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Práce se zabývá návrhem rozšíření stávající manipulační plochy pro vnik nových deponií těženého materiálu v daném lomu. Navržení pozemních komunikací a zatrubněním údolí potoka., The work deals with the design of the extension of the existing handling area for the entry of new deposits of mined material in the given quarry. Design of roads and piping of stream valleys., Dopravní fakulta Jana Pernera, Uchazeč stručně seznámil komisi se svou diplomovou prací. Po prezentaci hlavních výsledků a závěrů diplomové práce zodpověděl dotazy vedoucího a připomínky oponenta diplomové práce (uvedeny v posudcích práce). V diskusi o diplomové práci stručně zodpověděl všechny dotazy členů komise., Dokončená práce s úspěšnou obhajobou

We study the exclusive diffractive $c \bar c$ photoproduction in ultraperipheral $pA$ collisions. The formalism makes use of off-diagonal generalizations of the unintegrated gluon distribution, the so-called generalized transverse momentum dependent distributions (GTMDs). We present two different formulations. The first one is based directly on gluon GTMD parametrizations in momentum space. Another option is the calculation of the GTMD as a Fourier transform of the dipole-nucleon scattering amplitude $N(Y,\vec{r}_{\perp},\vec{b}_{\perp})$. The latter approach requires some extra regularization discussed in the paper. Different dipole amplitudes from the literature are used. Compared to previous calculations in the literature, we integrate over the full phase space and therefore cross sections for realistic conditions are obtained. We present distributions in rapidity of $c$ or $\bar c$, transverse momentum of the $c \bar c$ pair, four-momentum transfer squared as well as the azimuthal correlation between a sum and a difference of the $c$ and $\bar c$ transverse momenta. The azimuthal correlations are partially due to the so-called elliptic gluon Wigner distribution. Different models lead to different modulations in the azimuthal angle. The modulations are generally smaller than 5%. They depend on the range of transverse momentum selected for the calculation., Comment: 19 pages, 11 figures, 1 table

We report on laser cooling of a large fraction of positronium (Ps) in free-flight by strongly saturating the $1^3S$-$2^3P$ transition with a broadband, long-pulsed 243 nm alexandrite laser. The ground state Ps cloud is produced in a magnetic and electric field-free environment. We observe two different laser-induced effects. The first effect is an increase in the number of atoms in the ground state after the time Ps has spent in the long-lived $3^3P$ states. The second effect is the one-dimensional Doppler cooling of Ps, reducing the cloud's temperature from 380(20) K to 170(20) K. We demonstrate a 58(9) % increase in the coldest fraction of the Ps ensemble., Comment: 6 pages, 5 figures

Bio-telemetry from small tags attached to animals is one of the principal methods for studying the ecology and behaviour of wildlife. The field has constantly evolved over the last 80 years as technological improvement enabled a diversity of sensors to be integrated into the tags (e.g., GPS, accelerometers, etc.). However, retrieving data from tags on free-ranging animals remains a challenge since satellite and GSM networks are relatively expensive and or power hungry. Recently a new class of low-power communication networks have been developed and deployed worldwide to connect the internet of things (IoT). Here, we evaluated one of these, the Sigfox IoT network, for the potential as a real-time multi-sensor data retrieval and tag commanding system for studying fauna across a diversity of species and ecosystems. We tracked 312 individuals across 30 species (from 25 g bats to 3 t elephants) with seven different device concepts, resulting in more than 177,742 successful transmissions. We found a maximum line of sight communication distance of 280 km (on a flying cape vulture [Gyps coprotheres]), which sets a new documented record for animal-borne digital data transmission using terrestrial infrastructure. The average transmission success rate amounted to 68.3% (SD 22.1) on flying species and 54.1% (SD 27.4) on terrestrial species. In addition to GPS data, we also collected and transmitted data products from accelerometers, barometers, and thermometers. Further, we assessed the performance of Sigfox Atlas Native, a low-power method for positional estimates based on radio signal strengths and found a median accuracy of 12.89 km (MAD 5.17) on animals. We found that robust real-time communication (median message delay of 1.49 s), the extremely small size of the tags (starting at 1.28 g without GPS), and the low power demands (as low as 5.8 µAh per transmitted byte) unlock new possibilities for ecological data collection and global animal observation.

