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Co-design of a trustworthy AI system in healthcare: deep learning based skin lesion classifier
(2021)
This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approach rather than a static ethical checklist and required a multidisciplinary team of experts working with the AI designers and their managers. Ethical, legal, and technical issues potentially arising from the future use of the AI system were investigated. This paper is a first report on co-designing in the early design phase. Our results can also serve as guidance for other early-phase AI-similar tool developments.
Human lymph nodes play a central part of immune defense against infection agents and tumor cells. Lymphoid follicles are compartments of the lymph node which are spherical, mainly filled with B cells. B cells are cellular components of the adaptive immune systems. In the course of a specific immune response, lymphoid follicles pass different morphological differentiation stages. The morphology and the spatial distribution of lymphoid follicles can be sometimes associated to a particular causative agent and development stage of a disease. We report our new approach for the automatic detection of follicular regions in histological whole slide images of tissue sections immuno-stained with actin. The method is divided in two phases: (1) shock filter-based detection of transition points and (2) segmentation of follicular regions. Follicular regions in 10 whole slide images were manually annotated by visual inspection, and sample surveys were conducted by an expert pathologist. The results of our method were validated by comparing with the manual annotation. On average, we could achieve a Zijbendos similarity index of 0.71, with a standard deviation of 0.07.
Network graphs have become a popular tool to represent complex systems composed of many interacting subunits; especially in neuroscience, network graphs are increasingly used to represent and analyze functional interactions between multiple neural sources. Interactions are often reconstructed using pairwise bivariate analyses, overlooking the multivariate nature of interactions: it is neglected that investigating the effect of one source on a target necessitates to take all other sources as potential nuisance variables into account; also combinations of sources may act jointly on a given target. Bivariate analyses produce networks that may contain spurious interactions, which reduce the interpretability of the network and its graph metrics. A truly multivariate reconstruction, however, is computationally intractable because of the combinatorial explosion in the number of potential interactions. Thus, we have to resort to approximative methods to handle the intractability of multivariate interaction reconstruction, and thereby enable the use of networks in neuroscience. Here, we suggest such an approximative approach in the form of an algorithm that extends fast bivariate interaction reconstruction by identifying potentially spurious interactions post-hoc: the algorithm uses interaction delays reconstructed for directed bivariate interactions to tag potentially spurious edges on the basis of their timing signatures in the context of the surrounding network. Such tagged interactions may then be pruned, which produces a statistically conservative network approximation that is guaranteed to contain non-spurious interactions only. We describe the algorithm and present a reference implementation in MATLAB to test the algorithm’s performance on simulated networks as well as networks derived from magnetoencephalographic data. We discuss the algorithm in relation to other approximative multivariate methods and highlight suitable application scenarios. Our approach is a tractable and data-efficient way of reconstructing approximative networks of multivariate interactions. It is preferable if available data are limited or if fully multivariate approaches are computationally infeasible.
The amyloid precursor protein (APP) was discovered in the 1980s as the precursor protein of the amyloid A4 peptide. The amyloid A4 peptide, also known as A-beta (Aβ), is the main constituent of senile plaques implicated in Alzheimer’s disease (AD). In association with the amyloid deposits, increasing impairments in learning and memory as well as the degeneration of neurons especially in the hippocampus formation are hallmarks of the pathogenesis of AD. Within the last decades much effort has been expended into understanding the pathogenesis of AD. However, little is known about the physiological role of APP within the central nervous system (CNS). Allocating APP to the proteome of the highly dynamic presynaptic active zone (PAZ) identified APP as a novel player within this neuronal communication and signaling network. The analysis of the hippocampal PAZ proteome derived from APP-mutant mice demonstrates that APP is tightly embedded in the underlying protein network. Strikingly, APP deletion accounts for major dysregulation within the PAZ proteome network. Ca2+-homeostasis, neurotransmitter release and mitochondrial function are affected and resemble the outcome during the pathogenesis of AD. The observed changes in protein abundance that occur in the absence of APP as well as in AD suggest that APP is a structural and functional regulator within the hippocampal PAZ proteome. Within this review article, we intend to introduce APP as an important player within the hippocampal PAZ proteome and to outline the impact of APP deletion on individual PAZ proteome subcommunities.
