bluuebunny/crossref_metadata_2025 huggingface dataset:
Subdural Instillation of a Thrombolytic Agent for Treatment of Recurrent Subdural Hematoma
Authors: Frenkel Mark B. , Sarwal Aarti , Wren Mary Petrulis , Newey Christopher R. , Couture Daniel E.
Published: October 2017

Objective

This study aims to report the case of a patient with recurrent subdural hemorrhage (SDH) who was administered tissue plasminogen activator through a subdural drain to enhance drainage and prevent recurrence.

Methods

An 85-year-old man was treated for subacute over chronic SDH that kept on reaccumulating despite serial twist drill drainage, burr hole drainage, and craniotomy. No coagulopathy was identified with adequate blood pressure control.

Results

Treatment with tissue plasminogen activator resulted in successful drainage of the SDH, and the patient had no further recurrence at 9-month follow-up.
Early Onset Schizophrenia Associated With Obsessive-Compulsive Disorder: Clinical Features and Correlates
Authors: Baytunca Burak , Kalyoncu Tuğba , Ozel Ismail , Erermiş Serpil , Kayahan Bülent , Öngur Dost
Published: October 2017

Objectives

Obsessive-compulsive disorder (OCD) is notably a comorbid disorder in patients with schizophrenia. This study aimed to evaluate clinical features and correlates of early onset patients with schizophrenia with OCD.

Methods

In the present study, we included 10 patients with both schizophrenia and OCD and 19 patients with schizophrenia without OCD. The mean antipsychotic doses the patients needed for treatment are standardized as chlorpromazine equivalent dose.

Results

The mean antipsychotic doses at first episode were 491 ± 376 mg/d in schizophrenia comorbid OCD group and 290 ± 209 mg/d in the schizophrenia without OCD group (P = 0.018). This significant difference was also found for the mean doses at the assessment for the study (512.40 ± 336.22 mg/d in schizophrenia comorbid OCD and 296.05 ± 147.25 mg/d in patients with schizophrenia without OCD, P = 0.012). There was no statistical difference in the mean scores of Clinical Global Impression and Positive and Negative Syndrome Scale between schizophrenia with and without OCD group, respectively. (Clinical Global Impression: 5 ± 0.66 vs 4.36 ± 0.83, P = 0.094; Positive and Negative Syndrome Scale: 67.60 ± 11.84 vs 69.84 ± 14.62, P = 0.573).

Conclusions

Adolescents with schizophrenia and OCD needed more antipsychotic doses for acute exacerbation and the maintenance of reduction of psychosis severity than adolescents with only schizophrenia. We could suggest that OCD comorbidity in schizophrenia is more treatment resistant, although the severity of the schizophrenia was similar between study groups. There was no correlation between OCD and schizophrenia symptoms either.
Validation of the 10-Item Orientation Questionnaire
Authors: Martin Donel M. , Wong Ada , Kumar Divya R. , Loo Colleen K.
Published: October 2017

Objectives

Assessment of post–electroconvulsive therapy (ECT) disorientation at a single time point after ECT treatment may prove an effective and clinically useful method for monitoring the severity of disorientation and predicting ECT-induced retrograde amnesia. In this study, we aimed to validate a novel instrument (10-Item Orientation Questionnaire) developed to assess the level of disorientation after ECT.

Methods

Twenty-four depressed inpatients who were prescribed an acute course of ECT were administered the 10-Item Orientation Questionnaire at 30 minutes after ECT and had time to reorientation assessed at 3 time points after ECT (10, 30, and 60 minutes) at ECT treatments 1 to 3. The association between average performance of the 10-Item Orientation Questionnaire across the acute ECT course and retrograde amnesia at post-ECT was examined using the Autobiographical Memory Interview–Short Form.

Results

Mean performance on the 10-Item Orientation Questionnaire across treatments 1 to 3 was moderately correlated with average time to reorientation (r= −0.52,P= 0.02, n = 20). Across the acute ECT course, poorer performance on the 10-Item Orientation Questionnaire was associated with greater retrograde amnesia at post-ECT (r= 0.53,P= 0.03, n = 16).

Conclusions

The 10-Item Orientation Questionnaire when administered at 30 minutes after ECT is sensitive for detecting patients with slow recovery of orientation after ECT. Use of this instrument therefore has potential for improving routine patient monitoring in clinical practice and identifying patients at increased risk of retrograde memory adverse effects following treatment.
A complete characterization of all-versus-nothing arguments for stabilizer states
Authors: Abramsky Samson , Barbosa Rui Soares , Carù Giovanni , Perdrix Simon
Published: October 2017