Bio-telemetry from small tags attached to animals is one of the principal methods for studying the ecology and behaviour of wildlife. The field has constantly evolved over the last 80 years as technological improvement enabled a diversity of sensors to be integrated into the tags (e.g., GPS, accelerometers, etc.). However, retrieving data from tags on free-ranging animals remains a challenge since satellite and GSM networks are relatively expensive and or power hungry. Recently a new class of low-power communication networks have been developed and deployed worldwide to connect the internet of things (IoT). Here, we evaluated one of these, the Sigfox IoT network, for the potential as a real-time multi-sensor data retrieval and tag commanding system for studying fauna across a diversity of species and ecosystems. We tracked 312 individuals across 30 species (from 25 g bats to 3 t elephants) with seven different device concepts, resulting in more than 177,742 successful transmissions. We found a maximum line of sight communication distance of 280 km (on a flying cape vulture [Gyps coprotheres]), which sets a new documented record for animal-borne digital data transmission using terrestrial infrastructure. The average transmission success rate amounted to 68.3% (SD 22.1) on flying species and 54.1% (SD 27.4) on terrestrial species. In addition to GPS data, we also collected and transmitted data products from accelerometers, barometers, and thermometers. Further, we assessed the performance of Sigfox Atlas Native, a low-power method for positional estimates based on radio signal strengths and found a median accuracy of 12.89 km (MAD 5.17) on animals. We found that robust real-time communication (median message delay of 1.49 s), the extremely small size of the tags (starting at 1.28 g without GPS), and the low power demands (as low as 5.8 µAh per transmitted byte) unlock new possibilities for ecological data collection and global animal observation.

We discuss the mechanisms of photon-photon fusion triggering the dilepton production in proton-proton collisions with rapidity gap in the main detector and one forward proton in the forward proton detectors. This correspond to the LHC measurements made by ATLAS+AFP and CMS+PPS. Transverse momenta of the intermediate photons and photon fluxes expressed by the form factors and structure functions are included. Moreover the influence of proton measurement and cuts on the $\xi_{1/2}$, $M_{ll}$, $Y_{ll}$, $p_{t,ll}$ distributions, cross section and gap survival factor are considered for both double-elastic and single-dissociative processes. The analyzes used the SuperChic generator to calculate the soft gap survival factor and to compare the results obtained with its use to the results obtained on the owned codes available. It is shown that the gap survival factor for the single dissociative mechanism is related to the emission of a (mini)jet into the main detector depending on the type of contribution. The dependence between this value and the invariant mass as well as the transverse momentum of the leptons pair and its rapidity was also found., Comment: Presented at the Low-$x$ Workshop, Elba Island, Italy, September 27--October 1 2021

1) Harry Blatterer: Everyday Friendships - Intimacy as Freedom in a Complex World. Basingstoke: Palgrave Macmillan 2014. 9781137316400.+++2) Janosch Schobin, Vincenz Leuschner, Sabine Flick, Erika Alleweldt, Eric Anton Heuser, Agnes Brandt: Freundschaft heute - Eine Einführung in die Freundschaftssoziologie (mit Gastbeiträgen von Andrea Knecht, Christian Kühner und Kai Marquardsen). Bielefeld: transcript Verlag 2016. 9783837635508

Academic data sharing is a way for researchers to collaborate and thereby meet the needs of an increasingly complex research landscape. It enables researchers to verify results and to pursuit new research questions with "old" data. It is therefore not surprising that data sharing is advocated by funding agencies, journals, and researchers alike. We surveyed 2661 individual academic researchers across all disciplines on their dealings with data, their publication practices, and motives for sharing or withholding research data. The results for 1564 valid responses show that researchers across disciplines recognise the benefit of secondary research data for their own work and for scientific progress as a whole - still they only practice it in moderation. An explanation for this evidence could be an academic system that is not driven by monetary incentives, nor the desire for scientific progress, but by individual reputation - expressed in (high ranked journal) publications. We label this system a Reputation Economy. This special economy explains our findings that show that researchers have a nuanced idea how to provide adequate formal recognition for making data available to others - namely data citations. We conclude that data sharing will only be widely adopted among research professionals if sharing pays in form of reputation. Thus, policy measures that intend to foster research collaboration need to understand academia as a reputation economy. Successful measures must value intermediate products, such as research data, more highly than it is the case now.

We analyze the photon-initiated processes for production of $ e ^ + e ^- $ pairs in proton-nucleus collisions at LHC energy, taking into account both elastic processes and proton dissociations in the low-mass region (LMR) and intermediate-mass region (IMR) as defined by the ALICE collaboration. The calculations are performed within the $k_{\rm T}$-factorisation approach, including transverse momenta of intermediate photons. We discuss several differential distributions in invariant mass of both the leptons $M_{ll}$, pair rapidity $Y_{ll}$ and transverse momenta of the lepton pair $p_{t,ll}$. In addition, we present the two-dimensional distributions in $\log_{10} x_{Bj}$ and $\log_{10} Q^{2}$ and ($\log_{10} W,\log_{10} Q^{2}$) the arguments of the deep-inelastic structure functions. All presented results were obtained with modern parametrizations of proton structure functions. Limiting to small invariant masses of dielectrons one tests structure functions in the nonperturbative region of small $Q^2$ and/or small $W$. We quantify difference for different parametrizations from the literature., Comment: 13 pages, 10 figures

Bird migrations are impressive behavioral phenomena, representing complex spatiotemporal strategies to balance costs of living while maximizing fitness. The field of bird migration research has made great strides over the past decades, yet fundamental gaps remain. Technologies have sparked a transformation in the study of bird migration research by revealing remarkable insights into the underlying behavioral, cognitive, physiological and evolutionary mechanisms of these diverse journeys. Here, we aim to encourage broad discussions and promote future studies by highlighting research fields that are characterized by major knowledge gaps or conflicting evidence, namely the fields of navigation, social learning, individual development, energetics and conservation. We approach each topic by summarizing the current state of knowledge and provide a future outlook of ideas and state-of-the-art methods to further advance the field. Integrating knowledge across these disciplines will allow us to understand the adaptive abilities of different species and to develop effective conservation strategies in a rapidly changing world.

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmental change.

A 4-month-old female Irish Terrier presented with a well demarcated ulcerative and crusting lesion in the right ear canal. Histological analysis revealed epidermal hyperplasia with severe acantholysis affecting all suprabasal layers of the epidermis, which prompted a presumptive diagnosis of canine Darier disease. The lesion was successfully treated by repeated laser ablation of the affected epidermis. Over the course of three years, the dog additionally developed three dermal nodules of up to 4 cm in diameter that were excised and healed without complications. Histology of the excised tissue revealed multiple infundibular cysts extending from the upper dermis to the subcutis. The cysts were lined by squamous epithelium, which presented with abundant acantholysis of suprabasal keratinocytes. Infundibular cysts represent a novel finding not previously reported in Darier patients. Whole genome sequencing of the affected dog was performed, and the functional candidate genes for Darier disease (ATP2A2) and Hailey-Hailey disease (ATP2C1) were investigated. The analysis revealed a heterozygous SINE insertion into the ATP2A2 gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the ATP2A2 mRNA from skin of the affected dog demonstrated a splicing defect and marked allelic imbalance, suggesting nonsense-mediated decay of the resulting aberrant transcripts. As Darier disease in humans is caused by haploinsufficiency of ATP2A2, our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease.

We discuss the mechanism of dilepton production in proton-proton scattering via fusion of virtual photons with identification of one proton on either side. This is relevant for the ATLAS+AFP and CMS+PPS at the LHC. Transverse momenta of the photons are taken into account via photon unintegrated fluxes. The latter ones are expressed in terms of proton electromagnetic form factors and structure functions. We include different categories of such processes (double elastic, single dissociative). Some differential distributions are shown explicitly and differences with respect to the results without proton identification are discussed. A soft gap survival factor is calculated using SuperChic-4 code., Comment: 7 pages, 6 figures a talk presented by A. Szczurek at the EPS-HEP 2021 conference, Hamburg, July 26-30 2021

We discuss photon-photon fusion mechanisms of dilepton production in proton-proton collisions with rapidity gap in the main detector and one forward proton in the forward proton detectors. This is relevant for the LHC measurements by ATLAS+AFP and CMS+PPS. Transverse momenta of the intermediate photons are taken into account and photon fluxes are expressed in terms of proton electromagnetic form factors and structure functions. Both double-elastic and single-dissociative processes are included in the analysis. Different parametrizations of the structure functions are used. Some differential distributions are presented. Some differences with respect to the results without proton measurement are discussed., Comment: Submission to SciPost, presented by A. Szczurek at XXVIII International Workshop on Deep-Inelastic Scattering and Related Subjects 12-16 April 2021, Stony Brook, NY

We discuss photon-photon fusion mechanisms of dilepton production in proton-proton collisions with rapidity gap in the main detector and one forward proton in the forward proton detectors. This is relevant for the LHC measurements by ATLAS+AFP and CMS+PPS. Transverse momenta of the intermediate photons are taken into account and photon fluxes are expressed in terms of proton electromagnetic form factors and structure functions. Differential distributions in $\xi_{1/2}$, $M_{ll}$, $Y_{ll}$, $p_{t,ll}$, $M_R$ %pamietac wyjasnic M_R w tekscie are shown and the competition of different mechanisms is discussed. Both double-elastic and single-dissociative processes are included in the analysis. Different parametrizations of the structure functions are used. We discuss also mechanism with one forward $\Delta^+$ isobar, or other proton resonances in the final state. The role of several cuts is studied. We also use SuperChic generator and compare corresponding results to the results of our codes. The soft rapidity gap survival factor is calculated for each contribution separately. The gap survival factor for the single-dissociative mechanism due to minijet emission into the main detector is calculated in addition. It depends on the type of contribution (fully elastic, single dissociation, double dissociation). The soft rapidity gap survival factor for the case of single proton measurement is significantly smaller than that for the inclusive case (no proton measurement). We find only weak dependence on the invariant mass of the dilepton system as well as the lepton pair transverse momentum and sizeable dependence on the pair rapidity. The latter effect is rather difficult to identify experimentally., Comment: 33 pages, 30 figures, 3 tables

Cutaneous lupus erythematosus (CLE) in humans encompasses multiple subtypes that exhibit a wide array of skin lesions and, in some cases, are associated with the development of systemic lupus erythematosus (SLE). We investigated dogs with exfoliative cutaneous lupus erythematosus (ECLE), a dog-specific form of chronic CLE that is inherited as a monogenic autosomal recessive trait. A genome-wide association study (GWAS) with 14 cases and 29 controls confirmed a previously published result that the causative variant maps to chromosome 18. Autozygosity mapping refined the ECLE locus to a 493 kb critical interval. Filtering of whole genome sequence data from two cases against 654 controls revealed a single private protein-changing variant in this critical interval, UNC93B1:c.1438C>A or p.Pro480Thr. The homozygous mutant genotype was exclusively observed in 23 ECLE affected German Shorthaired Pointers and an ECLE affected Vizsla, but absent from 845 controls. UNC93B1 is a transmembrane protein located in the endoplasmic reticulum and endolysosomes, which is required for correct trafficking of several Toll-like receptors (TLRs). The p.Pro480Thr variant is predicted to affect the C-terminal tail of the UNC93B1 that has recently been shown to restrict TLR7 mediated autoimmunity via an interaction with syndecan binding protein (SDCBP). The functional knowledge on UNC93B1 strongly suggests that p.Pro480Thr is causing ECLE in dogs. These dogs therefore represent an interesting spontaneous model for human lupus erythematosus. Our results warrant further investigations of whether genetic variants affecting the C-terminus of UNC93B1 might be involved in specific subsets of CLE or SLE cases in humans and other species.

Cutaneous lupus erythematosus (CLE) in humans encompasses multiple subtypes that exhibit a wide array of skin lesions and, in some cases, are associated with the development of systemic lupus erythematosus (SLE). We investigated dogs with exfoliative cutaneous lupus erythematosus (ECLE), a dog-specific form of chronic CLE that is inherited as a monogenic autosomal recessive trait. A genome-wide association study (GWAS) with 14 cases and 29 controls confirmed a previously published result that the causative variant maps to chromosome 18. Autozygosity mapping refined the ECLE locus to a 493 kb critical interval. Filtering of whole genome sequence data from two cases against 654 controls revealed a single private protein-changing variant in this critical interval, UNC93B1:c.1438C>A or p.Pro480Thr. The homozygous mutant genotype was exclusively observed in 23 ECLE affected German Shorthaired Pointers and an ECLE affected Vizsla, but absent from 845 controls. UNC93B1 is a transmembrane protein located in the endoplasmic reticulum and endolysosomes, which is required for correct trafficking of several Toll-like receptors (TLRs). The p.Pro480Thr variant is predicted to affect the C-terminal tail of the UNC93B1 that has recently been shown to restrict TLR7 mediated autoimmunity via an interaction with syndecan binding protein (SDCBP). The functional knowledge on UNC93B1 strongly suggests that p.Pro480Thr is causing ECLE in dogs. These dogs therefore represent an interesting spontaneous model for human lupus erythematosus. Our results warrant further investigations of whether genetic variants affecting the C-terminus of UNC93B1 might be involved in specific subsets of CLE or SLE cases in humans and other species.

