julilili42/papers huggingface dataset:
Collaborative Consumption, Sozialkapital und Quartier. Eine Annäherung
2014-08-04

Both, neighbourhoods and Collaborative Consumption (sometimes also referred to as Sharing Economy or New Economy), are the loci of interest in current scientific and political discussions that oscillate between the global and the local. This article aims to link the concepts’ potential procedural similarities more closely than has been done so far. Both of these concepts consider societal problems and potentials to be affecting the micro level; they form a part of the currently undergoing local shift. In order to explore this potential in more detail, we will present a typology of different platforms of Collaborative Consumption that takes into consideration both, social capital and relevant characteristics of a neighbourhood. Based on this analysis, we will argue that many of these platforms, despite their emphasis on neighbourly relationships, don’t necessarily foster an accumulation of social capital within neighbourhoods. However, there is one distinguished type, we define it as “the autotelic-oriented one”, which can potentially have a positive impact on neighbourhood development. Only this type enables the accumulation of social capital, attempts to overcome socio-economic barriers and provides reciprocity mechanisms for the exchange of favours. This type could be fruitful for neighbourhoods and should be taken into account more seriously by researchers and professionals in this field. We will argue that Collaborative Consumption can hence result in a “neighbourhood 2.0” – a community that is complementarily strengthened through web-based services.
Seismic wave propagation in anisotropic ice – Part 2: Effects of crystal anisotropy in geophysical data
2014-08-04

Abstract. We investigate the propagation of seismic waves in anisotropic ice. Two effects are important: (i) sudden changes in crystal orientation fabric (COF) lead to englacial reflections; (ii) the anisotropic fabric induces an angle dependency on the seismic velocities and, thus, recorded traveltimes. Velocities calculated from the polycrystal elasticity tensor derived for the anisotropic fabric from measured COF eigenvalues of the EDML ice core, Antarctica, show good agreement with the velocity trend determined from a vertical seismic profiling. The agreement of the absolute velocity values, however, depends on the choice of the monocrystal elasticity tensor used for the calculation of the polycrystal properties. With this validation of seismic velocities we make use of abrupt changes in COF as common reflection mechanism for seismic and radar data below the firn–ice transition to investigate their occurrence by comparison with ice-core data. Our results highlight the possibility to complement regional radar surveys with local, surface-based seismic deployment to separate isochrones in radar data from other mechanisms. This is important for the reconnaissance of future ice-core drill sites, where accurate isochrone (i.e. non-COF) layer integrity allows for synchronization with other cores, as well as studies of ice dynamics considering non-homogeneous viscosity from preferred crystal orientations.
Semisynthesis and optimization of G protein‐coupled receptor mimics
2014-08-04

We have recently developed a soluble mimic of the corticotropin‐releasing factor receptor type 1 (CRF1), a membrane‐spanning G protein‐coupled receptor, which allowed investigations on receptor–ligand interactions. The CRF1 mimic consists of the receptor N ‐terminus and three synthetic extracellular loops (ECL1–3), which constitute the extracellular receptor domains (ECDs) of CRF1, coupled to a linear peptide template. Here, we report the synthesis of a modified CRF1 mimic, which is more similar to the native receptor possessing a cyclic template that displays the ECDs in a more physiological conformation compared with the initial linear design. In order to facilitate detailed biophysical investigations on CRF1 mimics, we have further established a cost‐efficient access to the CRF1 mimic, which is suitable for isotopic labeling for NMR spectroscopy. To this end, the loop‐mimicking cyclic peptide of the ECL2 of CRF1 was produced recombinantly and cyclized by expressed protein ligation. Cyclic ECL2 was obtained in milligram scale, and CRF1 mimics synthesized from this material displayed the same binding properties as synthetic CRF1 constructs. Copyright © 2014 European Peptide Society and John Wiley &amp; Sons, Ltd.
Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer
2014-08-05

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R(2): 53%, P<10(-77)). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43-0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04-4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS.
Dopamine modulation of learning and memory in the prefrontal cortex: insights from studies in primates, rodents, and birds
2014-08-05

In this review, we provide a brief overview over the current knowledge about the role of dopamine transmission in the prefrontal cortex during learning and memory. We discuss work in humans, monkeys, rats, and birds in order to provide a basis for comparison across species that might help identify crucial features and constraints of the dopaminergic system in executive function. Computational models of dopamine function are introduced to provide a framework for such a comparison. We also provide a brief evolutionary perspective showing that the dopaminergic system is highly preserved across mammals. Even birds, following a largely independent evolution of higher cognitive abilities, have evolved a comparable dopaminergic system. Finally, we discuss the unique advantages and challenges of using different animal models for advancing our understanding of dopamine function in the healthy and diseased brain.
Frequency of AIP Gene Mutations in Young Patients With Acromegaly: A Registry-Based Study
2014-08-05

Context: Familial and sporadic GH-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) tend to have more aggressive tumors occurring at a younger age. Objective: The objective of the study was to investigate the frequency of AIPmut in patients diagnosed at 30 years of age or younger. Design: The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at 30 years of age or younger (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis. Intervention: DNA was analyzed by direct sequencing and multiplex ligation dependent probe amplification Main outcome Measures: The number of patients with AIPmut was measured. Results: Five patients had either a mutation (c.490C&amp;gt;T, c.844C&amp;gt;T, and c.911G&amp;gt;A, three males) or gross deletions of exons 1 and 2 of the AIP gene (n = 2, one female). The overall frequency of an AIPmut was 5.5%, and 2.3% or 2.4% in patients with an apparently sporadic adenoma or macroadenoma, respectively. By contrast, three of four patients (75%) with a positive family history were tested positive for an AIPmut. Except for a positive family history, there were no significant differences between patients with and without an AIPmut. Conclusions: The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, whereas young patients without an apparent family history should be screened, depending on the individual cost to benefit ratio.
VAD as Bridge to Recovery in Anthracycline-Induced Cardiomyopathy and HHV6 Myocarditis
2014-08-05

This report describes an 8-year-old child with acute anthracycline-induced cardiomyopathy triggered by human herpesvirus 6 and the subsequent implantation of an intracorporeal continuous-flow left ventricular assist device (LVAD) and the process to discharge the child from the hospital. After barely 3 months on mechanical support, the device was explanted after thorough examination. Experiences regarding LVAD removal are limited, and no guidelines for echocardiographic and hemodynamic criteria for LVAD removal in children have been published thus far. We present our institutional algorithm for device selection, surveillance in an ambulatory setting, and testing for myocardial recovery, as well as our criteria for LVAD explantation in children.
A direct enzyme-linked immunosorbent assay (ELISA) for the quantitative evaluation of Janus Kinase 3 (JAK3) inhibitors
2014-08-05

The availability of a robust, precise and cost-efficient test system is the prerequisite for the performance of any medicinal chemistry program, especially in an academic environment. For the identification of novel Janus Kinase 3 inhibitors and determination of structure–activity relationships, a direct enzyme-linked immunosorbent assay was developed. Being applicable in a standard laboratory, the main advantage over existing methods is the basic equipment requirement as this assay does not need special handling originating from the use of cell cultures or radiometric readout. In contrast to earlier methods relying on two-step procedures, our assay uses a single peroxidase conjugated antibody to quantify and detect substrate phosphorylation. This optimized assay features a limit of detection of 0.032 μg mL−1, a wide dynamic range of 0.638 OD units and an appropriate Z′ factor of 0.66. The determined IC50 value for Tofacitinib was 3.5 ± 0.6 nM (n = 18). A detailed assay protocol custom-tailored for the JAK3 kinase domain and a step-by-step manual for optimizing specific assay conditions are presented. This ELISA primarily addresses researchers within the academic setting facing the task to identify lead structures and explore structure–activity relationships of JAK3 inhibitors at reasonable costs.
In vivo protein crystallization in living insect cells
2014-08-05

Spontaneous protein crystallization within living cells has been observed several times in nature, e.g. for storage proteins in seeds. In vivo crystal growth can also occur during gene over-expression, as particularly discovered in baculovirus-infected insect cells [1]. We have recently shown that these in vivo crystals represent valuable targets for structural biology after isolation from the cell. Applying serial crystallography techniques at an X-ray free-electron laser (XFEL) as well as using a highly brilliant synchrotron source, single crystal diffraction pattern were collected and combined to yield high-resolution structural information of the associated fully glycosylated protein [2,3]. So far, the cellular mechanisms involved in the in vivo crystallization process remain to be understood, preventing a more successful application of this novel approach. Thus, our study aims at identifying the parameters crucial for optimal crystal growth within baculovirus-infected Sf9 insect cells. Combining confocal microscopy with live-cell imaging techniques and compartment-specific staining methods, we systematically investigated the impact of the intracellular environment on in vivo crystallization by directing recombinant proteins into different cellular compartments using specific signal sequences. Moreover, the impact of cellular transport mechanisms and induced cellular stress on the quality and size of the in vivo crystals was investigated in detail. The presented results provide important insights into the process of protein crystallization within living cells and will therefore significantly contribute to increase the success rate for spontaneous crystal growth of other proteins. Considering that in vivo crystals represent highly suitable targets for structural biology, this approach offers exciting new possibilities for proteins that do not form crystals suitable for conventional X-ray diffraction in vitro.
A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies
2014-08-06

Even though BSI with ESBL-E is still rare in this high-risk population, colonization rates are substantial and vary considerably between centres. In-hospital transmission of ESBL-E as assessed by molecular typing was the exception.
Sex Differences in the Neuromagnetic Cortical Response to Biological Motion
2014-08-06

Body motion is a rich source of information for social interaction, and visual biological motion processing may be considered as a hallmark of social cognition. It is unclear, however, whether the social brain is sex specific. Here we assess sex impact on the magnetoencephalographic (MEG) cortical response to point-light human locomotion. Sex differences in the cortical MEG response to biological motion occur mostly over the right brain hemisphere. At early latencies, females exhibit a greater activation than males over the right parietal, left temporal, and right temporal cortex, a core of the social brain. At later latencies, the boosts of activation are greater in males over the right frontal and occipital cortices. The findings deliver the first evidence for gender-dependent modes in the time course and topography of the neural circuitry underpinning visual processing of biological motion. The outcome represents a framework for studying sex differences in the social brain in psychiatric and neurodevelopmental disorders.
Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation
2014-08-06

Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS).
Reinforced Active Middle Ear Implant Fixation in Incus Vibroplasty
2014-08-06

Auxiliary fixation of the FMT by reinforcing the attachment to the long incus process, in these experiments with the head of a Soft CliP stapes prosthesis, leads to enhanced mechanical and functional coupling, evidenced by lower vibroplasty thresholds and increased bandwidth together with reduced variability of the vibrational frequency responses of the stapes footplate and RW membrane.
The Archaeology of the Central African Rainforest: Its Current State
2014-08-06

It is the aim of this chapter to present an up-to-date review of the archaeology of the equatorial rainforest. Whenever necessary, it will reach beyond the forest to consider phenomena that might have been connected with its internal settlement history. Insofar as general stimuli and processes of a natural or cultural order are important to the settling of the forest by pottery-producing and farming people, we will even have to adopt a perspective that goes beyond Central Africa.
Response to Editorial Comment to Combination of lidocaine suppository and periprostatic nerve block during transrectal prostate biopsy: A prospective randomized trial
2014-08-06

What might have been the mechanism of pain reduction by combined anesthesia during the sampling part of the prostate biopsy? Was there an age-related difference in the perception of pain? What was the reason for including patients undergoing subsequent prostate biopsy? We want to clarify that in our opinion, the mechanism of pain reduction during sampling is in large part due to the synergistic effect of neurovascular bundle blockage aided by the lidocaine suppository that can reduce sensation in the anal canal. Above the dentate line there is no sensory innervation, resulting in less discomfort of the transrectal probe in the anal canal, especially for the apical biopsies requiring more erect of the probe. The age-related difference in the perception of pain was more conspicuous in the single substance group. No difference was detectable within group 3 (periprostatic nerve block and lidocaine suppository). The reason for including patients with subsequent biopsies was to show that, specifically in group 3, pain reduction was clearly better than that during the previous biopsies. The comment by Dr Salagierski on the general use of local anesthesia can only be supported. In our experience, there are still patients receiving prostate biopsies without any form of analgesia. This must not be carried out today, and is clearly obsolete. In our series, periprostatic injections, particularly around the area of the apex, without a lidocaine suppository were uncomfortable for the majority of the patients. In Hanusch Krankenhaus, Vienna, Austria, every patient undergoing a prostate biopsy receives combination therapy and has excellent outcomes. Even patients who underwent a re-biopsy under the same conditions were not worried. We recommend the combination of a lidocaine suppository and periprostatic nerve block, even in extended biopsies. The use of general anesthesia for prostate biopsies is indicated in perineal and/or saturation biopsies, but cannot be recommended for the large majority of men. Not only because of costs, but also the possible risks of general anesthesia, we believe that any form of sufficient local anesthesia should be recommended for the comfort of the patient and the time schedule of the procedure. None declared.
7th Santorini Conference “Biologie Prospective”Systems Medicine, Personalized Health and Therapy in collaboration with ESPT
2014-08-06