An important class of contextuality arguments in quantum foundations are the all-versus-nothing (AvN) proofs, generalizing a construction originally due to Mermin. We present a general formulation of AvN arguments and a complete characterization of all such arguments that arise from stabilizer states. We show that every AvN argument for an
n
-qubit stabilizer state can be reduced to an AvN proof for a three-qubit state that is local Clifford-equivalent to the tripartite Greenberger–Horne–Zeilinger state. This is achieved through a combinatorial characterization of AvN arguments, the AvN triple theorem, whose proof makes use of the theory of graph states. This result enables the development of a computational method to generate all the AvN arguments in

on
n
-qubit stabilizer states. We also present new insights into the stabilizer formalism and its connections with logic.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Dynamics of quantum measurements employing two Curie–Weiss apparatuses
Authors: Perarnau-Llobet Martí , Nieuwenhuizen Theodorus Maria
Published: October 2017

Two types of quantum measurements, measuring the spins of an entangled pair and attempting to measure a spin at either of two positions, are analysed dynamically by apparatuses of the Curie–Weiss type. The outcomes comply with the standard postulates.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
The Higgs field and the resolution of the Cosmological Constant Paradox in the Weyl-geometrical Universe
Authors: De Martini Francesco
Published: October 2017

The nature of the scalar field responsible for the cosmological inflation is found to be rooted in the most fundamental concept of Weyl's differential geometry: the parallel displacement of vectors in curved space–time. Within this novel geometrical scenario, the standard electroweak theory of leptons based on theSU(2)L⊗U(1)Yas well as on the conformal groups of space–time Weyl's transformations is analysed within the framework of a general-relativistic, conformally covariant scalar-tensor theory that includes the electromagnetic and the Yang–Mills fields. A Higgs mechanism within a spontaneous symmetry breaking process is identified and this offers formal connections between some relevant properties of the elementary particles and the dark energy content of the Universe. An ‘effective cosmological potential’:Veffis expressed in terms of the dark energy potential:via the ‘mass reduction parameter’:, a general property of the Universe. The mass of the Higgs boson, which is considered a ‘free parameter’ by the standard electroweak theory, by our theory is found to be proportional to the masswhich accounts for the measured cosmological constant, i.e. the measured content of vacuum-energy in the Universe. The non-integrable application of Weyl's geometry leads to a Proca equation accounting for the dynamics of aϕρ-particle, a vector-meson proposed as an an optimum candidate for dark matter. On the basis of previous cosmic microwave background results our theory leads, in the condition of cosmological ‘critical density’, to the assessment of the average energy content of theϕρ-excitation. The peculiar mathematical structure ofVeffoffers a clue towards a very general resolution of a most intriguing puzzle of modern quantum field theory, the ‘Cosmological Constant Paradox’ (here referred to as the ‘Λ-Paradox’). Indeed, our ‘universal’ theory offers a resolution of theΛ-Paradox for all exponential inflationary potentials:VΛ(T,ϕ)∝e−nϕ, and for all linear superpositions of these potentials, wherenbelongs to the mathematical set of the ‘real numbers’. An explicit solution of theΛ-Paradox is reported forn=2. The resolution of theΛ-Paradox cannot be achieved in the context of Riemann's differential geometry.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Quantum potentiality revisited
Authors: Jaeger Gregg
Published: October 2017

Heisenberg offered an interpretation of the quantum state which made use of a quantitative version of an earlier notion,, of Aristotle by both referring to it using its Latin name,potentia, and identifying its qualitative aspect with. The relationship between this use and Aristotle's notion was not made by Heisenberg in full detail, beyond noting their common character: that of signifying the system's objective capacity to be found later to possess a property in actuality. For such actualization, Heisenberg requiredmeasurementto have taken place, an interaction with external systems that disrupts the otherwise independent, natural evolution of the quantum system. The notion of state actualization was later taken up by others, including Shimony, in the search for a law-like measurement process. Yet, the relation of quantum potentiality to Aristotle's original notion has been viewed as mainly terminological, even by those who used it thus. Here, I reconsider the relation of Heisenberg's notion to Aristotle's and show that it can be explicated in greater specificity than Heisenberg did. This is accomplished through the careful consideration of the role of potentia in physical causation and explanation, and done in order to provide a fuller understanding of this aspect of Heisenberg's approach to quantum mechanics. Most importantly, it is pointed out that Heisenberg's requirement of an external intervention during measurement that disrupts the otherwise independent, natural evolution of the quantum system is in accord with Aristotle's characterization of spontaneous causation. Thus, the need for a teleological understanding of the actualization of potentia, an often assumed requirement that has left this fundamental notion neglected, is seen to be spurious.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Quantum generalized observables framework for psychological data: a case of preference reversals in US elections
Authors: Khrennikova Polina , Haven Emmanuel
Published: October 2017