Recent advances in microscopy, computing power and image processing have enabled the analysis of ever larger datasets of movies of microorganisms to study their behaviour. However, techniques for analysing the dynamics of individual cells from such datasets are not yet widely available in the public domain. We recently demonstrated significant phenotypic heterogeneity in the adhesion of Escherichia coli bacteria to glass surfaces using a new method for the high-throughput analysis of video microscopy data. Here, we present an in-depth analysis of this method and its limitations, and make public our algorithms for following the positions and orientations of individual rod-shaped bacteria from time-series of 2D images to reconstruct their trajectories and characterise their dynamics. We demonstrate in detail how to use these algorithms to identify different types of adhesive dynamics within a clonal population of bacteria sedimenting onto a surface. The effects of measurement errors in cell positions and of limited trajectory durations on our results are discussed.

When designing the individual subassemblies of machines or entire devices one has to draw special attention to the resistance of the elements working there, to tribological damages (mechanical, fatigue, adhesion, abrasion, hydrogen and other damages) as well as to non-tribological damages (corrosion, diffusion, cavitation, erosion, ablation and others). The main purpose of this publication was to examine the influence of the applied WC/C protective coating deposited by PVD method on the cavitation wear processes of construction elements working in difficult cavitation environment. Two steels were selected for detailed examinations in the conditions of cavitation wear. The first one is P265GH steel commonly used for pressure devices working at elevated temperatures, with a ferritic-pearlitic structure, and the other derives from a group of stainless steels, i.e. chromium-nickel X2CrNi18-9 (304L) steel with an austenitic structure. The tests results obtained allow to conclude that the application of special low-friction protective coatings allows to reduce costs associated with selection of engineering materials for a substrate of constructional elements working in a cavitation wear environment. P265GH steel is 4 times cheaper than austenitic chromium-nickel X2CrNi18-9 steel, and if a WC/C coating is deposited in this case, this considerably extends the working time of such elements in a cavitation environment.

Das bologna.lab der Humboldt-Universität zu Berlin fördert im Rahmen des Qualitätspakts Lehre (BMBF, 2012-2020) eine Reihe von Projekten mit dem Ziel, bereits ab dem Bachelorstudium Freiräume für forschendes Lernen zu schaffen und diese mit forschungsnahen Lehrangeboten zu füllen. Eines dieser Projekte sind die Q-Tutorien, deren Abschlussberichte in diesem Band versammelt sind. In diesen studentischen Veranstaltungen bearbeitet eine Gruppe Studierender ein selbst gewähltes Forschungsthema in eigenständiger, interdisziplinärer und möglichst innovativer Projektarbeit.

When designing the individual subassemblies of machines or entire devices one has to draw special attention to the resistance of the elements working there, to tribological damages (mechanical, fatigue, adhesion, abrasion, hydrogen and other damages) as well as to non-tribological damages (corrosion, diffusion, cavitation, erosion, ablation and others). The main purpose of this publication was to examine the influence of the applied WC/C protective coating deposited by PVD method on the cavitation wear processes of construction elements working in difficult cavitation environment. Two steels were selected for detailed examinations in the conditions of cavitation wear. The first one is P265GH steel commonly used for pressure devices working at elevated temperatures, with a ferritic-pearlitic structure, and the other derives from a group of stainless steels, i.e. chromium-nickel X2CrNi18-9 (304L) steel with an austenitic structure. The tests results obtained allow to conclude that the application of special low-friction protective coatings allows to reduce costs associated with selection of engineering materials for a substrate of constructional elements working in a cavitation wear environment. P265GH steel is 4 times cheaper than austenitic chromium-nickel X2CrNi18-9 steel, and if a WC/C coating is deposited in this case, this considerably extends the working time of such elements in a cavitation environment.

Das bologna.lab der Humboldt-Universität zu Berlin fördert im Rahmen des Qualitätspakts Lehre (BMBF, 2012-2020) eine Reihe von Projekten mit dem Ziel, bereits ab dem Bachelorstudium Freiräume für forschendes Lernen zu schaffen und diese mit forschungsnahen Lehrangeboten zu füllen. Eines dieser Projekte sind die Q-Tutorien, deren Abschlussberichte in diesem Band versammelt sind. In diesen studentischen Veranstaltungen bearbeitet eine Gruppe Studierender ein selbst gewähltes Forschungsthema in eigenständiger, interdisziplinärer und möglichst innovativer Projektarbeit.

We report on the development and performance of advanced Nb nanoSQUIDs for magnetization reversal studies on individual magnetic nanoparticles (MNPs). The nanoSQUIDs are based on trilayer Nb/HfTi/Nb Josephson junctions exhibiting large critical current densities >105 A/cm2 at 4.2 K. This offers the unique advantage of combining the realization of SQUIDs with very small loop inductance, and hence ultra-low flux noise, with a superconductor multilayer approach that enables the fabrication of complex devices with significantly increased functionality for various applications. One example is the recently developed 3-axis vector nanoSQUID. This device consists of three mutually orthogonal SQUIDs (Fig.1) that allow simultaneous and independent detection of the three components of the vector magnetic moment of individual MNPs at 4.2 K in applied magnetic fields up to ~150 mT. We present the performance of improved vector nanoSQUIDs and first attempts to vectorially detect the magnetization reversal of individual Co MNPs deposited onto our devices by focused electron beam induced deposition.

Most bacteria swim in liquid environments by rotating one or several flagella. The long external filament of the flagellum is connected to a membrane-embedded basal body by a flexible universal joint, the hook, which allows the transmission of motor torque to the filament. The length of the hook is controlled on a nanometer scale by a sophisticated molecular ruler mechanism. However, why its length is stringently controlled has remained elusive. We engineered and studied a diverse set of hook- length variants of Salmonella enterica. Measurements of plate-assay motility, single- cell swimming speed, and directional persistence in quasi-2D and population- averaged swimming speed and body angular velocity in 3D revealed that the motility performance is optimal around the wild-type hook length. We conclude that too-short hooks may be too stiff to function as a junction and too-long hooks may buckle and create instability in the flagellar bundle. Accordingly, peritrichously flagellated bacteria move most efficiently as the distance travelled per body rotation is maximal and body wobbling is minimized. Thus, our results suggest that the molecular ruler mechanism evolved to control flagellar hook growth to the optimal length consistent with efficient bundle formation. The hook-length control mechanism is therefore a prime example of how bacteria evolved elegant but robust mechanisms to maximize their fitness under specific environmental constraints.

Coat color dilution in dogs is a specific pigmentation phenotype caused by a defective transport of melanosomes leading to large clumps of pigment. It is inherited as a Mendelian autosomal recessive trait and may be accompanied by hair loss, the so-called color dilution alopecia (CDA), or black hair follicular dysplasia (BHFD). We previously identified the noncoding c.-22G>A transition in the melanophilin gene (MLPH) as a candidate causative mutation for the dilute phenotype. We have now extended our study and genotyped 935 dogs from 20 breeds segregating for dilute coat color. The dilute-associated A allele segregates in many different breeds suggesting an old mutation event. We also investigated skin biopsies of dogs suspected of having either CDA or BHFD, and our data clearly indicate that the dilute mutation is required but not sufficient to develop clinical signs of the disease. The risk to develop CDA/BHFD seems to be breed specific. Interestingly, 22 out of 29 dogs with clinical signs of CDA/BHFD have clumped melanin in the epidermis, the follicular epithelium, and the hair shafts, whereas in dilute dogs without clinical disease, clumped melanin is only found in the follicular epithelium and the hair shafts but not in the epidermis

