Actually, What Does “Ontology” Mean?

This article is a fictitious, moderated dialogue between an information scientist, a philosopher, and a psychologist. They explore the term “ontology” from the point of view of their own discipline, with the object of learning from each other. The target audience of this article are laypersons with respect to the specific disciplines – but who have a scientific background.The authors work in the fields of computer science, knowledge engineering, electrical engineering, mathematics, neurobiology, philosophy, and psychology.</p

Enhancer hijacking discovery in acute myeloid leukemia by pyjacker identifies MNX1 activation via deletion 7q

Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. Genomic rearrangements can reposition active enhancers near proto-oncogenes, leading to their aberrant expression, however, a comprehensive understanding of these events in AML is still incomplete. To facilitate the discovery of such “enhancer hijacking” events, we developed pyjacker, a computational tool, and applied it to 39 ckAML samples. Pyjacker identified several enhancer hijacking events in AML patient samples, including aberrant expression of motor neuron and pancreas homeobox 1 (MNX1), which can result from del(7)(q22q36) and is associated with hijacking of a CDK6 enhancer. MNX1 activation occurred in 1.4% of AML patients and showed significant co-occurrence with BCOR mutations. Through a xenograft mouse model, we demonstrated that MNX1 is required for leukemia cell fitness. Pyjacker is an easy-to-use, accurate, and broadly applicable tool for identifying consequences of genomic events driving tumorigenesis, especially when germline genomic data is missing

Information processing of chemical stimuli in the trigeminal ganglion

Freie Nervenendigungen sensorischer Neurone des Nervus Trigeminus detektieren physikalische und chemische Stimuli in unterschiedlichen Bereichen des Kopfes. Weiterhin ermöglicht dieser Nerv die Diskriminierung verschiedener volatiler Substanzen, die zugrundeliegenden Mechanismen sind jedoch weitgehend unklar. Die vorliegende Arbeit befasst sich mit verschiedenen Aspekten der trigeminalen Wahrnehmung auf Verhaltensebene, im intakten trigeminalen Ganglion, an kultivierten trigeminalen Neuronen und einzelnen Rezeptoren. Mittels spannungssensitiver Farbstoffe wurden spezifische räumlich-zeitliche Aktivitätsmuster im trigeminalen Ganglion der Ratte charakterisiert, die durch verschiedene volatile Substanzen induziert und wahrscheinlich durch Modulation unterschiedlicher TRP- und K2P-Kanälen in trigeminalen Neuronen zustande kommen. Weiterhin wurde der Einfluss der $[Cl^-]_i$ trigeminaler Neurone auf die trigeminale Wahrnehmung untersucht und die Aktivierung von TRPV1 durch $Ni^2$$^+$ charakterisiert

Adsorption equilibria of α- and δ-tocopherol from supercritical mixtures of carbon dioxide and 2-propanol onto silica by means of perturbation chromatography

For the determination of adsorption isotherms of dissolved components from supercritical fluids, an experimental equipment has been constructed. It consists of a fluid preparation and two chromatographic units with UV detector and pressure expansion. The equipment allows the performance of peak experiments (injecting samples onto an empty column) as well as perturbation experiments (perturbing the equilibrium in a saturated column). Adsorption isotherms of α- and δ-tocopherol on two unmodified silica gels were determined at a temperature of 313.15 K and pressures of 16.1, 20.0, and 26.1 MPa, respectively. Fluid phase was CO2 with 2-propanol (weight fraction 0.05) as modifier. Parameters of a cubic Hill isotherm were fitted to the data. Ideal adsorbed solution theory (IAST) was applied for prediction of mixture adsorption. Applicability of IAST was tested with perturbation chromatographic experiments using different mixtures. All isotherms show anti-Langmuir behaviour (concave shaped isotherms). These results agree with literature data. Competitive adsorption was successfully predicted by means of the IAS theory

Separation of ibuprofen enantiomers by supercritical fluid simulated moving bed chromatography

The continuous separation of R(-)-ibuprofen and S(+)-ibuprofen by supercritical fluid simulated moving bed chromatography has been developed. First, experiments were performed at a low concentration level. Therefore, a starting set of operating parameters was calculated using the "triangle theory," which has been developed in the frame of equilibrium theory. Subsequently, the feed concentration was increased. A dynamic simulation program, based on a plug flow model with axial dispersion and linear mass transfer resistance, was used to predict the effect of operating variables on the process performance. Adsorption isotherms were determined with the elution by a characteristic point method. The experimental results were compared both with the model predictions based on the triangle theory and with the results of simulations

Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report

Abstract Background Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy. Case presentation A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 μg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found. For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered. Conclusions Under a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity. </jats:sec

Mechanical plus oral bowel preparation with paromomycin and metronidazole reduces infectious complications in elective colorectal surgery: a matched case-control study

Abstract Purpose Infectious complications are as high as 30% in elective colorectal surgery. In recent years, several studies have discussed the topic of preoperative bowel decontamination prior to colorectal surgery in order to reduce postoperative infectious complications and have found significant effects of oral antibiotic administration with a large variety of drugs used. No study has evaluated the combination of oral paromomycin and metronidazole in this context. Methods We performed a prospective single-center study with a matched-pair retrospective cohort to evaluate postoperative infectious complications (superficial site infections, organ space abscess, anastomotic leakage) in elective colorectal surgery. Patients A total of 120 patients were available for study inclusion; 101 gave informed consent and were included. A total of 92 patients were matched and subsequently analyzed. We could show a reduction in overall infectious complications in the intervention group (15.2% vs 30.8%, p = 0.018; odds ratio 0.333, 95% CI 0.142–0.784) as well as a reduction in superficial surgical site infections (8.7 vs 19.6%, p = 0.041, OR 0.333, 95% CI 0.121–0.917). The frequency of the other infectious complications such as intraabdominal abscesses and anastomotic leakage showed a tendency towards decreased frequencies in the intervention group (OR 0.714, 95% CI 0.235–2.169 and OR 0.571; 95% CI 0.167–1.952, respectively). Finally, the oral antibiotic administration led to an almost significantly reduced length of stay (12.24 days vs 15.25 days; p = 0.057). Conclusions Oral paromomycin and metronidazole with intravenous ertapenem effectively reduce infectious complications in elective colorectal surgery. Trial registration The study was registered at Clinicaltrials.gov (NCT03759886) December 17, 2018 </jats:sec

Mechanical plus oral bowel preparation with paromomycin and metronidazole reduces infectious complications in elective colorectal surgery: a matched case-control study

Purpose!#!Infectious complications are as high as 30% in elective colorectal surgery. In recent years, several studies have discussed the topic of preoperative bowel decontamination prior to colorectal surgery in order to reduce postoperative infectious complications and have found significant effects of oral antibiotic administration with a large variety of drugs used. No study has evaluated the combination of oral paromomycin and metronidazole in this context.!##!Methods!#!We performed a prospective single-center study with a matched-pair retrospective cohort to evaluate postoperative infectious complications (superficial site infections, organ space abscess, anastomotic leakage) in elective colorectal surgery.!##!Patients!#!A total of 120 patients were available for study inclusion; 101 gave informed consent and were included. A total of 92 patients were matched and subsequently analyzed. We could show a reduction in overall infectious complications in the intervention group (15.2% vs 30.8%, p = 0.018; odds ratio 0.333, 95% CI 0.142-0.784) as well as a reduction in superficial surgical site infections (8.7 vs 19.6%, p = 0.041, OR 0.333, 95% CI 0.121-0.917). The frequency of the other infectious complications such as intraabdominal abscesses and anastomotic leakage showed a tendency towards decreased frequencies in the intervention group (OR 0.714, 95% CI 0.235-2.169 and OR 0.571; 95% CI 0.167-1.952, respectively). Finally, the oral antibiotic administration led to an almost significantly reduced length of stay (12.24 days vs 15.25 days; p = 0.057).!##!Conclusions!#!Oral paromomycin and metronidazole with intravenous ertapenem effectively reduce infectious complications in elective colorectal surgery.!##!Trial registration!#!The study was registered at Clinicaltrials.gov (NCT03759886) December 17, 2018

Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants), environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants). In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia