julilili42/papers huggingface dataset:
Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43
2016-07-23

Unique molecular properties of species D adenoviruses (Ads)-the most diverse yet underexplored group of Ads-have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies.
Laboratory Simulation of an Iron(II)-rich Precambrian Marine Upwelling System to Explore the Growth of Photosynthetic Bacteria
2016-07-24

A conventional concept for the deposition of some Precambrian Banded Iron Formations (BIF) proceeds on the assumption that ferrous iron [Fe(II)] upwelling from hydrothermal sources in the Precambrian ocean was oxidized by molecular oxygen [O2] produced by cyanobacteria. The oldest BIFs, deposited prior to the Great Oxidation Event (GOE) at about 2.4 billion years (Gy) ago, could have formed by direct oxidation of Fe(II) by anoxygenic photoferrotrophs under anoxic conditions. As a method for testing the geochemical and mineralogical patterns that develop under different biological scenarios, we designed a 40 cm long vertical flow-through column to simulate an anoxic Fe(II)-rich marine upwelling system representative of an ancient ocean on a lab scale. The cylinder was packed with a porous glass bead matrix to stabilize the geochemical gradients, and liquid samples for iron quantification could be taken throughout the water column. Dissolved oxygen was detected non-invasively via optodes from the outside. Results from biotic experiments that involved upwelling fluxes of Fe(II) from the bottom, a distinct light gradient from top, and cyanobacteria present in the water column, show clear evidence for the formation of Fe(III) mineral precipitates and development of a chemocline between Fe(II) and O2. This column allows us to test hypotheses for the formation of the BIFs by culturing cyanobacteria (and in the future photoferrotrophs) under simulated marine Precambrian conditions. Furthermore we hypothesize that our column concept allows for the simulation of various chemical and physical environments - including shallow marine or lacustrine sediments.
Laboratory Simulation of an Iron(II)-rich Precambrian Marine Upwelling System to Explore the Growth of Photosynthetic Bacteria
2016-07-24

A conventional concept for the deposition of some Precambrian Banded Iron Formations (BIF) proceeds on the assumption that ferrous iron [Fe(II)] upwelling from hydrothermal sources in the Precambrian ocean was oxidized by molecular oxygen [O2] produced by cyanobacteria. The oldest BIFs, deposited prior to the Great Oxidation Event (GOE) at about 2.4 billion years (Gy) ago, could have formed by direct oxidation of Fe(II) by anoxygenic photoferrotrophs under anoxic conditions. As a method for testing the geochemical and mineralogical patterns that develop under different biological scenarios, we designed a 40 cm long vertical flow-through column to simulate an anoxic Fe(II)-rich marine upwelling system representative of an ancient ocean on a lab scale. The cylinder was packed with a porous glass bead matrix to stabilize the geochemical gradients, and liquid samples for iron quantification could be taken throughout the water column. Dissolved oxygen was detected non-invasively via optodes from the outside. Results from biotic experiments that involved upwelling fluxes of Fe(II) from the bottom, a distinct light gradient from top, and cyanobacteria present in the water column, show clear evidence for the formation of Fe(III) mineral precipitates and development of a chemocline between Fe(II) and O2. This column allows us to test hypotheses for the formation of the BIFs by culturing cyanobacteria (and in the future photoferrotrophs) under simulated marine Precambrian conditions. Furthermore we hypothesize that our column concept allows for the simulation of various chemical and physical environments — including shallow marine or lacustrine sediments.
Multiplexed coding by cerebellar Purkinje neurons
2016-07-25

Purkinje cells (PC), the sole output neurons of the cerebellar cortex, encode sensorimotor information, but how they do it remains a matter of debate. Here we show that PCs use a multiplexed spike code. Synchrony/spike time and firing rate encode different information in behaving monkeys during saccadic eye motion tasks. Using the local field potential (LFP) as a probe of local network activity, we found that infrequent pause spikes, which initiated or terminated intermittent pauses in simple spike trains, provide a temporally reliable signal for eye motion onset, with strong phase-coupling to the β/γ band LFP. Concurrently, regularly firing, non-pause spikes were weakly correlated with the LFP, but were crucial to linear encoding of eye movement kinematics by firing rate. Therefore, PC spike trains can simultaneously convey information necessary to achieve precision in both timing and continuous control of motion.
Analgesia and Sedation Protocol for Mechanically Ventilated Postsurgical Children Reduces Benzodiazepines and Withdrawal Symptoms—But Not in All Patients
2016-07-25

Background We demonstrated recently that the implementation of a nurse-driven analgesia and sedation protocol (pediatric analgesia and sedation protocol [pASP]) for mechanically ventilated nonpostsurgical patients reduces the total dose of benzodiazepines and the withdrawal symptoms significantly. It has not been investigated if these results can also be expected in the group of patients undergoing surgery. Objectives To evaluate the effects of the pASP in mechanically ventilated postsurgical children regarding drug dosage, duration of mechanical ventilation, length of stay, and rate of withdrawal symptoms. Methods This is a two-phase prospective observational control study. The preimplementation group was managed by the physician's order and the postimplementation group was managed with the pASP including COMFORT-B, nurse interpretation of sedation, and Sophia observation withdrawal symptoms scale scoring. Measurements and Main Results One hundred and sixteen patients were included before and one hundred and ten patients after implementation. The pASP had no effect on length of pediatric intensive care unit stay or duration of mechanical ventilation. The protocol reduced total (5.0 mg/kg [0.5–58.0] vs 4.0 mg/kg [0.0–47.0]; p = 0.021) and daily doses (4.4 mg/kg/d [1.1–33.9] vs 2.9 mg/kg/d [0.0–9.9]; p &lt; 0.001) of benzodiazepines significantly. No difference was observed in total and daily doses of opioids (5.0 mg/kg [0.1–67.0] vs 3.0 mg/kg [0.1–71.0]; p = 0.81) and (0.7 mg/kg/d [0.0–7.0] vs. 0.8 mg/kg/d [0.0–3.7]; p = 0.35), respectively. Rate of withdrawal symptoms was significantly lower after implementation (35.3 vs 20.0%; p = 0.01), but not in patients after solid organ transplantation or oncological patients. Conclusion The nurse-driven analgesia and sedation protocol is an effective procedure to reduce the total doses of benzodiazepines and occurrence of withdrawal symptoms in postsurgical children, which are naïve to opioids or benzodiazepines.
Connectivity map of bipolar cells and photoreceptors in the mouse retina
2016-07-25

Abstract Visual processing begins at the first synapse of the visual system. In the mouse retina, three different types of photoreceptors provide input to 14 bipolar cell (BC) types. Classically, most BC types are thought to contact all cones within their dendritic field; ON BCs would contact cones exclusively via so-called invaginating synapses, while OFF BCs would form basal synapses. By mining publically available electron microscopy data, we discovered interesting violations of these rules of outer retinal connectivity: ON BC type X contacted only ~20% of the cones in its dendritic field and made mostly atypical non-invaginating contacts. Types 5T, 5O and 8 also contacted fewer cones than expected. In addition, we found that rod BCs received input from cones, providing anatomical evidence that rod and cone pathways are interconnected in both directions. This suggests that the organization of the outer plexiform layer is more complex than classically thought.
The LOFT mission concept: a status update
2016-07-25

The Large Observatory For x-ray Timing (LOFT) is a mission concept which was proposed to ESA as M3 and M4 candidate in the framework of the Cosmic Vision 2015-2025 program. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument and the uniquely large field of view of its wide field monitor, LOFT will be able to study the behaviour of matter in extreme conditions such as the strong gravitational field in the innermost regions close to black holes and neutron stars and the supra-nuclear densities in the interiors of neutron stars. The science payload is based on a Large Area Detector (LAD, &gt; 8m(2) effective area, 2-30 keV, 240 eV spectral resolution, 1 degree collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e. g., GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the current technical and programmatic status of the mission.
Returning to the Kamp Mound Group (11C12): Results from Geomagnetic Survey and High-Density Topographic Mapping in Calhoun County, Illinois
2016-07-25

This article addresses the use of high-density topographic mapping and geomagnetic fieldwork as part of an ongoing research program focused on evaluating the role of monumental architecture in the construction and maintenance of differing scales of community during Middle (ca. 50 cal B.C.–cal A.D. 400) and Late (ca. cal A.D. 400–1000) Woodland periods in the Lower Illinois River Valley. At the 2013 Center for American Archeology and Arizona State University field school, a 2.46-ha area at the Kamp Mound Group (11C12) containing Mounds 1, 6, 7, 8, and 9 was surveyed using magnetic fluxgate gradiometry and mapped using a high-density robotic total station. Our survey results demonstrate that highly disturbed mounds have significant interpretable structure that can be used as primary data to better understand spatial attributes related to evaluating site organization, distribution of activity areas in nonmounded space, and internal mound structure and composition.
Convergence of finite elements on a solution-driven evolving surface
2016-07-25

For a parabolic surface partial differential equation coupled to surface evolution, convergence of the spatial semidiscretization is studied in this paper. The velocity of the evolving surface is not given explicitly, but depends on the solution of the parabolic equation on the surface. Various velocity laws are considered: elliptic regularization of a direct pointwise coupling, a regularized mean curvature flow and a dynamic velocity law. A novel stability and convergence analysis for evolving surface finite elements for the coupled problem of surface diffusion and surface evolution is developed. Numerical experiments complement the theoretical results.
The ‘Justinianic Plague’: the economic consequences of the pandemic in the eastern Roman empire and its cultural and religious effects
2016-07-26

Taking as his starting point recent debates over the significance of the ‘Justinianic Plague’ to enquiries into the transition from late antiquity to the early Middle Ages, the author aims to demonstrate that the widely supported relativizing position is untenable. The short‐term demographic and economic consequences of the epidemic must have been catastrophic; the plague, however, seems to have affected the population of the Roman empire in the east most of all in the cultural and religious sphere, in that it prompted or reinforced processes of reorientation that were of fundamental significance to the transformation of the eastern Roman into the Byzantine empire.
Gender and geographical variability in the exposure pattern and metabolism of deoxynivalenol in humans: a review
2016-07-26

Abstract Deoxynivalenol (DON, also known as vomitoxin) is a common mycotoxin found worldwide, especially in contaminated food. DON is toxic to a variety of cells and tissues in humans. Three kinds of conjugated products (DON‐3‐glucuronide, DON‐15‐glucuronide and DON‐7‐glucuronide) can be found as major metabolites in human urine. Females and males show different patterns of exposure levels, and human exposure to DON also shows some geographical differences because of different DON levels in cereal‐based foods, food intake habits and UDP‐glucuronosyltransferase expression. Specifically, the C12, 13‐deepoxy metabolite was found predominantly in French adults but was rarely detected in UK adults. However, a cohort of Spanish individuals demonstrated even lower DON levels than the levels in the UK populations, whereas a very high DON exposure level was detected in South Africa and Linxian, China. Recent publications have further indicated that DON could be detected in the urine of pregnant women from different countries, which suggests that there is a potential risk to both mothers and foetuses. Additionally, phytochemicals have been shown to be less toxic to cells and laboratory animals in research studies and may also be used as food additives for reducing the toxic effects of DON. In this review, we provide global information on DON metabolism, human exposure and gender differences in humans. Also, control strategies for this mycotoxin are discussed. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Trehalose metabolism: A sweet spot for Burkholderia pseudomallei virulence
2016-07-26

peerreview_statement: The publishing and review policy for this title is described in its Aims &amp; Scope.\\naims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&amp;journalCode=kvir20
Blindfolded vs. Informed Ultimatum Bargaining – A Theoretical and Experimental Analysis
2016-07-26

Abstract This paper analyzes blindfolded vs. informed ultimatum bargaining where proposer and responder are both either uninformed or informed about the size of the pie. Considering the transition from one information setting to another suggests that more information induces lower (higher) price offers and acceptance thresholds when the pie is small (large). While our experimental data confirm this transition effect, risk aversion leads to diverging results in blindfolded ultimatum bargaining where task-independent strategies such as ‘equal sharing’ or the ‘golden mean’ are implemented more frequently.
Model-Based Characterization of Inflammatory Gene Expression Patterns of Activated Macrophages
2016-07-27

Macrophages are cells with remarkable plasticity. They integrate signals from their microenvironment leading to context-dependent polarization into classically (M1) or alternatively (M2) activated macrophages, representing two extremes of a broad spectrum of divergent phenotypes. Thereby, macrophages deliver protective and pro-regenerative signals towards injured tissue but, depending on the eliciting damage, may also be responsible for the generation and aggravation of tissue injury. Although incompletely understood, there is emerging evidence that macrophage polarization is critical for these antagonistic roles. To identify activation-specific expression patterns of chemokines and cytokines that may confer these distinct effects a systems biology approach was applied. A comprehensive literature-based Boolean model was developed to describe the M1 (LPS-activated) and M2 (IL-4/13-activated) polarization types. The model was validated using high-throughput transcript expression data from murine bone marrow derived macrophages. By dynamic modeling of gene expression, the chronology of pathway activation and autocrine signaling was estimated. Our results provide a deepened understanding of the physiological balance leading to M1/M2 activation, indicating the relevance of co-regulatory signals at the level of Akt1 or Akt2 that may be important for directing macrophage polarization.
Study of a new central compact object: The neutron star in the supernova remnant G15.9+0.2
2016-07-27

We present our study of the central point source CXOU J181852.0-150213 in the\\nyoung Galactic supernova remnant (SNR) G15.9+0.2 based on the recent ~90 ks\\nChandra observations. The point source was discovered in 2005 in shorter\\nChandra observations and was hypothesized to be a neutron star associated with\\nthe SNR. Our X-ray spectral analysis strongly supports the hypothesis of a\\nthermally emitting neutron star associated with G15.9+0.2. We conclude that the\\nobject belongs to the class of young cooling low-magnetized neutron stars\\nreferred to as central compact objects (CCOs). We modeled the spectrum of the\\nneutron star with a blackbody spectral function and with our hydrogen and\\ncarbon neutron star atmosphere models, assuming that the radiation is uniformly\\nemitted by the entire stellar surface. Under this assumption, only the carbon\\natmosphere models yield a distance that is compatible with a source located in\\nthe Galaxy. In this respect, CXOU J181852.0-150213 is similar to two other\\nwell-studied CCOs, the neutron stars in Cas A and in HESS J1731-347, for which\\ncarbon atmosphere models were used to reconcile their emission with the known\\nor estimated distances.\\n
Giant nerves in chronic inflammatory polyradiculoneuropathy
2016-07-27

ABSTRACT Introduction : Nerve enlargement (NE) is described in inflammatory and inherited neuropathies. It is commonly multifocal and moderate in the former and homogeneous and generalized in the latter. We describe 4 cases of massive NE in inflammatory neuropathies. Methods : Patients presented with symptoms of polyneuropathy that progressed over months to years. Nerve conduction studies (NCS), laboratory analysis, nerve MRI, and nerve ultrasound were performed. Results : NCS revealed demyelinating neuropathy in all with multifocal conduction blocks or increased terminal latency indices. MRI/ultrasound revealed extensive NE in the roots and nerves. Detailed diagnostics including biopsies, positron emission tomography‐computed tomography, and genetic testing revealed no other pathology. Chronic inflammatory demyelinating polyneuropathy variants were diagnosed in all, and immunotherapies were successfully initiated. Conclusions : MRI and ultrasound contributed to diagnosis and therapy. All patients had giant NE in common, which strongly suggested inherited neuropathy. However, the final diagnosis was inflammatory neuropathy. Impressive NE can occur in immune‐mediated neuropathies and should be carefully differentiated from inherited neuropathies. Muscle Nerve 55 : 285–289, 2017
Multimodal Assessment Reveals Late-Onset Hemispheric Shift of Language in a Child with Meningocerebral Dysplasia
2016-07-27

We report on a girl with progressive left frontal tissue destruction starting at the age of almost 8 years. She manifested acutely with epileptic seizures accompanied by Broca aphasia as well as transient right hemiparesis. Due to refractory epilepsy developing over the next years, which originated from the left frontal lobe, the decision was made to proceed to epilepsy surgery. By then, her language functions had recovered despite progressive left frontal tissue-destruction, raising the possibility of a hemispheric shift of language. Clinical functional magnetic resonance imaging (fMRI) was conducted to localize brain regions involved in language production. A complex pattern of clear right-hemispheric dominance, but with some left-sided contribution was found. However, a Wada test suggested the left hemisphere to be critical, seemingly contradicting fMRI. Invasive electroencephalogram recordings could reconcile these results by identifying the fMRI-detected, residual left-sided activation as being relevant for speech production. Only by combining the localizing information from fMRI with the information obtained by two invasive procedures could the unusual pattern of late-onset language reorganization be uncovered. This allowed for extensive left frontal resection, with histology confirming meningocerebral angiodysplasia. Postoperatively, language functions were preserved and seizure outcome was excellent. The implications of our findings for presurgical assessments in children are discussed.
Detection of the plant parasite Cuscuta reflexa by a tomato cell surface receptor
2016-07-28

Resistance is not, after all, futile The parasitic plant known as dodder attaches to its hosts and sucks the life out of them. Oddly, the common tomato stands tall when under attack. Hegenauer et al. have leveraged that difference to identify part of the molecular defense system that protects tomato plants (see the Perspective by Ntoukakis and Gimenez-Ibanez). In a process analogous to defenses mounted against microbial infection, the host plant perceives a small-peptide signal from the parasitic plant and initiates defense responses. The candidate receptor isolated from the tomato plant provided partial protection when transferred to two other susceptible plant species. Science , this issue p. 478 ; see also p. 442
Lung Cancer: EGFR Inhibitors with Low Nanomolar Activity against a Therapy‐Resistant L858R/T790M/C797S Mutant
2016-07-28

Abstract The treatment of non‐small‐cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors is made challenging by acquired resistance caused by somatic mutations. Third‐generation EGFR inhibitors have been designed to overcome resistance through covalent binding to the Cys 797 residue of the enzyme, and these inhibitors are effective against most clinically relevant EGFR mutants. However, the high dependence of these recent EGFR inhibitors on this particular interaction means that additional mutation of Cys 797 results in poor inhibitory activity, which leads to tumor relapse in initially responding patients. A new generation of irreversible and reversible mutant EGFR inhibitors was developed with strong noncovalent binding properties, and these compounds show high inhibitory activities against the cysteine‐mutated L858R/T790M/C797S EGFR.