Privacy in Practice: Private COVID-19 Detection in X-Ray Images

Machine learning (ML) can help fight the COVID-19 pandemic by enabling rapid screening of large volumes of chest X-ray images. To perform such data analysis while maintaining patient privacy, we create ML models that satisfy Differential Privacy (DP). Previous works exploring private COVID-19 ML models are in part based on small or skewed datasets, are lacking in their privacy guarantees, and do not investigate practical privacy. In this work, we therefore suggest several improvements to address these open gaps. We account for inherent class imbalances in the data and evaluate the utility-privacy trade-off more extensively and over stricter privacy budgets than in previous work. Our evaluation is supported by empirically estimating practical privacy leakage through actual attacks. Based on theory, the introduced DP should help limit and mitigate information leakage threats posed by black-box Membership Inference Attacks (MIAs). Our practical privacy analysis is the first to test this hypothesis on the COVID-19 detection task. In addition, we also re-examine the evaluation on the MNIST database. Our results indicate that based on the task-dependent threat from MIAs, DP does not always improve practical privacy, which we show on the COVID-19 task. The results further suggest that with increasing DP guarantees, empirical privacy leakage reaches an early plateau and DP therefore appears to have a limited impact on MIA defense. Our findings identify possibilities for better utility-privacy trade-offs, and we thus believe that empirical attack-specific privacy estimation can play a vital role in tuning for practical privacy

Design and performance evaluation of next generation clutch control valve

Pressure reducing valves perform various control tasks in mobile machines. In many cases contamination sensitive environments require pilot-operated valves, because of its more robust performance. On the other hand, dynamic valve behavior can be critically in certain applications. Overcoming the restrictions resulting from stand-alone test rig attempts, suitable simulation principles are nowadays the state of art in valve design. Unsuitable model approaches and missing consideration of the application may result in wrong design decisions. This paper discusses two important modeling issues, in particular the solenoid and spool leakage behavior, in combination with the connected system under control, a pressure-actuated clutch. It is shown, that even for standard proportional valves a critical view on customers´excitation strategy and site of installation decides on success or failure of an already used design variant

Gleiche Sicherheit für alle statt NATO-Vorherrschaft: Beiträge zum 17. Dresdner Friedenssymposium am 21. Februar 2009

Die Projektgruppe „Für eine Globale Friedensordnung“ stellt im Dresdener Friedenssymposium Arbeitsergebnisse vor.:Gerda Krause, Eröffnung. Autorenbeiträge: Peter Strutynsky, Die Globalisierung der NATO oder die Militarisierung des Globus. Erhard Crome, Gleiche Sicherheit für alle - Alternativen zur NATO. Manfred Sauer, NATO – nicht die Sicherheit, die wir meinen. Horst Schneider, Gedanken zum Kolloquiumsthema Gleiche Sicherheit für alle statt NATO-Vorherrschaft. Nachträglich eingereichter Beitrag zum 13. Dresdner Symposium Für eine globale Friedensordnung, Heft 93/2009: Detlef Bald, Das Beispiel vom Primat der Politik – Die Kontrolle der Atomwaffen in der Bonner Republik

Targeting MYC effector functions in pancreatic cancer by inhibiting the ATPase RUVBL1/2

Objective The hallmark oncogene MYC drives the progression of most tumours, but direct inhibition of MYC by a small-molecule drug has not reached clinical testing. MYC is a transcription factor that depends on several binding partners to function. We therefore explored the possibility of targeting MYC via its interactome in pancreatic ductal adenocarcinoma (PDAC). Design To identify the most suitable targets among all MYC binding partners, we constructed a targeted shRNA library and performed screens in cultured PDAC cells and tumours in mice. Results Unexpectedly, many MYC binding partners were found to be important for cultured PDAC cells but dispensable in vivo. However, some were also essential for tumours in their natural environment and, among these, the ATPases RUVBL1 and RUVBL2 ranked first. Degradation of RUVBL1 by the auxin-degron system led to the arrest of cultured PDAC cells but not untransformed cells and to complete tumour regression in mice, which was preceded by immune cell infiltration. Mechanistically, RUVBL1 was required for MYC to establish oncogenic and immunoevasive gene expression identifying the RUVBL1/2 complex as a druggable vulnerability in MYC-driven cancer. Conclusion One implication of our study is that PDAC cell dependencies are strongly influenced by the environment, so genetic screens should be performed in vitro and in vivo. Moreover, the auxin-degron system can be applied in a PDAC model, allowing target validation in living mice. Finally, by revealing the nuclear functions of the RUVBL1/2 complex, our study presents a pharmaceutical strategy to render pancreatic cancers potentially susceptible to immunotherapy

PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1

The establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way it influences cellular differentiation and proliferation. PRMT6 lacks DNA-binding capability but is recruited by transcription factors to regulate gene expression. However, currently only a limited number of transcription factors have been identified, which facilitate recruitment of PRMT6 to key cell cycle related target genes. Here, we show that LEF1 contributes to the recruitment of PRMT6 to the central cell cycle regulator CCND1 (Cyclin D1). We identified LEF1 as an interaction partner of PRMT6. Knockdown of LEF1 or PRMT6 reduces CCND1 expression. This is in line with our observation that knockdown of PRMT6 increases the number of cells in G1 phase of the cell cycle and decreases proliferation. These results improve the understanding of PRMT6 activity in cell cycle regulation. We expect that these insights will foster the rational development and usage of specific PRMT6 inhibitors for cancer therapy.Wilhelm Sander-StiftungDeutsche Forschungsgemeinschaf

Slip of the tongue: implications for evolution and language development

prevailing theory regarding the evolution of language implicates a gestural stage prior to the emergence of speech. In support of a transition of human language from a gestural to a vocal system, articulation of the hands and the tongue are underpinned by overlapping left hemisphere dominant neural regions. Behavioral studies demonstrate that human adults perform sympathetic mouth actions in imitative synchrony with manual actions. Additionally, right-handedness for precision manual actions in children has been corre- lated with the typical development of language, while a lack of hand bias has been associ- ated with psychopathology. It therefore stands to reason that sympathetic mouth actions during fine precision motor action of the hands may be lateralized. We employed a fine-grained behavioral coding paradigm to provide the first investigation of tongue pro- trusions in typically developing 4-year old children. Tongue protrusions were investigated across a range of cognitive tasks that required varying degrees of manual action: precision motor action, gross motor action and no motor actions. The rate of tongue protrusions was influenced by the motor requirements of the task and tongue protrusions were signifi- cantly right-biased for only precision manual motor action (p < .001). From an evolutionary perspective, tongue protrusions can drive new investigations regarding how an early human communication system transitioned from hand to mouth. From a developmental perspective, the present study may serve to reveal patterns of tongue protrusions during the motor development of typically developing children

The unexpected resurgence of Weyl geometry in late 20-th century physics

Weyl's original scale geometry of 1918 ("purely infinitesimal geometry") was withdrawn by its author from physical theorizing in the early 1920s. It had a comeback in the last third of the 20th century in different contexts: scalar tensor theories of gravity, foundations of gravity, foundations of quantum mechanics, elementary particle physics, and cosmology. It seems that Weyl geometry continues to offer an open research potential for the foundations of physics even after the turn to the new millennium.Comment: Completely rewritten conference paper 'Beyond Einstein', Mainz Sep 2008. Preprint ELHC (Epistemology of the LHC) 2017-02, 92 pages, 1 figur

The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis

A network of gene regulatory factors such as transcription factors and microRNAs establish and maintain gene expression patterns during hematopoiesis. In this network, transcription factors regulate each other and are involved in regulatory loops with microRNAs. The microRNA cluster miR-17-92 is located within the MIR17HG gene and encodes six mature microRNAs. It is important for hematopoietic differentiation and plays a central role in malignant disease. However, the transcription factors downstream of miR-17-92 are largely elusive and the transcriptional regulation of miR-17-92 is not fully understood. Here we show that miR-17-92 forms a regulatory loop with the transcription factor TAL1. The miR-17-92 cluster inhibits expression of TAL1 and indirectly leads to decreased stability of the TAL1 transcriptional complex. We found that TAL1 and its heterodimerization partner E47 regulate miR-17-92 transcriptionally. Furthermore, miR-17-92 negatively influences erythroid differentiation, a process that depends on gene activation by the TAL1 complex. Our data give example of how transcription factor activity is fine-tuned during normal hematopoiesis. We postulate that disturbance of the regulatory loop between TAL1 and the miR-17-92 cluster could be an important step in cancer development and progression.Deutsche ForschungsgemeinschaftProjekt DEA

Prolonged Influenza Virus Shedding and Emergence of Antiviral Resistance in Immunocompromised Patients and Ferrets

Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15%) cases with prolonged 2009 pandemic virus replication (longer than 14 days), despite antiviral therapy. In 5 out of these 11 (45%) cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y) 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies