Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases

Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type– and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants—including variants that do not reach genome-wide significance—often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissue

Enhanced protein immobilization on polymers - a plasma surface activation study

Over the last years, polymers have gained great attention as substrate material, because of the possibility to produce low-cost sensors in a high-throughput manner or for rapid prototyping and the wide variety of polymeric materials available with different features (like transparency, flexibility, stretchability, etc.). For almost all biosensing applications, the interaction between biomolecules (for example, antibodies, proteins or enzymes) and the employed substrate surface is highly important. In order to realize an effective biomolecule immobilization on polymers, different surface activation techniques, including chemical and physical methods, exist. Among them, plasma treatment offers an easy, fast and effective activation of the surfaces by micro/nanotexturing and generating functional groups (including carboxylic acids, amines, esters, aldehydes or hydroxyl groups). Hence, here we present a systematic and comprehensive plasma activation study of various polymeric surfaces by optimizing different parameters, including power, time, substrate temperature and gas composition. Thereby, the highest immobilization efficiency along with a homogenous biomolecule distribution is achieved with a 5-min plasma treatment under a gas composition of 50% oxygen and nitrogen, at a power of 1000 W and a substrate temperature of 80 C. These results are also confirmed by different surface characterization methods, including SEM, XPS and contact angle measurements

Primary melanoma of the prostate: case report and review of the literature

Background: Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease. Case presentation: Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin’s disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated. Conclusion: Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed

The Quantity Theory of Money is Valid. The New Keynesians are Wrong!

We test the quantity theory of money (QTM) using a novel approach and a large new sample. We do not follow the usual approach of first differentiating the logarithm of the Cambridge equation to obtain an equation relating the growth rate of real GDP, the growth rate of money and inflation. These variables must then again be ‘integrated’ by averaging in order to obtain stable relationships. Instead we suggest a much simpler procedure for testing directly the stability of the coefficient of the Cambridge equation. For 125 countries and post-war data we find the coefficient to be surprisingly stable. We do not select for high inflation episodes as was done in most empirical studies; inflation rates do not even appear in our data set. Much work supporting the QTM has been done by economic historians and at the University of Chicago by Milton Friedman and his associates. The QTM was a foundation stone of the monetarist revolution. Subsequently belief in it waned. The currently dominant New Keynesian School, implicitly or explicitly denies the validity of the QTM. We survey this history and argue that the QTM is valid and New Keynesians are wrong

ac-Field-Controlled Anderson Localization in Disordered Semiconductor Superlattices

An ac field, tuned exactly to resonance with the Stark ladder in an ideal tight binding lattice under strong dc bias, counteracts Wannier-Stark localization and leads to the emergence of extended Floquet states. If there is random disorder, these states localize. The localization lengths depend non-monotonically on the ac field amplitude and become essentially zero at certain parameters. This effect is of possible relevance for characterizing the quality of superlattice samples, and for performing experiments on Anderson localization in systems with well-defined disorder.Comment: 10 pages, Latex; figures available on request from [email protected]

Galactic-Scale Outflow and Supersonic Ram-Pressure Stripping in the Virgo Cluster Galaxy NGC 4388

The Hawaii Imaging Fabry-Perot Interferometer (HIFI) on the University of Hawaii 2.2m telescope was used to map the Halpha and [O III] 5007 A emission-line profiles across the entire disk of the edge-on Sb galaxy NGC 4388. We confirm a rich complex of highly ionized gas that extends ~4 kpc above the disk of this galaxy. Low-ionization gas associated with star formation is also present in the disk. Evidence for bar streaming is detected in the disk component and is discussed in a companion paper (Veilleux, Bland-Hawthorn, & Cecil 1999; hereafter VBC). Non-rotational blueshifted velocities of 50 - 250 km/s are measured in the extraplanar gas north-east of the nucleus. The brighter features in this complex tend to have more blueshifted velocities. A redshifted cloud is also detected 2 kpc south-west of the nucleus. The velocity field of the extraplanar gas of NGC 4388 appears to be unaffected by the inferred supersonic (Mach number M ~ 3) motion of this galaxy through the ICM of the Virgo cluster. We argue that this is because the galaxy and the high-|z| gas lie behind a Mach cone with opening angle ~ 80 degrees. The shocked ICM that flows near the galaxy has a velocity of ~ 500 km/s and exerts insufficient ram pressure on the extraplanar gas to perturb its kinematics. We consider several explanations of the velocity field of the extraplanar gas. Velocities, especially blueshifted velocities on the N side of the galaxy, are best explained as a bipolar outflow which is tilted by > 12 degrees from the normal to the disk. The observed offset between the extraplanar gas and the radio structure may be due to buoyancy or refractive bending by density gradients in the halo gas. Velocity substructure in the outflowing gas also suggests an interaction with ambient halo gas.Comment: 29 pages including 5 figures, Latex, requires aaspp4.sty, to appear in ApJ, 520 (July 20, 1999 issue

A viable and sustainable European path into space – for cargo and astronauts

A think tank of DLR space-research institutes and ArianeGroup reflected on the launcher perspectives, broadening the mission capabilities for European access to space including human mission towards LEO, supporting potential future commercial markets. The Ariane 6 launcher is to be evolved with perspective of enhanced versatility and reduced costs. Also, a new generation of modern, high-performance launchers is to be prepared that is capable of serving all major missions relevant to Europe. The paper summarizes major results of preliminary technical design studies performed in Germany, both for a future Ariane 6 evolution including astronaut transport to and from LEO and for the next generation of partially reusable concepts. Return of the RLV is pondering options of powered descent and vertical landing and smart winged return technologies with horizontal landing close to the launch site. The main propulsion system is considering LOX-LH2 in different cycle architectures as well as LOX-LCH4 of the ongoing PROMETHEUS development program. For the studied concepts, the overall shape and aerodynamic configuration, the propulsion system, the architecture and lay-out of the stages are described and different technical solutions of RLV concepts are compared

The 10m AEI prototype facility A brief overview

The AEI 10 m prototype interferometer facility is currently being constructed at the Albert Einstein Institute in Hannover, Germany. It aims to perform experiments for future gravitational wave detectors using advanced techniques. Seismically isolated benches are planned to be interferometrically interconnected and stabilized, forming a low-noise testbed inside a 100 m^3 ultra-high vacuum system. A well-stabilized high power laser will perform differential position readout of 100 g test masses in a 10 m suspended arm-cavity enhanced Michelson interferometer at the crossover of measurement (shot) noise and backaction (quantum radiation pressure) noise, the so-called Standard Quantum Limit (SQL). Such a sensitivity enables experiments in the highly topical field of macroscopic quantum mechanics. In this article we introduce the experimental facility and describe the methods employed, technical details of subsystems will be covered in future papers

Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?

© 2020, The Author(s). Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into ‘knowing-that’ and ‘knowing-how.’ We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining ‘when is expertise in research integration and implementation required?,’ we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering ‘where can expertise in research integration and implementation currently be found?,’ we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring ‘what is required to strengthen expertise in research integration and implementation?,’ we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained

Conditional embryonic lethality to improve the sterile insect technique in Ceratitis capitata (Diptera: Tephritidae)

<p>Abstract</p> <p>Background</p> <p>The sterile insect technique (SIT) is an environment-friendly method used in area-wide pest management of the Mediterranean fruit fly <it>Ceratitis capitata </it>(Wiedemann; Diptera: Tephritidae). Ionizing radiation used to generate reproductive sterility in the mass-reared populations before release leads to reduction of competitiveness.</p> <p>Results</p> <p>Here, we present a first alternative reproductive sterility system for medfly based on transgenic embryonic lethality. This system is dependent on newly isolated medfly promoter/enhancer elements of cellularization-specifically-expressed genes. These elements act differently in expression strength and their ability to drive lethal effector gene activation. Moreover, position effects strongly influence the efficiency of the system. Out of 60 combinations of driver and effector construct integrations, several lines resulted in larval and pupal lethality with one line showing complete embryonic lethality. This line was highly competitive to wildtype medfly in laboratory and field cage tests.</p> <p>Conclusion</p> <p>The high competitiveness of the transgenic lines and the achieved 100% embryonic lethality causing reproductive sterility without the need of irradiation can improve the efficacy of operational medfly SIT programs.</p