Human functional brain connectivity can be temporally decomposed into states of high and low cofluctuation, defined as coactivation of brain regions over time. Rare states of particularly high cofluctuation have been shown to reflect fundamentals of intrinsic functional network architecture and to be highly subject-specific. However, it is unclear whether such network-defining states also contribute to individual variations in cognitive abilities – which strongly rely on the interactions among distributed brain regions. By introducing CMEP, a new eigenvector-based prediction framework, we show that as few as 16 temporally separated time frames (< 1.5% of 10min resting-state fMRI) can significantly predict individual differences in intelligence (N = 263, p < .001). Against previous expectations, individual’s network-defining time frames of particularly high cofluctuation do not predict intelligence. Multiple functional brain networks contribute to the prediction, and all results replicate in an independent sample (N = 831). Our results suggest that although fundamentals of person-specific functional connectomes can be derived from few time frames of highest connectivity, temporally distributed information is necessary to extract information about cognitive abilities. This information is not restricted to specific connectivity states, like network-defining high-cofluctuation states, but rather reflected across the entire length of the brain connectivity time series.
Event-related potentials (ERPs) are widely used in basic neuroscience and in clinical diagnostic procedures. In contrast, neurophysiological insights from ERPs have been limited, as several different mechanisms lead to ERPs. Apart from stereotypically repeated responses (additive evoked responses), these mechanisms are asymmetric amplitude modulations and phase-resetting of ongoing oscillatory activity. Therefore, a method is needed that differentiates between these mechanisms and moreover quantifies the stability of a response. We propose a constrained subspace independent component analysis that exploits the multivariate information present in the all-to-all relationship of recordings over trials. Our method identifies additive evoked activity and quantifies its stability over trials. We evaluate identification performance for biologically plausible simulation data and two neurophysiological test cases: Local field potential (LFP) recordings from a visuo-motor-integration task in the awake behaving macaque and magnetoencephalography (MEG) recordings of steady-state visual evoked fields (SSVEFs). In the LFPs we find additive evoked response contributions in visual areas V2/4 but not in primary motor cortex A4, although visually triggered ERPs were also observed in area A4. MEG-SSVEFs were mainly created by additive evoked response contributions. Our results demonstrate that the identification of additive evoked response contributions is possible both in invasive and in non-invasive electrophysiological recordings.
Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism’s preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.
Correction to: Scientifc Reports https://doi.org/10.1038/s41598-019-43857-5, published online 17 May 2019. In the original version of this Article, Jan-Hendrik Trösemeier was incorrectly affiliated with ‘Division of Allergology, Paul Ehrlich Institut, Langen, Germany’. Te correct afliations are listed below...
Background: Although mortality after cardiac surgery has significantly decreased in the last decade, patients still experience clinically relevant postoperative complications. Among others, atrial fibrillation (AF) is a common consequence of cardiac surgery, which is associated with prolonged hospitalization and increased mortality.
Methods: We retrospectively analyzed data from patients who underwent coronary artery bypass grafting, valve surgery or a combination of both at the University Hospital Muenster between April 2014 and July 2015. We evaluated the incidence of new onset and intermittent/permanent AF (patients with pre- and postoperative AF). Furthermore, we investigated the impact of postoperative AF on clinical outcomes and evaluated potential risk factors.
Results: In total, 999 patients were included in the analysis. New onset AF occurred in 24.9% of the patients and the incidence of intermittent/permanent AF was 59.5%. Both types of postoperative AF were associated with prolonged ICU length of stay (median increase approx. 2 days) and duration of mechanical ventilation (median increase 1 h). Additionally, new onset AF patients had a higher rate of dialysis and hospital mortality and more positive fluid balance on the day of surgery and postoperative days 1 and 2. In a multiple logistic regression model, advanced age (odds ratio (OR) = 1.448 per decade increase, p < 0.0001), a combination of CABG and valve surgery (OR = 1.711, p = 0.047), higher C-reactive protein (OR = 1.06 per unit increase, p < 0.0001) and creatinine plasma concentration (OR = 1.287 per unit increase, p = 0.032) significantly predicted new onset AF. Higher Horowitz index values were associated with a reduced risk (OR = 0.996 per unit increase, p = 0.012). In a separate model, higher plasma creatinine concentration (OR = 2.125 per unit increase, p = 0.022) was a significant risk factor for intermittent/permanent AF whereas higher plasma phosphate concentration (OR = 0.522 per unit increase, p = 0.003) indicated reduced occurrence of this arrhythmia.
Conclusions: New onset and intermittent/permanent AF are associated with adverse clinical outcomes of elective cardiac surgery patients. Different risk factors implicated in postoperative AF suggest different mechanisms might be involved in its pathogenesis. Customized clinical management protocols seem to be warranted for a higher success rate of prevention and treatment of postoperative AF.
Die Erwartungen von Studieninteressierten weichen häufig beträchtlich von den tatsächlichen Studieninhalten und Anforderungen ab. Ein Grund dafür ist, dass viele sich nicht genügend Klarheit verschaffen, welche eigenen Stärken und Schwächen für den Erfolg in Studium und Beruf »tatsächlich« relevant sind. So könnte zum Beispiel ein Abiturient mit guten Noten in Mathematik und Physik und mäßigen Zensuren in Deutsch und Englisch noch schlussfolgern, dass ihm »das Naturwissenschaftliche mehr liegt«. Ob das naturwissenschaftliche Verständnis für ein erfolgreiches Studium der Informatik jedoch gut genug ausgeprägt ist, lässt sich nicht so leicht erschließen. Noch schwieriger ist es für Studieninteressierte einzuschätzen, wie ihre »Soft Skills« ausgeprägt sind – also die Persönlichkeitsmerkmale, die in der Schule nicht systematisch beurteilt werden, jedoch hochgradig aussagekräftig für langfristigen Erfolg in Studium und Beruf sind. Ein Wechsel des Studienfaches zu Beginn des Studiums führt häufig zu einer Verlängerung der Studiendauer. Auch wenn eine derartige »Orientierungsphase« oftmals als normal und wichtig eingeschätzt wird, zeigt die praktische Erfahrung, dass Studierende mit kurzer Studiendauer jenen, die länger studiert haben, bei der Stellenvergabe tendenziell vorgezogen werden. Eine längere Studiendauer wird von Arbeitgebern häufig als Zeichen mangelnder Zielstrebigkeit oder fehlender Berufsmotivation interpretiert und kann sich so Chancen mindernd für Berufseinsteiger auswirken. Ebenso ist es im Interesse der Universitäten, die Zahl der Studienfachwechsel und -abbrüche so gering wie möglich zu halten – nicht zuletzt aus wirtschaftlichen Gründen. Deshalb bietet die Universität Frankfurt Studieninteressierten – zunächst in den Fächern Informatik und Psychologie – mit dem Self-Assessment konkrete Entscheidungshilfen an. Der verfolgte Ansatz zielt darauf ab, Abiturientinnen und Abiturienten möglichst frühzeitig und mit vertretbarem Aufwand die Möglichkeit zu bieten, selbst zu überprüfen, inwieweit ihre Erwartungen an einen Studiengang mit den tatsächlichen Inhalten und Anforderungen übereinstimmen. Das Konzept zur Erstellung eines Self-Assessments, das hier beispielhaft für den Studiengang Informatik vorgestellt wird, entstand nicht umsonst in enger Kooperation mit dem Institut für Psychologie (Prof. Dr. Helfried Moosbrugger, Dr. Siegbert Reiß, Ewa Jonkisz). Denn neben der fachlichen Qualifikation entscheiden über den Studienerfolg auch persönliche Eigenschaften wie Leistungsbereitschaft und Hartnäckigkeit. Die Auswertung des anonym durchgeführten Self-Assessments deckt außerdem Wissenslücken bei den Studieninteressierten auf, so dass eine gezielte Vorbereitung auf das Studium möglich wird. Zum Beispiel bietet der Fachbereich Mathematik und Informatik gezielte Vorbereitungskurse für Studienanfänger an, und zwar in Programmierung und Mathematik. Auch werden in den Semesterferien Repetitorien und Vorbereitungskurse angeboten – alles aus Studienbeiträgen finanziert. Auf diese Weise kann es zu einem homogeneren Kenntnisstand speziell bei den Studierenden im ersten Semester kommen. Ziel ist es, dadurch auch den »Erstsemesterschock « zu mildern. Das Online-Beratungsangebot trägt damit zu einer direkten Verbesserung der Lern- und Lehrsituation bei.
We present the FPGA implementation of an algorithm [4] that computes implications between signal values in a boolean network. The research was performed as a masterrsquos thesis [5] at the University of Frankfurt. The recursive algorithm is rather complex for a hardware realization and therefore the FPGA implementation is an interesting example for the potential of reconfigurable computing beyond systolic algorithms. A circuit generator was written that transforms a boolean network into a network of small processing elements and a global control logic which together implement the algorithm. The resulting circuit performs the computation two orders of magnitudes faster than a software implementation run by a conventional workstation.
Channel routing is an NP-complete problem. Therefore, it is likely that there is no efficient algorithm solving this problem exactly.In this paper, we show that channel routing is a fixed-parameter tractable problem and that we can find a solution in linear time for a fixed channel width.We implemented our approach for the restricted layer model. The algorithm finds an optimal route for channels with up to 13 tracks within minutes or up to 11 tracks within seconds.Such narrow channels occur for example as a leaf problem of hierarchical routers or within standard cell generators.
Assessing enhanced knowledge discovery systems (eKDSs) constitutes an intricate issue that is understood merely to a certain extent by now. Based upon an analysis of why it is difficult to formally evaluate eKDSs, it is argued for a change of perspective: eKDSs should be understood as intelligent tools for qualitative analysis that support, rather than substitute, the user in the exploration of the data; a qualitative gap will be identified as the main reason why the evaluation of enhanced knowledge discovery systems is difficult. In order to deal with this problem, the construction of a best practice model for eKDSs is advocated. Based on a brief recapitulation of similar work on spoken language dialogue systems, first steps towards achieving this goal are performed, and directions of future research are outlined.
Syntactic coindexing restrictions are by now known to be of central importance to practical anaphor resolution approaches. Since, in particular due to structural ambiguity, the assumption of the availability of a unique syntactic reading proves to be unrealistic, robust anaphor resolution relies on techniques to overcome this deficiency.
This paper describes the ROSANA approach, which generalizes the verification of coindexing restrictions in order to make it applicable to the deficient syntactic descriptions that are provided by a robust state-of-the-art parser. By a formal evaluation on two corpora that differ with respect to text genre and domain, it is shown that ROSANA achieves high-quality robust coreference resolution. Moreover, by an in-depth analysis, it is proven that the robust implementation of syntactic disjoint reference is nearly optimal. The study reveals that, compared with approaches that rely on shallow preprocessing, the largely nonheuristic disjoint reference algorithmization opens up the possibility/or a slight improvement. Furthermore, it is shown that more significant gains are to be expected elsewhere, particularly from a text-genre-specific choice of preference strategies.
The performance study of the ROSANA system crucially rests on an enhanced evaluation methodology for coreference resolution systems, the development of which constitutes the second major contribution o/the paper. As a supplement to the model-theoretic scoring scheme that was developed for the Message Understanding Conference (MUC) evaluations, additional evaluation measures are defined that, on one hand, support the developer of anaphor resolution systems, and, on the other hand, shed light on application aspects of pronoun interpretation.
We present a theoretical analysis of structural FSM traversal, which is the basis for the sequential equivalence checking algorithm Record & Play presented earlier. We compare the convergence behaviour of exact and approximative structural FSM traversal with that of standard BDD-based FSM traversal. We show that for most circuits encountered in practice exact structural FSM traversal reaches the fixed point as fast as symbolic FSM traversal, while approximation can significantly reduce in the number of iterations needed. Our experiments confirm these results.
One of the most severe short-comings of currently available equivalence checkers is their inability to verify integer multipliers. In this paper, we present a bit level reverse-engineering technique that can be integrated into standard equivalence checking flows. We propose a Boolean mapping algorithm that extracts a network of half adders from the gate netlist of an addition circuit. Once the arithmetic bit level representation of the circuit is obtained, equivalence checking can be performed using simple arithmetic operations. Experimental results show the promise of our approach.
50 years of amino acid hydrophobicity scales : revisiting the capacity for peptide classification
(2016)
Background: Physicochemical properties are frequently analyzed to characterize protein-sequences of known and unknown function. Especially the hydrophobicity of amino acids is often used for structural prediction or for the detection of membrane associated or embedded β-sheets and α-helices. For this purpose many scales classifying amino acids according to their physicochemical properties have been defined over the past decades. In parallel, several hydrophobicity parameters have been defined for calculation of peptide properties. We analyzed the performance of separating sequence pools using 98 hydrophobicity scales and five different hydrophobicity parameters, namely the overall hydrophobicity, the hydrophobic moment for detection of the α-helical and β-sheet membrane segments, the alternating hydrophobicity and the exact ß-strand score.
