julilili42/papers huggingface dataset:
Revisiting the divide between deontology and utilitarianism in moral dilemma judgment: A multinomial modeling approach.
2019-09-03

We investigate the psychological bases underlying moral dilemma judgment with the help of multinomial processing tree modeling, and consider how determinants of dilemma judgment should best be conceptualized. We argue that, for conceptual as well as empirical reasons, norms and consequences should be considered as more intimately linked with one another than their systematic juxtaposition in dilemma research may suggest, and propose that norm-endorsement should be viewed through a consequentialist lens as well. Investigating this proposal, we introduce a variant of the CNI model of moral dilemma judgment, which focuses on the use of proscriptive norms only. In five experiments, we validate this proCNI model and assess the parameters' sensitivity to different types of consequences and personal involvement. Our findings suggest that the parameter representing "norms" is sensitive to consequences as well, such that norms do not guide moral judgment unless they are expected to produce tangible consequences. Thus, present research suggests that the split between norms and "consequences" (or "deontology" and "utilitarianism") as determinants of judgment is artificial. We suggest that, ultimately, viewing dilemma judgments through a consequentialist lens may be a useful approach for advancing theoretical development in the field of dilemma research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Molecular basis for functional diversity among microbial Nep1-like proteins
2019-09-03

Necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are secreted by several phytopathogenic microorganisms. They trigger necrosis in various eudicot plants upon binding to plant sphingolipid glycosylinositol phosphorylceramides (GIPC). Interestingly, HaNLP3 from the obligate biotroph oomycete Hyaloperonospora arabidopsidis does not induce necrosis. We determined the crystal structure of HaNLP3 and showed that it adopts the NLP fold. However, the conformations of the loops surrounding the GIPC headgroup-binding cavity differ from those of cytotoxic Pythium aphanidermatum NLPPya. Essential dynamics extracted from μs-long molecular dynamics (MD) simulations reveals a limited conformational plasticity of the GIPC-binding cavity in HaNLP3 relative to toxic NLPs. This likely precludes HaNLP3 binding to GIPCs, which is the underlying reason for the lack of toxicity. This study reveals that mutations at key protein regions cause a switch between non-toxic and toxic phenotypes within the same protein scaffold. Altogether, these data provide evidence that protein flexibility is a distinguishing trait of toxic NLPs and highlight structural determinants for a potential functional diversification of non-toxic NLPs utilized by biotrophic plant pathogens.
Current time-temperature relationships for thermal inactivation of Ascaris eggs at mesophilic temperatures are too conservative and may hamper development of simple, but effective sanitation
2019-09-03

<i>Ascaris</i> eggs are commonly used as indicators for pathogen inactivation during the treatment of fecal sludge and wastewater due to their highly resistant lipid membrane and ability to survive in the environment for long periods of time. Current guidelines suggest that thermal treatment alone cannot inactivate <i>Ascaris</i> eggs at temperatures below 45 °C, although some evidence in the literature suggests this to be incorrect. Here, we performed a controlled experiment to test the effect of mesophilic temperatures on <i>Ascaris</i> inactivation. We exposed <i>Ascaris suum</i> eggs to a temperature gradient between 34°C and 45 °C under anaerobic and aerobic conditions to observe the required exposure times for a 3-log reduction. Indeed, we found that temperatures lower than 45 °C did inactivate these eggs, and the required exposure times were up to two orders of magnitude shorter than suggested by current guidelines. Results from the anaerobic exposures were used to develop a time-temperature relationship that is appropriate for <i>Ascaris</i> inactivation at mesophilic temperatures. Data from the literature demonstrated that our relationship is conservative, with faster inactivation occurring under environmental conditions when <i>Ascaris</i> eggs were suspended in fecal sludge or manure. A specific aerobic relationship was not developed, but we demonstrated that aerobic conditions cause faster inactivation than anaerobic conditions. Therefore, the anaerobic relationship provides a conservative guideline for both conditions. We demonstrate that relatively low temperatures can considerably impact <i>Ascaris</i> viability and suggest that mesophilic temperatures can be used in waste treatment processes to inactivate pathogens. The development of safe, low-input, mesophilic treatment processes is particularly valuable for ensuring universal access to safe sanitation and excreta management.
The Tyrosine-Autokinase UbK Is Required for Proper Cell Growth and Cell Morphology of Streptococcus pneumoniae
2019-09-03