Politics is regarded as a vital area of public choice theory, and it is strongly relying on the assumptions of voters’ rationality and as such, stability of preferences. However, recent opinion polls and real election outcomes in the USA have shown that voters often engage in ‘ticket splitting’, by exhibiting contrasting party support in Congressional and Presidential elections (cf. Khrennikova 2014Phys. ScriptaT163, 014010 (doi:10.1088/0031-8949/2014/T163/014010); Khrennikova & Haven 2016Phil. Trans. R. Soc. A374, 20150106 (doi:10.1098/rsta.2015.0106); Smithet al.1999Am. J. Polit. Sci.43, 737–764 (doi:10.2307/2991833)). Such types of preference reversals cannot be mathematically captured via the formula of total probability, thus showing that voters’ decision making is at variance with the classical probabilistic information processing framework. In recent work, we have shown that quantum probability describes well the violation of Bayesian rationality in statistical data of voting in US elections, through the so-calledinterference effectsof probability amplitudes. This paper is proposing a novel generalized observables framework of voting behaviour, by using the statistical data collected and analysed in previous studies by Khrennikova (Khrennikova 2015Lect. Notes Comput. Sci.8951, 196–209) and Khrennikova & Haven (Khrennikova & Haven 2016Phil. Trans. R. Soc. A374, 20150106 (doi:10.1098/rsta.2015.0106)). This framework aims to overcome the main problems associated with the quantum probabilistic representation of psychological data, namely thenon-double stochasticityof transition probability matrices. We develop a simplified construction of generalized positive operator valued measures by formulating special non-orthonormal bases with respect to these operators.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Can we close the Bohr–Einstein quantum debate?
Authors: Kupczynski Marian
Published: October 2017

Recent experiments allow one to conclude that Bell-type inequalities are indeed violated; thus, it is important to understand what this means and how we can explain the existence of strong correlations between outcomes of distant measurements. Do we have to announce that Einstein was wrong, Nature is non-local and non-local correlations are produced due to quantum magic and emerge, somehow, from outside space–time? Fortunately, such conclusions are unfounded because, if supplementary parameters describing measuring instruments are correctly incorporated in a theoretical model, then Bell-type inequalities may not be proved. We construct a simple probabilistic model allowing these correlations to be explained in a locally causal way. In our model, measurement outcomes are neither predetermined nor produced in an irreducibly random way. We explain why, contrary to the general belief, the introduction of setting-dependent parameters does not restrict experimenters' freedom of choice. Since the violation of Bell-type inequalities does not allow the conclusion that Nature is non-local and that quantum theory is complete, the Bohr–Einstein quantum debate may not be closed. The continuation of this debate is important not only for a better understanding of Nature but also for various practical applications of quantum phenomena.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Quantum mechanics: why complex Hilbert space?
Authors: Cassinelli G. , Lahti P.
Published: October 2017

We outline a programme for an axiomatic reconstruction of quantum mechanics based on the statistical duality of states and effects that combines the use of a theorem of Solér with the idea of symmetry. We also discuss arguments favouring the choice of the complex field.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Quantum Bayesian perspective for intelligence reservoir characterization, monitoring and management
Authors: Lozada Aguilar Miguel Ángel , Khrennikov Andrei , Oleschko Klaudia , de Jesús Correa María
Published: October 2017

The paper starts with a brief review of the literature about uncertainty in geological, geophysical and petrophysical data. In particular, we present the viewpoints of experts in geophysics on the application of Bayesian inference and subjective probability. Then we present arguments that the use of classical probability theory (CP) does not match completely the structure of geophysical data. We emphasize that such data are characterized by contextuality and non-Kolmogorovness (the impossibility to use the CP model), incompleteness as well as incompatibility of some geophysical measurements. These characteristics of geophysical data are similar to the characteristics of quantum physical data. Notwithstanding all this, contextuality can be seen as a major deviation of quantum theory from classical physics. In particular, the contextual probability viewpoint is the essence of the Växjö interpretation of quantum mechanics. We propose to use quantum probability (QP) for decision-making during the characterization, modelling, exploring and management of theintelligent hydrocarbon reservoir. Quantum Bayesianism (QBism), one of the recently developed information interpretations of quantum theory, can be used as the interpretational basis for such QP decision-making in geology, geophysics and petroleum projects design and management.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
A model of adaptive decision-making from representation of information environment by quantum fields
Authors: Bagarello F. , Haven E. , Khrennikov A.
Published: October 2017

We present the mathematical model of decision-making (DM) of agents acting in a complex and uncertain environment (combining huge variety of economical, financial, behavioural and geopolitical factors). To describe interaction of agents with it, we apply the formalism of quantum field theory (QTF). Quantum fields are a purely informational nature. The QFT model can be treated as a far relative of the expected utility theory, where the role of utility is played by adaptivity to an environment (bath). However, this sort of utility–adaptivity cannot be represented simply as a numerical function. The operator representation in Hilbert space is used and adaptivity is described as in quantum dynamics. We are especially interested in stabilization of solutions for sufficiently large time. The outputs of this stabilization process, probabilities for possible choices, are treated in the framework of classical DM. To connect classical and quantum DM, we appeal to Quantum Bayesianism. We demonstrate the quantum-like interference effect in DM, which is exhibited as a violation of the formula of total probability, and hence the classical Bayesian inference scheme.

This article is part of the themed issue ‘Second quantum revolution: foundational questions’.
Patchy promiscuity: machine learning applied to predict the host specificity of Salmonella enterica and Escherichia coli
Authors: Lupolova Nadejda , Dallman Tim J. , Holden Nicola J. , Gally David L.
Published: October 2017

Salmonella enterica and Escherichia coli are bacterial species that colonize different animal hosts with sub-types that can cause life-threatening infections in humans. Source attribution of zoonoses is an important goal for infection control as is identification of isolates in reservoir hosts that represent a threat to human health. In this study, host specificity and zoonotic potential were predicted using machine learning in which Support Vector Machine (SVM) classifiers were built based on predicted proteins from whole genome sequences. Analysis of over 1000 S.
enterica genomes allowed the correct prediction (67 –90 % accuracy) of the source host for S. Typhimurium isolates and the same classifier could then differentiate the source host for alternative serovars such as S. Dublin. A key finding from both phylogeny and SVM methods was that the majority of isolates were assigned to host-specific sub-clusters and had high host-specific SVM scores. Moreover, only a minor subset of isolates had high probability scores for multiple hosts, indicating generalists with genetic content that may facilitate transition between hosts. The same approach correctly identified human versus bovine E. coli isolates (83 % accuracy) and the potential of the classifier to predict a zoonotic threat was demonstrated using E. coli O157. This research indicates marked host restriction for both S. enterica and E. coli, with only limited isolate subsets exhibiting host promiscuity by gene content. Machine learning can be successfully applied to interrogate source attribution of bacterial isolates and has the capacity to predict zoonotic potential.
Novel Compensatory Mechanisms Enable the Mutant KCNT1 Channels to Induce Seizures
Authors: Ehaideb Salleh N. , Decker Gentry T. , Smith Petrina , Davis Daniel , Zhang Bing
Published: October 2017

Mutations in the sodium-activated potassium channel (KCNT1) gene are linked to epilepsy. Surprisingly, all KCNT1 mutations examined to date increase K+current amplitude. These findings present a major neurophysiological paradox: how do gain-of-function KCNT1 mutations expected to silence neurons cause epilepsy? Here, we useDrosophilato show that expressing mutant KCNT1 in GABAergic neurons leads to seizures, consistent with the notion that silencing inhibitory neurons tips the balance towards hyperexcitation. Unexpectedly, mutant KCNT1 expressed in motoneurons also causes seizures. One striking observation is that mutant KCNT1 causes abnormally large and spontaneous EJPs (sEJPs). Our data suggest that these sEJPs result from local depolarization of synaptic terminals due to a reduction in Shaker channel levels and more active Na+channels. Hence, we provide the firstin vivoevidence that both disinhibition of inhibitory neurons and compensatory plasticity in motoneurons can account for the paradoxical effects of gain-of-function mutant KCNT1 in epilepsy.
miR-128-induced LINE-1 restriction is dependent on down-regulation of hnRNPA1
Authors: Fung Lianna , Guzman Herlinda , Sevrioukov Evgueni , Idica Adam , Park Eddie , Bochnakien Aurore , Daugaard Iben , Jury Douglas , Mortazavi Ali , Zisoulis Dimitrios G , Pedersen Irene Munk
Published: October 2017

The majority of the human genome is made of transposable elements, giving rise to interspaced repeats, including Long Interspersed Element-1s (LINE-1s or L1s). L1s are active human DNA parasites involved in genomic diversity and evolution, but can also contribute to genomic instability and diseases. L1s require host factors to complete their life cycles, whereas the host has evolved numerous mechanisms to restrict L1-induced mutagenesis. Restriction mechanisms in somatic cells include methylation of the L1 promoter, anti-viral factors and RNA-mediated processes such as small RNAs. microRNAs (miRNAs or miRs) are small non-coding RNAs that post-transcriptionally repress multiple target genes often found in the same cellular pathways. We have recently established that the interferon-inducible miR-128 function as a novel restriction factor inhibiting L1 mobilization in somatic cells. We have further demonstrated that miR-128 function through a dual mechanism; by directly targeting L1 RNA for degradation and indirectly by inhibiting a cellular co-factor which L1 is dependent on to transpose to new genomic locations (TNPO1). Here we add another piece to the puzzle of the enigmatic L1 life cycle. We show that miR-128 also inhibits another key cellular factor, hnRNPA1, by significantly reducing mRNA and protein levels through direct interaction with the coding sequence (CDS) of hnRNPA1 mRNA. Furthermore, we demonstrate that repression of hnRNPA1 using shRNA significantly decreasesde novoL1 retrotransposition and that induced hnRNPA1 expression enhances L1 mobilization. Finally, we determine that hnRNPA1 is a functional target of miR-128 and that induced hnRNPA1 expression in miR-128-overexpressing cells can partly rescue the miR-128-induced repression of L1’s ability to transpose to different genomic locations. Thus, we have identified an additional mechanism by which miR-128 represses L1 retrotransposition and mediate genomic stability.
Atg8 is essential specifically for an autophagy-independent function in apicoplast biogenesis in blood-stage malaria parasites
Authors: Walczak Marta , Ganesan Suresh M. , Niles Jacquin C. , Yeh Ellen
Published: October 2017