Results: Most of the scales are capable of discriminating between transmembrane α-helices and transmembrane β-sheets, but assignment of peptides to pools of soluble peptides of different secondary structures is not achieved at the same quality. The separation capacity as measure of the discrimination between different structural elements is best by using the five different hydrophobicity parameters, but addition of the alternating hydrophobicity does not provide a large benefit. An in silico evolutionary approach shows that scales have limitation in separation capacity with a maximal threshold of 0.6 in general. We observed that scales derived from the evolutionary approach performed best in separating the different peptide pools when values for arginine and tyrosine were largely distinct from the value of glutamate. Finally, the separation of secondary structure pools via hydrophobicity can be supported by specific detectable patterns of four amino acids.
Conclusion: It could be assumed that the quality of separation capacity of a certain scale depends on the spacing of the hydrophobicity value of certain amino acids. Irrespective of the wealth of hydrophobicity scales a scale separating all different kinds of secondary structures or between soluble and transmembrane peptides does not exist reflecting that properties other than hydrophobicity affect secondary structure formation as well. Nevertheless, application of hydrophobicity scales allows distinguishing between peptides with transmembrane α-helices and β-sheets. Furthermore, the overall separation capacity score of 0.6 using different hydrophobicity parameters could be assisted by pattern search on the protein sequence level for specific peptides with a length of four amino acids.
Risk evaluations for agricultural chemicals are necessary to preserve healthy populations of honey bee colonies. Field studies on whole colonies are limited in behavioural research, while results from lab studies allow only restricted conclusions on whole colony impacts. Methods for automated long-term investigations of behaviours within comb cells, such as brood care, were hitherto missing. In the present study, we demonstrate an innovative video method that enables within-cell analysis in honey bee (Apis mellifera) observation hives to detect chronic sublethal neonicotinoid effects of clothianidin (1 and 10 ppb) and thiacloprid (200 ppb) on worker behaviour and development. In May and June, colonies which were fed 10 ppb clothianidin and 200 ppb thiacloprid in syrup over three weeks showed reduced feeding visits and duration throughout various larval development days (LDDs). On LDD 6 (capping day) total feeding duration did not differ between treatments. Behavioural adaptation was exhibited by nurses in the treatment groups in response to retarded larval development by increasing the overall feeding timespan. Using our machine learning algorithm, we demonstrate a novel method for detecting behaviours in an intact hive that can be applied in a versatile manner to conduct impact analyses of chemicals, pests and other stressors.
Poster presentation: The analysis of neuronal processes distributed across multiple cortical areas aims at the identification of interactions between signals recorded at different sites. Such interactions can be described by measuring the stability of phase angles in the case of oscillatory signals or other forms of signal dependencies for less regular signals. Before, however, any form of interaction can be analyzed at a given time and frequency, it is necessary to assess whether all potentially contributing signals are present. We have developed a new statistical procedure for the detection of coincident power in multiple simultaneously recorded analog signals, allowing the classification of events as 'non-accidental co-activation'. This method can effectively operate on single trials, each lasting only for a few seconds. Signals need to be transformed into time-frequency space, e.g. by applying a short-time Fourier transformation using a Gaussian window. The discrete wavelet transform (DWT) is used in order to weight the resulting power patterns according to their frequency. Subsequently, the weighted power patterns are binarized via applying a threshold. At this final stage, significant power coincidence is determined across all subgroups of channel combinations for individual frequencies by selecting the maximum ratio between observed and expected duration of co-activation as test statistic. The null hypothesis that the activity in each channel is independent from the activity in every other channel is simulated by independent, random rotation of the respective activity patterns. We applied this procedure to single trials of multiple simultaneously sampled local field potentials (LFPs) obtained from occipital, parietal, central and precentral areas of three macaque monkeys. Since their task was to use visual cues to perform a precise arm movement, co-activation of numerous cortical sites was expected. In a data set with 17 channels analyzed, up to 13 sites expressed simultaneous power in the range between 5 and 240 Hz. On average, more than 50% of active channels participated at least once in a significant power co-activation pattern (PCP). Because the significance of such PCPs can be evaluated at the level of single trials, we are confident that this procedure is useful to study single trial variability with sufficient accuracy that much of the behavioral variability can be explained by the dynamics of the underlying distributed neuronal processes.