency of 30 to 50 kHz (in steps of 2 kHz) were used. The results demonstrate the capability of this algorithm in detecting torsional waves with low signal-to-noise ratio (SNR) without requiring any change in the excitation sequence. This can help inspectors by validating the frequency response of the received sequence and give more confidence in the detection of defects in guided-wave testing of pipelines.

Description: Ultrasonic guided wave (UGW) testing of pipelines allows long range assessments of pipe integrity from a single point of inspection. This technology uses a number of arrays of transducers, linearly placed apart from each other to generate a single axisymmetric wave mode. The general propagation routine of the device results in a single time domain signal, which is then used by the inspectors to detect the axisymmetric wave for any defect location. Nonetheless, due to inherited characteristics of the UGW and non-ideal testing conditions, non-axisymmetric (flexural) waves will be transmitted and received in the tests. This adds to the complexity of results’ interpretation. In this paper, we implement an adaptive leaky normalized least mean square (NLMS) filter for reducing the effect of non-axisymmetric waves and enhancement of axisymmetric waves. In this approach, no modification in the device hardware is required. This method is validated using the synthesized signal generated by a finite element model (FEM) and real test data gathered from laboratory trials. In laboratory trials, six different sizes of defects with cross-sectional area (CSA) material loss of 8% to 3% (steps of 1%) were tested. To find the optimum frequency, several excitation frequencies in the region of 30–50 kHz (steps of 2 kHz) were used. Furthermore, two sets of parameters were used for the adaptive filter wherein the first set of tests the optimum parameters were set to the FEM test case and, in the second set of tests, the data from the pipe with 4% CSA defect was used. The results demonstrated the capability of this algorithm for enhancing a defect’s signal-to-noise ratio (SNR).

Description: X-ray time lags are complicated in nature. The exact reasons for complex lag spectra are as yet unknown. However, the hard lags, in general, are believed to be originated due to inverse Comptonization process. However, the origin of soft lags remained mischievous. Recent studies on “Disk–Jet Connections” revealed that the jets are also contributing in the X-ray spectral and timing properties in a magnitude which was more than what was predicted earlier. In this article, we first show an exact anticorrelation between X-ray time lag and radio flux for XTE J1550-546 during its 1998 outburst. We propose that the soft lags might be generated due to the change in the accretion disk structure along the line of sight during higher jet activity.

Description: Gullies are significant contributors of sediment to streams in the southeastern USA. This study investigated gully erosion in the clay-rich soils of east Tennessee under a humid subtropical climate. The aims of this study were to (1) estimate long-term erosion rates for different gully geomorphic settings, (2) compare patterns of erosion for the different settings, and (3) model the response of gully erosion to freeze-thaw events. Erosion was measured weekly from June 2012 to August 2018 using 105 erosion pins distributed in gully channels, interfluves, and sidewalls. Erosion rates were estimated from average slopes of lines of best fit of pin lengths versus time. Maximum and minimum temperature was calculated daily using an on-site weather station and freeze-thaw events were identified. Gully erosion was modeled using antecedent freeze-thaw activity for the three geomorphic settings. Long-term erosion rates in channels, interfluves, and sidewalls were 2.5 mm/year, 20 mm/year, and 21 mm/year, respectively; however, week-by-week erosion was statistically different between the three settings, indicating different erosive drivers. Models of erosion with lagged freeze-thaw variables explained up to 34.8% of the variability in erosion variables; sidewall erosion was most highly related to freeze-thaw activity. Freeze-thaw in prior weeks was an important variable in all erosion models.

Description: Development requires the careful orchestration of several biological events in order to create any structure and, eventually, to build an entire organism. On the other hand, the fate transformation of terminally differentiated cells is a consequence of erroneous development, and ultimately leads to cancer. In this review, we elaborate how development and cancer share several biological processes, including molecular controls. Transcription factors (TF) are at the helm of both these processes, among many others, and are evolutionarily conserved, ranging from yeast to humans. Here, we discuss four families of TFs that play a pivotal role and have been studied extensively in both embryonic development and cancer—high mobility group box (HMG), GATA, paired box (PAX) and basic helix-loop-helix (bHLH) in the context of their role in development, cancer, and their conservation across several species. Finally, we review TFs as possible therapeutic targets for cancer and reflect on the importance of natural resistance against cancer in certain organisms, yielding knowledge regarding TF function and cancer biology.

Description: Obesity-related conditions impose a considerable and growing burden on low- and middle-income countries, including South Africa. We aimed to assess the effect of twice a 10-week multidimensional, school-based physical activity intervention on children’s health in Port Elizabeth, South Africa. A cluster-randomised controlled trial was implemented from February 2015 to May 2016 in grade 4 classes in eight disadvantaged primary schools. Interventions consisted of physical education lessons, moving-to-music classes, in-class activity breaks and school infrastructure enhancement to promote physical activity. Primary outcomes included cardiorespiratory fitness, body mass index (BMI) and skinfold thickness. Explanatory variables were socioeconomic status, self-reported physical activity, stunting, anaemia and parasite infections. Complete data were available from 746 children. A significantly lower increase in the mean BMI Z-score (estimate of difference in mean change: −0.17; 95% confidence interval (CI): −0.24 to −0.09; p 〈 0.001) and reduced increase in the mean skinfold thickness (difference in mean change: −1.06; 95% CI: −1.83 to −0.29; p = 0.007) was observed in intervention schools. No significant group difference occurred in the mean change of cardiorespiratory fitness (p 〉 0.05). These findings show that a multidimensional, school-based physical activity intervention can reduce the increase in specific cardiovascular risk factors. However, a longer and more intensive intervention might be necessary to improve cardiorespiratory fitness.