Plasmodiumparasites and related pathogens contain an essential non-photosynthetic plastid organelle, the apicoplast, derived from secondary endosymbiosis. Intriguingly, a highly conserved eukaryotic protein, autophagy-related protein 8 (Atg8), has an autophagy-independent function in the apicoplast. Little is known about the novel apicoplast function of Atg8 and its importance in blood-stageP. falciparum. Using aP. falciparumstrain in which Atg8 expression was conditionally regulated, we showed thatPfAtg8 is essential for parasite replication. Significantly, growth inhibition caused by the loss ofPfAtg8 was reversed by addition of isopentenyl pyrophosphate (IPP), which was previously shown to rescue apicoplast defects inP. falciparum. Parasites deficient inPfAtg8, but growth rescued by IPP, had lost their apicoplast. We designed a suite of functional assays, including a new fluorescencein situhybridization (FISH) method for detection of the low-copy apicoplast genome, to interrogate specific steps in apicoplast biogenesis and detect apicoplast defects which preceded the block in parasite replication. Though protein import and membrane expansion of the apicoplast were unaffected, the apicoplast was not inherited by daughter parasites. Our findings demonstrate that, though multiple autophagy-dependent and independent functions have been proposed forPfAtg8, only its role in apicoplast biogenesis is essential. We propose thatPfAtg8 is required for fission or segregation of the apicoplast during parasite replication.
GeNets: A unified web platform for network-based analyses of genomic data
Authors: Li Taibo , Kim April , Rosenbluh Joseph , Horn Heiko , Greenfeld Liraz , An David , Zimmer Andrew , Liberzon Arthur , Bistline Jon , Natoli Ted , Li Yang , Tsherniak Aviad , Narayan Rajiv , Subramanian Aravind , Liefeld Ted , Wong Bang , Thompson Dawn , Calvo Sarah , Carr Steve , Boehm Jesse , Jaffe Jake , Mesirov Jill , Hacohen Nir , Regev Aviv , Lage Kasper
Published: October 2017

Functional genomics networks are widely used to identify unexpected pathway relationships in large genomic datasets. However, it is challenging to quantitatively compare the signal-to-noise ratio of different networks, the biology they describe, and to identify the optimal network to interpret a particular genetic dataset. Via GeNets users can train a machine-learning model (Quack) to make such comparisons; and they can execute, store, and share analyses of genetic and RNA sequencing datasets.
Offline Replay Supports Planning: fMRI Evidence from Reward Revaluation
Authors: Momennejad Ida , Ross Otto A. , Daw Nathaniel D. , Norman Kenneth A.
Published: October 2017

Making decisions in sequentially structured tasks requires integrating distally acquired information. The extensive computational cost of such integration challenges planning methods that integrate online, at decision time. Furthermore, it remains unclear whether “offline” integration during replay supports planning, and if so which memories should be replayed. Inspired by machine learning, we propose that (a) offline replay of trajectories facilitates integrating representations that guide decisions, and (b) unsigned prediction errors (uncertainty) trigger such integrative replay. We designed a 2-step revaluation task for fMRI, whereby participants needed to integrate changes in rewards with past knowledge to optimally replan decisions. As predicted, we found that (a) multi-voxel pattern evidence for off-task replay predicts subsequent replanning; (b) neural sensitivity to uncertainty predicts subsequent replay and replanning; (c) off-task hippocampus and anterior cingulate activity increase when revaluation is required. These findings elucidate how the brain leverages offline mechanisms in planning and goal-directed behavior under uncertainty.
Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs
Authors: Yoon Nara , Vander Velde Robert , Marusyk Andriy , Scott Jacob G.
Published: October 2017

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown.

To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups,ARandBR, each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics.

Specifically, based on a system of ordinary differential equations forARandBR, we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point,T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e.fΔt-long forDrugAand (1 –f) Δt-long forDrugBwith 0 ≤f≤ 1 and Δt≥ 0). We prove that the optimal duration of the initial stage, in which the first drug is administered,T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition.

We further analyzed the relationship between population makeup,, and the effect of each drug. We determine a critical ratio, which we term, at which the two drugs are equally effective. As the first stage of the optimal strategy is applied,changes monotonically toand then, during the second stage, remains atthereafter.