This article describes a multi-method approach for usability testing. The approach combines paper prototyping and think-aloud with two supplemental methods: advanced scribbling and a handicraft task. The method of advanced scribbling instructs the participants to use different colors for marking important, unnecessary and confusing elements in a paper prototype. In the handicraft task the participants have to tinker a paper prototype of their wish version. Both methods deliver additional information on the needs and expectations of the potential users and provide helpful indicators for clarifying complex or contradictory findings. The multi-method approach and its surplus benefit are illustrated by a pilot study on the redesign of the homepage of a library 2.0. The findings provide positive evidence for the applicability of the advanced scribbling and the handicraft task as well as for the surplus merit of the multi-method approach. The article closes with a discussion and outlook. (author's abstract), In diesem Artikel wird ein multi-methodischer Ansatz beschrieben, der Paper Prototyping mit zwei zusätzlichen Methoden kombiniert, dem Advanced Scribbling und einem Handicraft Task. Beim Advanced Scribbling [erweitertes, fortgeschrittenes Kritzeln] werden die Untersuchungsteilnehmer/innen instruiert, wichtige, überflüssige und verwirrende Elemente eines Papier-Prototypen mit jeweils unterschiedlichen Farben zu markieren. Für das Handicraft Task [Bastelaufgabe] sollen sie ihre eigene Wunschversion als Papier-Prototyp anfertigen. Beide Methoden liefern zusätzliche Informationen über die Bedürfnisse und Erwartungen der potenziellen Endnutzer/innen und bieten hilfreiche Indikatoren zur Klärung von komplexen oder widersprüchlichen Ergebnissen. Der multi-methodische Ansatz und sein zusätzlicher Mehrwert werden anhand einer Pilot-Studie zur Neugestaltung der Homepage einer modernen Bibliothek (Library 2.0) illustriert. Die Ergebnisse stützen die praktische Anwendbarkeit des Advanced Scribblings und des Handicraft Tasks und liefern zudem positive Evidenz für den Mehrwert des multi-methodischen Ansatzes. Der Artikel schließt mit einer Diskussion und einem Ausblick. (Autorenreferat)

Academic data sharing is a way for researchers to collaborate and thereby meet the needs of an increasingly complex research landscape. It enables researchers to verify results and to pursuit new research questions with "old" data. It is therefore not surprising that data sharing is advocated by funding agencies, journals, and researchers alike. We surveyed 2661 individual academic researchers across all disciplines on their dealings with data, their publication practices, and motives for sharing or withholding research data. The results for 1564 valid responses show that researchers across disciplines recognise the benefit of secondary research data for their own work and for scientific progress as a whole-still they only practice it in moderation. An explanation for this evidence could be an academic system that is not driven by monetary incentives, nor the desire for scientific progress, but by individual reputation-expressed in (high ranked journal) publications. We label this system a Reputation Economy. This special economy explains our findings that show that researchers have a nuanced idea how to provide adequate formal recognition for making data available to others-namely data citations. We conclude that data sharing will only be widely adopted among research professionals if sharing pays in form of reputation. Thus, policy measures that intend to foster research collaboration need to understand academia as a reputation economy. Successful measures must value intermediate products, such as research data, more highly than it is the case now.

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.

Objectives: To discuss characteristic pathologic and radiologic correlates of tumor invasiveness in lung adenocarcinoma and their associated clinical implications. To describe current advances in cancer biology related to the acquisition of tumor invasion and metastasis. To identify areas for further research which have clinical impact for prognostication and treatment of early stage lung cancer. Overall Goals and Objectives: Following this activity, a participant should be able to: 1. Recognize recent advances and developments in Pulmonary Medicine & Critical Care and translate into clinical practice 2. Integrate perspectives of multiple disciplines into decision-making on behalf of patients through structured plans for patient care. 3. Develop areas for future research and discuss appropriate methods to address these needs. 4. Summarize and continually improve communications as a team, caring for Pulmonary/Critical Care patients. PowerPoint slides only, no audio.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4x10(-14)). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38x coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4x10(-14)). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38x coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4x10(-14)). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38x coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4x10(-14)). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38x coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4x10(-14)). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38x coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): B07103, doi:10.1029/2010JB007931., Expeditions 304 and 305 of the Integrated Ocean Drilling Program cored and logged a 1.4 km section of the domal core of Atlantis Massif. Postdrilling research results summarized here constrain the structure and lithology of the Central Dome of this oceanic core complex. The dominantly gabbroic sequence recovered contrasts with predrilling predictions; application of the ground truth in subsequent geophysical processing has produced self-consistent models for the Central Dome. The presence of many thin interfingered petrologic units indicates that the intrusions forming the domal core were emplaced over a minimum of 100–220 kyr, and not as a single magma pulse. Isotopic and mineralogical alteration is intense in the upper 100 m but decreases in intensity with depth. Below 800 m, alteration is restricted to narrow zones surrounding faults, veins, igneous contacts, and to an interval of locally intense serpentinization in olivine-rich troctolite. Hydration of the lithosphere occurred over the complete range of temperature conditions from granulite to zeolite facies, but was predominantly in the amphibolite and greenschist range. Deformation of the sequence was remarkably localized, despite paleomagnetic indications that the dome has undergone at least 45° rotation, presumably during unroofing via detachment faulting. Both the deformation pattern and the lithology contrast with what is known from seafloor studies on the adjacent Southern Ridge of the massif. There, the detachment capping the domal core deformed a 100 m thick zone and serpentinized peridotite comprises ∼70% of recovered samples. We develop a working model of the evolution of Atlantis Massif over the past 2 Myr, outlining several stages that could explain the observed similarities and differences between the Central Dome and the Southern Ridge.