Background:We live in a time of rapidly changing environments.Independently as unique individuals, and collectively as families, communities and societies we must adapt to live in these environments.Survival is paramount.Yet, it is an inherent biological component of life to tend toward health.How do we highlight and support health when non-communicable, chronic diseases (NCDs) threaten the hearts, minds and bodies of individuals and governments alike?NCDs affect not only personal health, but also the public wellbeing and health economics.One cause for optimism is that the biological bedrock of many NCDs contains a common thread of inflammatory disregulation.A deeper and integrative understanding of the causes and conditions that lead to such disregulation can provide novel interventions that may successfully target diverse NCDs.At the individual and family levels, the co-created development of the human immune, nervous and microbiome systems provide a scientific framework on which to prototype solutions.We also live in a time where data generation has become significantly cheaper than data analysis/utilization.The trend is general, especially with unstructured data.Structuring data adequately is unaffordable.This is an unprecedented trend -one that life scientists have never faced before.In addition, decision-making -using such data as inputis increasingly interwoven with the data itself.Despite the existence of an unprecedented amount of data, there is actually not enough to be purely data-driven in most cases and interdependency of data matters (a lot).Objective: To explore the use of information and communication technologies to understand and discovering relationships pertaining to health and identifying critical points of intervention.Design: Two examples, one focused on largely unstructured and combined information and another focused on detailed molecular descriptions of gut-microbe interactions were developed dynamical models and the same underlying informatics infrastructure.Results: Using USA data for obesity it was shown that friendship networks are important in building weight perception, setting weight goals, and measuring social marginalization among adolescents and young adults.In gut infectious diseases structural models were generated and calibrated using literature with model fitting to the experimental data supporting in silico experiments to generate model-derived predictions for validation via wet experimental testing iteratively with the model to generate novel hypotheses.Conclusions: Because of the relational nature, coevolution and connectedness of human habitats, institutions, activities, health and food systems they represent a central concept for public policy/ health and individual health.Use of advanced information and communication technologies for studying, designing, anticipating or monitoring intervention effects provides new opportunities for sustainable health and health systems.
Encoding of social signals in all three electrosensory pathways ofEigenmannia virescens
2014-08-07

Extracting complementary features in parallel pathways is a widely used strategy for a robust representation of sensory signals. Weakly electric fish offer the rare opportunity to study complementary encoding of social signals in all of its electrosensory pathways. Electrosensory information is conveyed in three parallel pathways: two receptor types of the tuberous (active) system and one receptor type of the ampullary (passive) system. Modulations of the fish's own electric field are sensed by these receptors and used in navigation, prey detection, and communication. We studied the neuronal representation of electric communication signals (called chirps) in the ampullary and the two tuberous pathways of Eigenmannia virescens. We first characterized different kinds of chirps observed in behavioral experiments. Since Eigenmannia chirps simultaneously drive all three types of receptors, we studied their responses in in vivo electrophysiological recordings. Our results demonstrate that different electroreceptor types encode different aspects of the stimuli and each appears best suited to convey information about a certain chirp type. A decoding analysis of single neurons and small populations shows that this specialization leads to a complementary representation of information in the tuberous and ampullary receptors. This suggests that a potential readout mechanism should combine information provided by the parallel processing streams to improve chirp detectability.