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A 200-256-GS/s current-mode 4-way interleaved sampling front-end with over 67-GHz bandwidth using a slew-rate insensitive clocking scheme
No full textThe surge of data traffic in emerging optical communication applications has led to the development of ultra-fast transceivers with extremely high data throughput. The latest transmitters and receivers aim for symbol rates of 150-200 Gbaud or even higher, striving to achieve band-widths beyond 70 GHz. However, the current state-of-the-artanalog-to-digital converters (ADCs) in advanced CMOS-FinFET technologies can only handle limited analog input bandwidths and sampling rates, becoming a bottleneck in enhancing the overall speed of the transceiver. A time-interleaved sampling front-end acting as an input signal de-interleaver can reduce the sub-ADCs' analog bandwidth and clock jitter requirements. This article investigates a current-mode time-interleaved 1-4 sampling front-end operating at 200-256 GS/s, using a 50% duty-cycle slew-rate insensitive quadrature clocking strategy. The chip was fabricated in a 130-nm SiGe BiCMOS technology and was characterized by single-tone sinusoidal and non-return-to-zero/pulse-amplitude- modulation-4-level (NRZ/PAM-4)measurements at 200, 224, and 256 GS/s. The chip demonstratesa 3-dB analog input bandwidth beyond 67 GHz and a signal-to-noise-and-distortion ratio (SNDR) of 27.8-34.1 dB (at 200 GS/s),25-36.3 dB (at 224 GS/s), and 22.3-39 dB (at 256 GS/s) for input frequencies from 1.1 to 67.1 GHz. The analog demultiplexing functionality of the sampling front-end is demonstrated with 100,112, and 128 Gbaud NRZ/PAM-4 measurements. The completechip consumes a power of 1.1 W at 256 GS/s, corresponding to an efficiency of 4.3 pJ/sample or 4.3 pJ/bit (with two samplesper symbol).The surge of data traffic in emerging optical communication applications has led to the development of ultra-fast transceivers with extremely high data throughput. The latest transmitters and receivers aim for symbol rates of 150-200 Gbaud or even higher, striving to achieve band-widths beyond 70 GHz. However, the current state-of-the-artanalog-to-digital converters (ADCs) in advanced CMOS-FinFET technologies can only handle limited analog input bandwidths and sampling rates, becoming a bottleneck in enhancing the overall speed of the transceiver. A time-interleaved sampling front-end acting as an input signal de-interleaver can reduce the sub-ADCs' analog bandwidth and clock jitter requirements. This article investigates a current-mode time-interleaved 1-4 sampling front-end operating at 200-256 GS/s, using a 50% duty-cycle slew-rate insensitive quadrature clocking strategy. The chip was fabricated in a 130-nm SiGe BiCMOS technology and was characterized by single-tone sinusoidal and non-return-to-zero/pulse-amplitude- modulation-4-level (NRZ/PAM-4)measurements at 200, 224, and 256 GS/s. The chip demonstratesa 3-dB analog input bandwidth beyond 67 GHz and a signal-to-noise-and-distortion ratio (SNDR) of 27.8-34.1 dB (at 200 GS/s),25-36.3 dB (at 224 GS/s), and 22.3-39 dB (at 256 GS/s) for input frequencies from 1.1 to 67.1 GHz. The analog demultiplexing functionality of the sampling front-end is demonstrated with 100,112, and 128 Gbaud NRZ/PAM-4 measurements. The completechip consumes a power of 1.1 W at 256 GS/s, corresponding to an efficiency of 4.3 pJ/sample or 4.3 pJ/bit (with two samplesper symbol).A
A guide to germ-free and gnotobiotic mouse technology to study health and disease
No full textThe intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research. Germ-free and gnotobiotic mouse technology allows the unraveling of complex host-microbiota interactions within a reductionist framework. The implementation of these methodologies poses significant technical and experimental challenges. This review explores practical insights aimed at enhancing the precision and success of germ-free and gnotobiotic experiments. imageThe intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research. Germ-free and gnotobiotic mouse technology allows the unraveling of complex host-microbiota interactions within a reductionist framework. The implementation of these methodologies poses significant technical and experimental challenges. This review explores practical insights aimed at enhancing the precision and success of germ-free and gnotobiotic experiments. imageA
Tijdschriften als dynamische knooppunten van naoorlogse vernieuwingsdrang : een analyse van het netwerk van De Stem en de relatie tot Ter Waarheid (1921-1924)
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History’s view on the principal–agent relationship : including history, context and change : evidence from three historical cases in the Southern Netherlands