Expeditions 304 and 305 of the Integrated Ocean Drilling Program cored and logged a 1.4 km section of the domal core of Atlantis Massif. Postdrilling research results summarized here constrain the structure and lithology of the Central Dome of this oceanic core complex. The dominantly gabbroic sequence recovered contrasts with predrilling predictions; application of the ground truth in subsequent geophysical processing has produced self-consistent models for the Central Dome. The presence of many thin interfingered petrologic units indicates that the intrusions forming the domal core were emplaced over a minimum of 100–220 kyr, and not as a single magma pulse. Isotopic and mineralogical alteration is intense in the upper 100 m but decreases in intensity with depth. Below 800 m, alteration is restricted to narrow zones surrounding faults, veins, igneous contacts, and to an interval of locally intense serpentinization in olivine-rich troctolite. Hydration of the lithosphere occurred over the complete range of temperature conditions from granulite to zeolite facies, but was predominantly in the amphibolite and greenschist range. Deformation of the sequence was remarkably localized, despite paleomagnetic indications that the dome has undergone at least 45° rotation, presumably during unroofing via detachment faulting. Both the deformation pattern and the lithology contrast with what is known from seafloor studies on the adjacent Southern Ridge of the massif. There, the detachment capping the domal core deformed a 100 m thick zone and serpentinized peridotite comprises ∼70% of recovered samples. We develop a working model of the evolution of Atlantis Massif over the past 2 Myr, outlining several stages that could explain the observed similarities and differences between the Central Dome and the Southern Ridge.

Expeditions 304 and 305 of the Integrated Ocean Drilling Program cored and logged a 1.4 km section of the domal core of Atlantis Massif. Postdrilling research results summarized here constrain the structure and lithology of the Central Dome of this oceanic core complex. The dominantly gabbroic sequence recovered contrasts with predrilling predictions; application of the ground truth in subsequent geophysical processing has produced self-consistent models for the Central Dome. The presence of many thin interfingered petrologic units indicates that the intrusions forming the domal core were emplaced over a minimum of 100-220 kyr, and not as a single magma pulse. Isotopic and mineralogical alteration is intense in the upper 100 m but decreases in intensity with depth. Below 800 m, alteration is restricted to narrow zones surrounding faults, veins, igneous contacts, and to an interval of locally intense serpentinization in olivine-rich troctolite. Hydration of the lithosphere occurred over the complete range of temperature conditions from granulite to zeolite facies, but was predominantly in the amphibolite and greenschist range. Deformation of the sequence was remarkably localized, despite paleomagnetic indications that the dome has undergone at least 45 rotation, presumably during unroofing via detachment faulting. Both the deformation pattern and the lithology contrast with what is known from seafloor studies on the adjacent Southern Ridge of the massif. There, the detachment capping the domal core deformed a 100 m thick zone and serpentinized peridotite comprises ∼70% of recovered samples. We develop a working model of the evolution of Atlantis Massif over the past 2 Myr, outlining several stages that could explain the observed similarities and differences between the Central Dome and the Southern Ridge.