Protein phosphorylation is a key post-translational modification required for many cellular functions of the bacterial cell. Recently, we identified a new protein-kinase, named UbK, in <i>Bacillus subtilis</i> that belongs to a new family of protein-kinases widespread in bacteria. In this study, we analyze the function of UbK in <i>Streptococcus pneumoniae</i>. We show that UbK displays a tyrosine-kinase activity and autophosphorylates on a unique tyrosine <i>in vivo</i>. To get insights into its cellular role, we constructed a set of pneumococcal <i>ubk</i> mutants. Using conventional and electron microscopy, we show that the <i>ubk</i> deficient strain, as well as an <i>ubk</i> catalytic dead mutant, display both severe cell-growth and cell-morphology defects. The same defects are observed with a mutant mimicking permanent phosphorylation of UbK whereas they are not detected for a mutant mimicking defective autophosphorylation of UbK. Moreover, we find that UbK phosphorylation promotes its ability to hydrolyze ATP. These observations show that the hydrolysis of ATP by UbK serves not only for its autophosphorylation but also for a distinct purpose essential for the optimal cell growth and cell-morphogenesis of the pneumococcus. We thus propose a model in which the autophosphorylation/dephosphorylation of UbK regulates its cellular function through a negative feedback loop.
The Pikermian tortoises (Testudines, Testudinidae) from the late Miocene of the South Balkans
2019-09-03

This article deals with the fossil tortoises of one of the most iconic fossil localities of the Neogene of the Old World, the upper Miocene locality of Pikermi, near Athens, Greece. We describe the type, previously published, and new material of the fossil tortoises from Pikermi, along with new material from the coeval Azmaka 6 locality in Bulgaria. This combined information results in the complete revision of the 'marble tortoise' Testudo marmorum, which is the first turtle species ever named from Greece. Besides the challenges and difficulties of working with material from the old collections of Pikermi, we present a complete revision of this species and identify its presence outside its type locality in the South Balkan Peninsula. The presence of numerous shells of the 'marble tortoise' allows us to discuss the observed variation and attempt to interpret it as the result of intraspecific variation, ontogenetic changes, or sexual dimorphism. For the first time, we observe the absence of the characteristic hypo-xiphiplastral hinge in female individuals of Testudo marmorum, which in turn challenges the traditional phylogenetic position of this species. We further describe previously published and new material of the giant tortoise Titanochelon from Pikermi. Based on the updated information, we can suggest that the Pikermian giant tortoise probably represents a distinct taxon. Our results signal Pikermi as one of the most important localities to understand the evolution of tortoises in the eastern Mediterranean during the last parts of the Neogene.
Temporal Dynamics of Reactive Oxygen and Nitrogen Species and NF-κB Activation During Acute and Chronic T Cell–Driven Inflammation
2019-09-03

Noninvasive in vivo imaging is capable of assessing the temporal dynamics of ROS/RNS production and NF-κB activation during progression from acute to chronic DTHR and enables monitoring of anti-inflammatory treatment responses.
Type-specific dendritic integration in mouse retinal ganglion cells
2019-09-03

ABSTRACT Neural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, the fundamental rules that govern dendritic integration are far from understood. In particular, it is still unclear how cell type-specific differences in dendritic integration arise from general features of neural morphology and membrane properties. Here, retinal ganglion cells (RGCs), which relay the visual system’s first computations to the brain, represent an exquisite model. They are functionally and morphologically diverse yet defined, and they allow studying dendritic integration in a functionally relevant context. Here, we show how four morphologically distinct types of mouse RGC with shared excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-mini Off ) exhibit distinct dendritic integration rules. Using two-photon imaging of dendritic calcium signals and biophysical modelling, we demonstrate that these RGC types strongly differ in their spatio-temporal dendritic integration: In transient Off alpha cells, dendritic receptive fields displayed little spatial overlap, indicative of a dendritic arbour that is partitioned in largely isolated regions. In contrast, dendritic receptive fields in the other three RGCs overlapped greatly and were offset to the soma, suggesting strong synchronization of dendritic signals likely due to backpropagation of somatic signals. Also temporal correlation of dendritic signals varied extensively among these types, with transient Off mini cells displaying the highest correlation across their dendritic arbour. Modelling suggests that morphology alone cannot explain these differences in dendritic integration, but instead specific combinations of dendritic morphology and ion channel densities are required. Together, our results reveal how neurons exhibit distinct dendritic integration profiles tuned towards their type-specific computations in their circuits, with the interplay between morphology and ion channel complement as a key contributor.
Nanoscale Photovoltaic Responses in 3D Radial Junction Solar Cells Revealed by High Spatial Resolution Laser Excitation Photoelectric Microscopy
2019-09-03

The actual light absorption photovoltaic responses realized in three-dimensional (3D) radial junction (RJ) units can be rather different from their planar counterparts and remain largely unexplored. We here adopt a laser excitation photoelectric microscope (LEPM) technology to probe the local light harvesting and photoelectric signals of 3D hydrogenated amorphous silicon (a-Si:H) RJ thin film solar cells constructed over a Si nanowire (SiNW) matrix, with a high spatial resolution of 600 nm thanks to the use of a high numerical aperture objective. The LEPM scan can help to resolve clearly the impacts of local structural damages, which are invisible to optical and SEM observations. More importantly, the high-resolution photoelectric mapping establishes a straightforward link between the local 3D geometry of RJ units and their light conversion performance. Surprisingly, it is found that the maximal photoelectric signals are usually recorded in the void locations among the standing SiNW RJs, instead of the overhead positions above the RJs. This phenomenon can be well explained and reproduced by finite element simulation analysis, which highlights unambiguously the dominant contribution of inter-RJ-unit scattering against direct mode incoupling in the 3D solar cell architecture. This LEPM mapping technology and the results help to achieve a straightforward and high-resolution evaluation of the local photovoltaic responses among the 3D RJ units, providing a solid basis for further structural optimization and performance improvement.
Small vertebrates from the upper Miocene hominoid-bearing site of Udabno, Georgia
2019-09-03

The locality of Udabno, Georgia, preserves material referred to the hominoid primate Dryopithecus. In this study, we describe the microvertebrate fauna from the site, which includes fishes (Scardinius sp., Carassius sp.), anurans (Pelophylax sp.), squamates (Lacertidae indet., Ophidia indet.), insectivores (Schizogalerix sinapensis, Turiasorex cf. pierremeini), and rodents (Byzantinia pikermiensis, Hansdebruijnia erksinae, Vasseuromys pannonicus). The association of two rodents, the cricetid B. pikermiensis and the murid H. erksinae, constrains the age of the Udabno fauna more precisely than previous studies. Byzantinia pikermiensis was first recognized at the site of Pikermi, Chomateri, and later recovered in other sites from Turkey, including the hominid-bearing site of Çorakyerler. The murid H. erksinae was also described from Çorakyerler in Turkey. Therefore, the presence of these rodents at Udabno indicates that the fauna postdates late Vallesian faunas such as Biodrak, Greece, and Bayraktepe II, Turkey, which are characterized by the association of the more archaic species Byzantinia nikosi and Progonomys cathalai. This study demonstrates that Udabno is temporally equivalent to typical Turolian sites from the Mediterranean area, such as Pikermi, Çorakyerler, and Crevillente 2.
PD-1 and LAG-3 Dominate Checkpoint Receptor–Mediated T-cell Inhibition in Renal Cell Carcinoma
2019-09-04

Abstract Drugs targeting the programmed cell death protein 1 (PD-1) pathway are approved as therapies for an increasing number of cancer entities, including renal cell carcinoma. Despite a significant increase in overall survival, most treated patients do not show durable clinical responses. A combination of checkpoint inhibitors could provide a promising improvement. The aim of the study was to determine the most promising checkpoint blockade combination for renal cell carcinoma patients. Tumor-infiltrating lymphocytes (TIL) and autologous peripheral blood mononuclear cells (PBMC) were isolated from patients undergoing surgery for primary tumors. Cells were stained for multicolor flow cytometry to determine the (co)expression of five inhibitory receptors (iR), PD-1, LAG-3, Tim-3, BTLA, and CTLA-4, on T-cell populations. The function of these TILs was assessed by intracellular cytokine staining after in vitro stimulation in the presence or absence of PD-1 ± LAG-3 or Tim-3–specific antibodies. Although the percentage of iR+ T cells was low in PBMCs, both CD4+ and CD8+ T cells showed increased frequencies of PD-1+, LAG-3+, and Tim-3+ cells on TILs. The most frequent iR combination was PD-1 and LAG-3 on both CD4+ and CD8+ TILs. Blockade of PD-1 resulted in significant LAG-3, but not Tim-3, upregulation. The dual blockade of PD-1 and LAG-3, but not PD-1 and Tim-3, led to increased IFNγ release upon in vitro stimulation. Together, these data suggest that dual blockade of PD-1 and LAG-3 is a promising checkpoint blockade combination for renal cell carcinoma.
The effects of working memory and declarative memory on instructed second language vocabulary learning: Insights from intelligent CALL
2019-09-04

The extent to which learners benefit from instruction may be largely dependent on their individual abilities. However, there is relatively little work on the interaction between instructional effectiveness in second language learning and learner individual factors. In this study, we investigated the relationship between instruction, individual differences in cognitive abilities (working memory and declarative memory), and second language vocabulary acquisition in the context of web-based intelligent computer assisted language learning (ICALL). To this end, 127 adult learners of English, predominantly advanced-level, German-speaking learners, read news texts on the web for about two weeks using an ICALL system under two instructional conditions: form-focused and meaning-focused instruction. Learners in the form-focused condition read and completed automatically-generated multiple-choice gaps where phrasal verbs appeared in the text, while learners in the meaning-focused condition simply read and did not complete any gaps. Mixed-effects regression analyses showed that working memory was associated with vocabulary acquisition and that this association depended on the instructional context, with working memory being predictive of learning only in the form-focused condition, suggesting an aptitude-treatment interaction. Furthermore, declarative memory abilities were related to learning only as measured by the Continuous Visual Memory Task, and the relationship was not moderated by instructional condition. Overall, the study contributes to accounting for variability in second language learning in general, as well as in instructional contexts supported by intelligent CALL.
A 32‐channel multi‐coil setup optimized for human brain shimming at 9.4T
2019-09-04

Purpose A multi‐coil shim setup is designed and optimized for human brain shimming. Here, the size and position of a set of square coils are optimized to improve the shim performance without increasing the number of local coils. Utilizing such a setup is especially beneficial at ultrahigh fields where B 0 inhomogeneity in the human brain is more severe. Methods The optimization started with a symmetric arrangement of 32 independent coils. Three parameters per coil were optimized in parallel, including angular and axial positions on a cylinder surface and size of the coil, which were constrained by cylinder size, construction consideration, and amplifiers specifications. B 0 maps were acquired at 9.4T in 8 healthy volunteers for use as training data. The global and dynamic shimming performance of the optimized multi‐coil were compared in simulations and measurements to a symmetric design and to the scanner's second‐order shim setup, respectively. Results The optimized multi‐coil performs better by 14.7% based on standard deviation (SD) improvement with constrained global shimming in comparison to the symmetric positioning of the coils. Global shimming performance was comparable with a symmetric 65‐channel multi‐coil and full fifth‐order spherical harmonic shim coils. On average, an SD of 48.4 and 31.9 Hz was achieved for in vivo measurements after global and dynamic slice‐wise shimming, respectively. Conclusions An optimized multi‐coil shim setup was designed and constructed for human whole‐brain shimming. Similar performance of the multi‐coils with many channels can be achieved with a fewer number of channels when the coils are optimally arranged around the target.
Association between depression subtypes and response to repeated‐dose intravenous ketamine
2019-09-04

Objective About half or more of treatment‐resistant depressed patients do not respond to ketamine, and few clinical predictors to gauge the most likely antidepressant response have been proposed. We explored whether depression subtypes are associated with response to ketamine. Method Ninety‐seven participants with depression were administered six repeated‐dose intravenous ketamine and assessed for depression (Montgomery–Åsberg Depression Rating Scale, MADRS ), anxiety (Hamilton Anxiety Rating Scale, HAMA ), and suicidal ideation (Beck Scale for Suicidal Ideation, SSI ) at baseline, 24 h after each infusion, and 2 weeks after the whole treatment. Participants were classified by melancholic/anxious subtype. Individuals who met criteria for neither or both subtypes were classified separately, resulting in four mutually exclusive groups. Results Patients with melancholic or melancholic–anxious features were less likely to respond (e.g., day 13, melancholic–anxious vs. anxious, OR 0.138, 95% CI 0.032–0.584, P = 0.007) or remit (e.g., day 26, melancholic vs. no subtype, OR 0.182, 95% CI 0.035–0.960, P = 0.045) and took longer to achieve response/remission than those with anxious or no subtype features. Faster HAMA score reductions were observed in patients with anxious or melancholic–anxious features, and faster SSI score reductions were observed among those with melancholic–anxious features. Conclusion Our study shows promising results for ketamine as a novel antidepressant preferentially for the treatment of non‐melancholic or anxious depression.
The mitochondrial intermembrane space–facing proteins Mcp2 and Tgl2 are involved in yeast lipid metabolism
2019-09-04

Mitochondria are unique organelles harboring two distinct membranes, the mitochondrial inner and outer membrane (MIM and MOM, respectively). Mitochondria comprise only a subset of metabolic pathways for the synthesis of membrane lipids; therefore most lipid species and their precursors have to be imported from other cellular compartments. One such import process is mediated by the ER mitochondria encounter structure (ERMES) complex. Both mitochondrial membranes surround the hydrophilic intermembrane space (IMS). Therefore, additional systems are required that shuttle lipids between the MIM and MOM. Recently, we identified the IMS protein Mcp2 as a high-copy suppressor for cells that lack a functional ERMES complex. To understand better how mitochondria facilitate transport and biogenesis of lipids, we searched for genetic interactions of this suppressor. We found that MCP2 has a negative genetic interaction with the gene TGL2 encoding a neutral lipid hydrolase. We show that this lipase is located in the intermembrane space of the mitochondrion and is imported via the Mia40 disulfide relay system. Furthermore, we show a positive genetic interaction of double deletion of MCP2 and PSD1, the gene encoding the enzyme that synthesizes the major amount of cellular phosphatidylethanolamine. Finally, we demonstrate that the nucleotide-binding motifs of the predicted atypical kinase Mcp2 are required for its proper function. Taken together, our data suggest that Mcp2 is involved in mitochondrial lipid metabolism and an increase of this involvement by overexpression suppresses loss of ERMES.