No full textPurpose: The principal-agent literature often draws criticism for its ahistorical, acontextual and static nature, particularly when theories such as the agency or the stewardship theory are being used. This is because the field of economics tends to develop universalistic models and theories, excluding history, context and change, which renders them unusable for practitioners whose behavior is (partially) guided by the complex and differing environments in which they find themselves. The purpose of this paper is to contribute to this criticism by investigating how (and if) history, context and change influence the principal-agent relationship.Design/methodology/approach: Instead of using the typical economic methodologies to study the principal-agent relationship, this paper makes use of the methodologies of the field of history to investigate how history, context and change affect principal-agent relationships in three cases in the early modern Southern Netherlands (the Dukes of Arenberg, the Roosewalle farm and Abbot De Loose of the Abbey of Ename). This methodology is especially suited, as it results in historical narratives that incorporate all of these three elements.Findings: The main finding is that the cases show how history, context and change clearly affect the principal-agent relationship. These aspects are intricately intertwined, as earlier choices and context can cause a change in the principal-agent relationship, this creates a new presence (with an altered history) and sometimes even a new context. This results in a highly dynamic relationship that can evolve in very short periods, mostly in a path-dependent manner.Research limitations/implications: The paper advocates by example for a shift in principal-agent research, emphasizing the necessity of considering history, context and change. This study demonstrates that these factors greatly affect the nature of the principal-agent relationship. In doing so, it may provide practitioners with better insights, as real-world principal-agent relationships are indeed impacted by these three factors.Originality/value: By using historical methods, this study shows for the first time how context, change and history indeed influence principal-agent relationships. The findings of this paper encourage the development of theories and theoretical frameworks that more closely resemble reality, rather than being universalistic.Purpose: The principal-agent literature often draws criticism for its ahistorical, acontextual and static nature, particularly when theories such as the agency or the stewardship theory are being used. This is because the field of economics tends to develop universalistic models and theories, excluding history, context and change, which renders them unusable for practitioners whose behavior is (partially) guided by the complex and differing environments in which they find themselves. The purpose of this paper is to contribute to this criticism by investigating how (and if) history, context and change influence the principal-agent relationship.Design/methodology/approach: Instead of using the typical economic methodologies to study the principal-agent relationship, this paper makes use of the methodologies of the field of history to investigate how history, context and change affect principal-agent relationships in three cases in the early modern Southern Netherlands (the Dukes of Arenberg, the Roosewalle farm and Abbot De Loose of the Abbey of Ename). This methodology is especially suited, as it results in historical narratives that incorporate all of these three elements.Findings: The main finding is that the cases show how history, context and change clearly affect the principal-agent relationship. These aspects are intricately intertwined, as earlier choices and context can cause a change in the principal-agent relationship, this creates a new presence (with an altered history) and sometimes even a new context. This results in a highly dynamic relationship that can evolve in very short periods, mostly in a path-dependent manner.Research limitations/implications: The paper advocates by example for a shift in principal-agent research, emphasizing the necessity of considering history, context and change. This study demonstrates that these factors greatly affect the nature of the principal-agent relationship. In doing so, it may provide practitioners with better insights, as real-world principal-agent relationships are indeed impacted by these three factors.Originality/value: By using historical methods, this study shows for the first time how context, change and history indeed influence principal-agent relationships. The findings of this paper encourage the development of theories and theoretical frameworks that more closely resemble reality, rather than being universalistic.A
Minimal adherence threshold to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation to reduce the risk of thromboembolism and death : a nationwide cohort study
No full textPurpose Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks.Methods Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes.Results 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and < 80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90-94% versus 100% (aHR 1.09, 95%CI (1.01-1.17)). Findings were similar with once-daily and twice-daily dosed NOACs.Conclusion Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be & GE; 90%, preferably even & GE; 95%.Purpose Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks.Methods Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes.Results 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and < 80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90-94% versus 100% (aHR 1.09, 95%CI (1.01-1.17)). Findings were similar with once-daily and twice-daily dosed NOACs.Conclusion Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be & GE; 90%, preferably even & GE; 95%.A
Division zone activity determines the potential of drought‐stressed maize leaves to resume growth after rehydration
No full textDrought is one of the most devastating causes of yield losses in crops like maize, and the anticipated increases in severity and duration of drought spells due to climate change pose an imminent threat to agricultural productivity. To understand the drought response, phenotypic and molecular studies are typically performed at a given time point after drought onset, representing a steady-state adaptation response. Because growth is a dynamic process, we monitored the drought response with high temporal resolution and examined cellular and transcriptomic changes after rehydration at 4 and 6 days after leaf four appearance. These data showed that division zone activity is a determinant for full organ growth recovery upon rehydration. Moreover, a prolonged maintenance of cell division by the ectopic expression of PLASTOCHRON1 extends the ability to resume growth after rehydration. The transcriptome analysis indicated that GROWTH-REGULATING FACTORS (GRFs) affect leaf growth by impacting cell division duration, which was confirmed by a prolonged recovery potential of the GRF1-overexpression line after rehydration. Finally, we used a multiplex genome editing approach to evaluate the most promising differentially expressed genes from the transcriptome study and as such narrowed down the gene space from 40 to seven genes for future functional characterization.Drought is one of the most devastating causes of yield losses in crops like maize, and the anticipated increases in severity and duration of drought spells due to climate change pose an imminent threat to agricultural productivity. To understand the drought response, phenotypic and molecular studies are typically performed at a given time point after drought onset, representing a steady-state adaptation response. Because growth is a dynamic process, we monitored the drought response with high temporal resolution and examined cellular and transcriptomic changes after rehydration at 4 and 6 days after leaf four appearance. These data showed that division zone activity is a determinant for full organ growth recovery upon rehydration. Moreover, a prolonged maintenance of cell division by the ectopic expression of PLASTOCHRON1 extends the ability to resume growth after rehydration. The transcriptome analysis indicated that GROWTH-REGULATING FACTORS (GRFs) affect leaf growth by impacting cell division duration, which was confirmed by a prolonged recovery potential of the GRF1-overexpression line after rehydration. Finally, we used a multiplex genome editing approach to evaluate the most promising differentially expressed genes from the transcriptome study and as such narrowed down the gene space from 40 to seven genes for future functional characterization.A
Well-being policies and applicant attraction : the mediating role of employer brand personality
No full textIncreasingly, (potential) employees take their well-being into account when choosing or quitting jobs. However, we do not yet know whether and how organizations can influence applicant attraction by communicating their well-being policy within recruitment materials. Based on signaling theory, we hypothesize that a well-being policy functions as a signal through which potential applicants make inferences about employer brand personality (organizational warmth and competence), ultimately increasing organizational attractiveness and application intentions. Moreover, we examine whether the content of the well-being policy matters and compare (a) prevention versus promotion policies and (b) individual-level versus organizational-level policies. Two experimental studies among samples of Belgian employed potential applicants showed that a well-being policy increased organizational attractiveness and application intentions, while organizational warmth served as an explaining mechanism. Organizational-level well-being policies elicited higher application intentions compared to individual-level well-being policies, which was mediated by organizational warmth and competence. Moreover, we found that even in the presence of another strong signal (salary information), a well-being policy is still linked to increased applicant attraction. Lastly, a well-being policy increases organizational attractiveness especially when salary is average in comparison to when salary is above average.Increasingly, (potential) employees take their well-being into account when choosing or quitting jobs. However, we do not yet know whether and how organizations can influence applicant attraction by communicating their well-being policy within recruitment materials. Based on signaling theory, we hypothesize that a well-being policy functions as a signal through which potential applicants make inferences about employer brand personality (organizational warmth and competence), ultimately increasing organizational attractiveness and application intentions. Moreover, we examine whether the content of the well-being policy matters and compare (a) prevention versus promotion policies and (b) individual-level versus organizational-level policies. Two experimental studies among samples of Belgian employed potential applicants showed that a well-being policy increased organizational attractiveness and application intentions, while organizational warmth served as an explaining mechanism. Organizational-level well-being policies elicited higher application intentions compared to individual-level well-being policies, which was mediated by organizational warmth and competence. Moreover, we found that even in the presence of another strong signal (salary information), a well-being policy is still linked to increased applicant attraction. Lastly, a well-being policy increases organizational attractiveness especially when salary is average in comparison to when salary is above average.A
Can approach-avoidance instructions influence facial representations? A distinction between past- and future-oriented inferences
No full textMere instructions about a supposedly upcoming approach/avoidance training (i.e., "you will approach stimulus A and avoid stimulus B") can influence stimuli evaluation (e.g., stimulus A is evaluated more positively). In this work, we argue that because approach/avoidance instructions are typically future-oriented (e.g., "you will approach stimulus A"), they are less powerful than past-oriented information (e.g., "you approached stimulus A"). We introduce the placebo approach/avoidance training, a procedure implementing past-oriented information that involves a bogus training without actual contingencies between stimuli and approach/avoidance actions. Experiments 1a and 1b revealed an approach/avoidance effect on visual representations when employing placebo training. Experiment 2 showed that the effect of placebo training (involving past-oriented information) is larger than the effect of approach/avoidance instructions (involving future-oriented information). Finally, Experiment 3 replicated the distinct effect of past- vs. future-oriented approach/avoidance information by controlling for the experience of approaching/avoiding stimuli. This work highlights the role of past-oriented thinking in approach/avoidance effects.Mere instructions about a supposedly upcoming approach/avoidance training (i.e., "you will approach stimulus A and avoid stimulus B") can influence stimuli evaluation (e.g., stimulus A is evaluated more positively). In this work, we argue that because approach/avoidance instructions are typically future-oriented (e.g., "you will approach stimulus A"), they are less powerful than past-oriented information (e.g., "you approached stimulus A"). We introduce the placebo approach/avoidance training, a procedure implementing past-oriented information that involves a bogus training without actual contingencies between stimuli and approach/avoidance actions. Experiments 1a and 1b revealed an approach/avoidance effect on visual representations when employing placebo training. Experiment 2 showed that the effect of placebo training (involving past-oriented information) is larger than the effect of approach/avoidance instructions (involving future-oriented information). Finally, Experiment 3 replicated the distinct effect of past- vs. future-oriented approach/avoidance information by controlling for the experience of approaching/avoiding stimuli. This work highlights the role of past-oriented thinking in approach/avoidance effects.A
Tree smoothing : post-hoc regularization of tree ensembles for interpretable machine learning
No full textRandom Forests (RFs) are powerful ensemble learning algorithms that are widely used in various machine learning tasks. However, they tend to overfit noisy or irrelevant features, which can result in decreased generalization performance. Post-hoc regularization techniques aim to solve this problem by modifying the structure of the learned ensemble after training. We propose a novel post-hoc regularization via tree smoothing for classification tasks to leverage the reliable class distributions closer to the root node whilst reducing the impact of more specific and potentially noisy splits deeper in the tree. Our novel approach allows for a form of pruning that does not alter the general structure of the trees, adjusting the influence of nodes based on their proximity to the root node. We evaluated the performance of our method on various machine learning benchmark data sets and on cancer data from The Cancer Genome Atlas (TCGA). Our approach demonstrates competitive performance compared to the state-of-the-art and, in the majority of cases, and outperforms it in most cases in terms of prediction accuracy, generalization, and interpretability.Random Forests (RFs) are powerful ensemble learning algorithms that are widely used in various machine learning tasks. However, they tend to overfit noisy or irrelevant features, which can result in decreased generalization performance. Post-hoc regularization techniques aim to solve this problem by modifying the structure of the learned ensemble after training. We propose a novel post-hoc regularization via tree smoothing for classification tasks to leverage the reliable class distributions closer to the root node whilst reducing the impact of more specific and potentially noisy splits deeper in the tree. Our novel approach allows for a form of pruning that does not alter the general structure of the trees, adjusting the influence of nodes based on their proximity to the root node. We evaluated the performance of our method on various machine learning benchmark data sets and on cancer data from The Cancer Genome Atlas (TCGA). Our approach demonstrates competitive performance compared to the state-of-the-art and, in the majority of cases, and outperforms it in most cases in terms of prediction accuracy, generalization, and interpretability.A