Beyond our analytic results, we explored an individual based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.
Competitive learning modulates memory consolidation during sleep
Authors: Antony James W. , Cheng Larry Y. , Pacheco Paula , Paller Ken A. , Norman Kenneth A.
Published: October 2017

Competition between memories can cause weakening of those memories. Here we investigated memory competition during sleep by presenting auditory cues that had been linked to two distinct picture-location pairs during wake. We manipulated competition during learning by requiring subjects to rehearse item pairs associated with the same sound either competitively (choosing to rehearse one over the other, leading to greater competition) or separately; we hypothesized that greater competition during learning would lead to greater competition when memories were cued during sleep. With separate-pair learning, we found that cueing benefited spatial retention. With competitive-pair learning, no benefit of cueing was observed on retention, but cueing impaired retention of well-learned pairs (where we expected strong competition). During sleep, post-cue beta power (16-30 Hz) indexed competition-based weakening and forgetting, whereas sigma power (11-16 Hz) indexed memory strengthening. These findings show that memory consolidation during sleep fundamentally engages competition and selective memory weakening.
Fast Virome Explorer: A Pipeline for Virus and Phage Identification and Abundance Profiling in Metagenomics Data
Authors: Tithi Saima Sultana , Jensen Roderick V. , Zhang Liqing
Published: October 2017

Identifying viruses and phages in a metagenomics sample has important implication in improving human health, preventing viral outbreaks, and developing personalized medicine. With the rapid increase in data files generated by next generation sequencing, existing tools for identifying and annotating viruses and phages in metagenomics samples suffer from expensive running time. In this paper, we developed a stand-alone pipeline, FastViromeExplorer, for rapid identification and abundance quantification of viruses and phages in big metagenomic data. Both real and simulated data validated FastViromeExplorer as a reliable tool to accurately identify viruses and their abundances in large data, as well as in a time efficient manner.
Hunters or gardeners? Linking community structure and function of trap-associated microbes to the nutrient acquisition strategy of a carnivorous plant
Authors: Sirová Dagmara , Bárta Jiří , Šimek Karel , Posch Thomas , Pech Jiří , Stone James , Borovec Jakub , Adamec Lubomír , Vrba Jaroslav
Published: October 2017

All higher eukaryotes live in a relationship with diverse microorganisms which colonize their bodily surfaces; plants are no exception. However, we still lack a satisfactory understanding of how these loosely associated microbiomes with immense diversity and functional potential interact with their hosts or how these interactions shape processes within populations and ecosystems. There is considerable similarity between microbial communities colonizing plant surfaces such as roots, and those of the animal gut. This often overlooked parallel allows us to look at microbial as well as host ecophysiology from a fresh perspective. The traps of carnivorous plants are sophisticated digestive organs and interface environments between the supply and the demand for nutrients. We selected the miniature ecosystem in the traps of aquatic carnivorousUtriculariaplants as our model system. By assessing the trap-associated microbial community structure, diversity, function, as well as the nutrient recycling potential of bacterivory, we gained insight into the nutrient acquisition strategies of theUtriculariahosts. We conclude that trap ecophysiological function is in many aspects highly analogous to that of the herbivore gut and centers around complex microbial consortia, which act synergistically to covert complex organic matter, often of algal origin, into a source of nutrients for the plants.
A radial pillar device (RAPID) for continuous and high-throughput separation of multi-sized particles
Authors: Mehendale Ninad , Sharma Oshin , D’Costa Claudy , Paul Debjani
Published: October 2017

Pillar-based microfluidic sorting devices are preferred for isolation of rare cells due to their simple designs and passive operation. Dead-end pillar filters can efficiently capture large rare cells, such as, circulating tumor cells (CTCs), nucleated red blood cells (NRBCs), etc., but they get clogged easily. Cross flow filters are preferred for smaller rare particles (e.g. separating bacteria from blood), but they need additional buffer inlets and a large device footprint for efficient operation. We have designed a new microparticle separation device i.e.RadialPillarDevice (RAPID) that combines the advantages of dead-end and cross flow filters. RAPID can simultaneously isolate both large and small rare particles from a mixed population, while functioning for several hours without clogging. We have achieved simultaneous separation of 10µm and 2µm polystyrene particles from a mixture of 2µm, 7µm and 10µm beads. RAPID achieved average separation purity and recovery in excess of ⟂ 90%. The throughput of our device (⟂ 3ml/min) is 10 and 100 times higher compared to cross flow and dead-end filters respectively, thereby justifying the name RAPID.
Assessing Selectivity in the Basal Ganglia: The “Gearbox” Hypothesis
Authors: Fountas Zafeirios , Shanahan Murray
Published: October 2017

Despite experimental evidence, the literature so far contains no systematic attempt to address the impact of cortical oscillations on the ability of the basal ganglia (BG) to select. In this study, we employed a state-of-the-art spiking neural model of the BG circuitry and investigated the effectiveness of this circuitry as an action selection device. We found that cortical frequency, phase, dopamine and the examined time scale, all have a very important impact on this process. Our simulations resulted in a canonical profile of selectivity, termed selectivity portraits, which suggests that the cortex is the structure that determines whether selection will be performed in the BG and what strategy will be utilized. Some frequency ranges promote the exploitation of highly salient actions, others promote the exploration of alternative options, while the remaining frequencies halt the selection process. Based on this behaviour, we propose that the BG circuitry can be viewed as the “gearbox” of action selection. Coalitions of rhythmic cortical areas are able to switch between a repertoire of available BG modes which, in turn, change the course of information flow within the cortico-BG-thalamo-cortical loop. Dopamine, akin to “control pedals”, either stops or initiates a decision, while cortical frequencies, as a “gear lever”, determine whether a decision can be triggered and what type of decision this will be. Finally, we identified a selection cycle with a period of around 200ms, which was used to assess the biological plausibility of the popular cognitive architectures.

Author summary

Our brains are continuously called to select the most appropriate action between alternative competing choices. A plethora of evidence and theoretical work indicates that a fundamental brain region called the basal ganglia might be the locus where this competition occurs. But how is the winning choice determined each time? Using a detailed computational model, based on neurophysiological properties of this region, we suggest that, whereas the basal ganglia might indeed contain the circuitry of action selection, the cerebral cortex is, in fact, the brain region that dictates this process. Similarly to a gearbox in a car, the basal ganglia provide modes for the exploitation of the safest option (forward gears), exploration of alternative options (reverse gear) and a neutral state, in case that the selection process needs to be halted. Our results further indicate that the instructions for mode-switching are relayed to the basal ganglia through specific low frequencies of oscillations within cortical areas. Finally, we provide estimations for the frequency ranges that can be used to activate each selectivity mode, as well as the duration of the selection process under various conditions.
Partial restoration of mutational robustness after addition of genetic polymorphism and in the presence of sexual selection
Authors: Nieberding Caroline M. , San Martin Gilles , Saenko Suzanne , Allen Cerisse E. , Brakefield Paul M. , Visser Bertanne
Published: October 2017

The interaction between mutational (i.e. genetic) robustness, cryptic genetic variation and epistasis is currently under much debate, as is the question whether mutational robustness evolved under direct selection or as a by-product of environmental robustness. Here we report that mutational robustness was restored in a mutant line of the butterflyBicyclus anynanaafter the spontaneous mutation,comet, appeared in a genetically polymorphic wild type population. Thecometmutation modified two phenotypic traits known to be under sexual selection in this butterfly: the dorsal forewing eyespot, which is normally round, but became ‘comet’-shaped, and the androconia, the structures producing the male sex pheromone, which were reduced in size. Thecometmutant line remained phenotypically stable for ∼7 seven years, but when outcrossed to the genetically polymorphic wild type population, the outcrossedcometline surprisingly recovered the wild type phenotype within 8 generations. This suggests that mutational robustness against thecometmutation was recovered in thecometoutcrossed line by epistatic interactions with the genetic polymorphism originating from wild types. The extent of wild type phenotype recovery in thecometoutcrossed line was trait- and developmental temperature-dependent, such that mutational robustness was partially recovered at high, but not at low developmental temperatures. We hypothesized that sexual selection through mate choice, which is sex-reversed between developmental temperatures in this butterfly, could produce mutational robustness at a high (but not at a low) temperature. Females are the choosy sex and exert stabilizing or directional selection on male secondary sexual wing traits but only at higher temperatures. Male mating success experiments under semi-natural conditions then revealed that males with the typicalcometmutant phenotype suffered from lower mating success compared to wild type males, while mating success ofcometmales resembling wild types was partially restored. Altogether, we document the roles of cryptic genetic variation and epistasis in restoration of mutational robustness against a spontaneous mutation with known fitness effects, and we provide experimental evidence, for the first time to our knowledge, that sexual selection can produce mutational robustness.
The plastid-nucleus located DNA/RNA binding protein WHIRLY1 regulates microRNA-levels during stress
Authors: Swida-Barteczka Aleksandra , Krieger-Liszkay Anja , Bilger Wolfgang , Voigt Ulrike , Hensel Götz , Szweykowska-Kulinska Zofia , Krupinska Karin
Published: October 2017

In this article a novel mechanism of retrograde signaling by chloroplasts during stress is described. This mechanism involves the DNA/RNA binding protein WHIRLY1 as a regulator of microRNA levels. By virtue of its dual localization in chloroplasts and the nucleus of the same cell, WHIRLY1 was proposed as an excellent candidate coordinator of chloroplast function and nuclear gene expression (Grabowski et al., 2008; Foyer et al., 2014). In this study the putative involvement of WHIRLY1 in stress dependent retrograde signaling was investigated by comparison of barley (Hordeum vulgareL., cv. Golden Promise) wild-type and transgenic plants with an RNAi-mediated knockdown ofWHIRLY1. In contrast to the wild type, the transgenic plants were unable to cope with continuous high light conditions. They were impaired in production of several microRNAs mediating post-transcriptional responses during stress (Kruszka et al., 2012, Sunkar et al., 2012). The results support a central role of WHIRLY1 in retrograde signaling and underpin a so far underestimated role of microRNAs in this process.
DNA-Demethylating Agents enhance cytolytic activity of CD8+ T Cells and anti-tumor immunity
Authors: Yau Helen Loo , Chakravarthy Ankur , Almeida Felipe Campos de , Allard David , Singhania Rajat , Ettayebi Ilias , Shen Shu Yi , Medina Tiago , Mehdipour Parinaz , Morancho Beatriz , Pommey Sandra , Klein Christian , Amarante-Mendes Gustavo , Roulois David , Butler Marcus , Arribas Joaquín , Stagg John , De Carvalho Daniel D.
Published: October 2017

Recent studies have shown that DNA methyltransferase inhibitors (DNMTi) can induce IRF7 activation and Type I/III interferon signaling through dsRNA-mediated viral mimicry in cancer cells. By performing a large pan-cancer analysis using TCGA data, we determined that IRF7 activation is associated with higher CD8+ T cell tumor infiltration and higher cytolytic activity across multiple cancer types. Accordingly, we demonstrate that DNMTi treatment results in increased CD8+ T cell tumor infiltration, enhanced cytolytic activity and CD8+ T cell dependent tumor growth inhibition. Finally, we show that DNMTi triggers a process marked by the induction of viral mimicry directly on CD8+ T cells, leading to activation of dsRNA sensing pathway, and up-regulation of T cell activation markers, effector cytokines, and Granzyme B. Taken together, our findings suggest that dsRNA sensing pathway activation in the immune compartment, through pharmacological DNA demethylation, is a viable strategy for boosting anti-tumor immune response.
Probing transcription factor combinatorics in different promoter classes and in enhancers
Authors: Vandel Jimmy , Cassan Océane , Lèbre Sophie , Lecellier Charles-Henri , Bréhélin Laurent
Published: October 2017

In eukaryotic cells, transcription factors (TFs) are thought to act in a combinatorial way, by competing and collaborating to regulate common target genes. However, several questions remain regarding the conservation of these combina-tions among different gene classes, regulatory regions and cell types. We propose a new approach named TFcoop to infer the TF combinations involved in the binding of a tar-get TF in a particular cell type. TFcoop aims to predict the binding sites of the target TF upon the binding affinity of all identified cooperating TFs. The set of cooperating TFs and model parameters are learned from ChIP-seq data of the target TF. We used TFcoop to investigate the TF combina-tions involved in the binding of 106 TFs on 41 cell types and in four regulatory regions: promoters of mRNAs, lncRNAs and pri-miRNAs, and enhancers. We first assess that TFcoop is accurate and outperforms simple PWM methods for pre-dicting TF binding sites. Next, analysis of the learned models sheds light on important properties of TF combinations in different promoter classes and in enhancers. First, we show that combinations governing TF binding on enhancers are more cell-type specific than that governing binding in pro-moters. Second, for a given TF and cell type, we observe that TF combinations are different between promoters and en-hancers, but similar for promoters of mRNAs, lncRNAs and pri-miRNAs. Analysis of the TFs cooperating with the dif-ferent targets show over-representation of pioneer TFs and a clear preference for TFs with binding motif composition similar to that of the target. Lastly, our models accurately dis-tinguish promoters associated with specific biological processes.
Deep Convolutional Neural Networks Enable Discrimination of Heterogeneous Digital Pathology Images
Authors: Khosravi Pegah , Kazemi Ehsan , Imielinski Marcin , Elemento Olivier , Hajirasouliha Iman
Published: October 2017

Pathological evaluation of tumor tissue is pivotal for diagnosis in cancer patients and automated image analysis approaches have great potential to increase precision of diagnosis and help reduce human error. In this study, we utilize various computational methods based on convolutional neural networks (CNN) and build a stand-alone pipeline to effectively classify different histopathology images across different types of cancer. In particular, we demonstrate the utility of our pipeline to discriminate between two subtypes of lung cancer, four biomarkers of bladder cancer, and five biomarkers of breast cancer. In addition, we apply our pipeline to discriminate among four immunohistochemistry (IHC) staining scores of bladder and breast cancers.
Our classification pipeline utilizes a basic architecture of CNN, Google's Inceptions within three training strategies, and an ensemble of two state-of-the-art algorithms, Inception and ResNet. These strategies include training the last layer of Google's Inceptions, training the network from scratch, and fine-tunning the parameters for our data using two pre-trained version of Google's Inception architectures, Inception-V1 and Inception-V3.
We demonstrate the power of deep learning approaches for identifying cancer subtypes, and the robustness of Google's Inceptions even in presence of extensive tumor heterogeneity. Our pipeline on average achieved accuracies of 100% , 92%, 95%, and 69% for discrimination of various cancer types, subtypes, biomarkers, and scores, respectively. Our pipeline and related documentation is freely available at https://github.com/ih-lab/CNN_Smoothie
TAp73 is a marker of glutamine addiction in medulloblastoma
Authors: Niklison-Chirou Maria Victoria , Erngren Ida , Engskog Mikael , Haglöf Jakob , Picard Daniel , Remke Marc , McPolin Phelim Hugh Redmond , Selby Matthew , Williamson Daniel , Clifford Steven C. , Michod David , Hadjiandreou Michalis , Arvidsson Torbjörn , Pettersson Curt , Melino Gerry , Marino Silvia
Published: October 2017

Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma.