bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping queer ‘celebratory moment’ in India: necropolitics or substantive democracy?
Authors: Kumar Pushpesh
Published: December 2019

Using the theoretical framework of queer necropolitics indicating the negation of subjecthood to trans-queer of colour while assimilating white privileged gays through homonormative gestures like marriage and domesticity in the USA, the paper compares the diverse reactions of the Indian ‘urban corporate gay’ constituency and the marginalized transgender communities following the legalization of ‘homosexuality’ in India recently. Through an analysis of social media texts from the former and reflections of the latter, I propose a ‘critical intersectionality’ to politicize the idea of queer community mobilizations in India. While critically reflecting on the limits of ‘consumer citizenship’ of the privileged gay, the paper attempts to foreground the voices of transgender ‘counterpublics’ to draw attention to and problematize the idea of ‘community’ (re)iterated through popular and legal discourses.
Radial Glial Cell-Derived VCAM1 Regulates Cortical Angiogenesis Through Distinct Enrichments in the Proximal and Distal Radial Processes
Authors: Zhang Sanguo , Wang Huanhuan Joyce , Li Jia , Hu Xiao-Ling , Shen Qin
Published: December 2019

Angiogenesis in the developing cerebral cortex accompanies cortical neurogenesis. However, the precise mechanisms underlying cortical angiogenesis at the embryonic stage remain largely unknown. Here, we show that radial glia-derived vascular cell adhesion molecule 1 (VCAM1) coordinates cortical vascularization through different enrichments in the proximal and distal radial glial processes. We found that VCAM1 was highly enriched around the blood vessels in the inner ventricular zone (VZ), preventing the ingrowth of blood vessels into the mitotic cell layer along the ventricular surface. Disrupting the enrichment of VCAM1 surrounding the blood vessels by a tetraspanin-blocking peptide or conditional deletion of Vcam1 gene in neural progenitor cells increased angiogenesis in the inner VZ. Conversely, VCAM1 expressed in the basal endfeet of radial glial processes promoted angiogenic sprouting from the perineural vascular plexus (PNVP). In utero, overexpression of VCAM1 increased the vessel density in the cortical plate, while knockdown of Vcam1 accomplished the opposite. In vitro, we observed that VCAM1 bidirectionally affected endothelial cell proliferation in a concentration-dependent manner. Taken together, our findings identify that distinct concentrations of VCAM1 around VZ blood vessels and the PNVP differently organize cortical angiogenesis during late embryogenesis.
The Mystery of “Metal Mouth” in Chemotherapy
Authors: Reith Alastair J M , Spence Charles
Published: December 2019

Of all the oral sensations that are experienced, “metallic” is one that is rarely reported in healthy participants. So why, then, do chemotherapy patients so frequently report that “metallic” sensations overpower and interfere with their enjoyment of food and drink? This side-effect of chemotherapy—often referred to (e.g., by patients) as “metal mouth”—can adversely affect their appetite, resulting in weight loss, which potentially endangers (or at the very least slows) their recovery. The etiology of “metal mouth” is poorly understood, and current management strategies are largely unevidenced. As a result, patients continue to suffer as a result of this poorly understood phenomenon. Here, we provide our perspective on the issue, outlining the evidence for a range of possible etiologies, and highlighting key research questions. We explore the evidence for “metallic” as a putative taste, and whether “metal mouth” might therefore be a form of phantageusia, perhaps similar to already-described “release-of-inhibition” phenomena. We comment on the possibility that “metal mouth” may simply be a direct effect of chemotherapy drugs. We present the novel theory that “metal mouth” may be linked to chemotherapy-induced sensitization of TRPV1. Finally, we discuss the evidence for retronasal olfaction of lipid oxidation products in the etiology of “metal mouth.” This article seeks principally to guide much-needed future research which will hopefully one day provide a basis for the development of novel supportive therapies for future generations of patients undergoing chemotherapy.
Musculoskeletal pain reported by mobile patients with chronic kidney disease
Authors: Molsted Stig , Eidemak Inge
Published: December 2019

Background

Musculoskeletal pain has been reported as a clinical problem in patients with chronic kidney disease (CKD). The purpose of this study was to compare the frequency of musculoskeletal pain in patients with CKD and no mobility problems with a general population and to investigate the impact of pain on quality of life (QOL), physical activity and physical function.

Methods

Patients with CKD Stages 4 and 5 with or without a dialysis treatment and no mobility problems were included. Musculoskeletal pain in the shoulder/neck, back/low back and limbs and level of physical activity were measured using the Danish Health and Morbidity Survey and coded into dichotomous answers. QOL and physical function were measured using the kidney disease QOL questionnaire and the 30-s chair stand test, respectively. Data for the general population were collected in national registers and adjusted for age, gender and region.

Results

The patients (n = 539) had a mean age of 66 [95% confidence interval (CI) 65–67] years, 62% were men and they were treated with haemodialysis (HD) (n = 281), peritoneal dialysis (n = 62) or without dialysis (n = 196). The frequency of reported musculoskeletal pain in the patients did not exceed pain reported by the general population [e.g. pain in the limbs in patients undergoing HD versus a matched general population, 61% versus 63% (P = 0.533), respectively]. Pain in all measured body sites was associated with reduced QOL [e.g. pain in the limbs associated with a physical component scale β of −8.2 (95% CI −10.3 to −6.0), P < 0.001]. Pain in the limbs was associated with a reduced number of repetitions in the 30-s chair stand test [mean −1.7 (95% CI −3.0 to −0.4), P = 0.009]. Pain in the shoulder/neck was associated with reduced odds of being physically active [odds ratio 0.6 (95% CI 0.4 to 0.9); P = 0.022].

Conclusions

Musculoskeletal pain was not more frequently reported by patients with CKD and no mobility problems compared with the general population. However, as musculoskeletal pain was reported by up to two-thirds of the patient sample, healthcare professionals should remember to focus on this issue. The patients’ pain was associated with negative impacts on QOL, level of physical activity and physical function.
Secure Outsourcing Algorithms for Composite Modular Exponentiation Based on Single Untrusted Cloud
Authors: Su Qianqian , Zhang Rui , Xue Rui
Published: December 2019

Modular exponentiation, as a fundamental operation used in many public-key cryptosystems, has always be considered to be very time-consuming. It is difficult for some devices with limited computation capability, such as mobile devices and low-cost radio frequency identification (RFID) tags, to perform large-scale modular exponentiations. In cryptosystems, one typical case of modular exponentiation is that the modulus is a composite number. For instance, in RSA algorithm, the modulus is the product of two distinct prime numbers. In this paper, we investigate how to securely and efficiently outsource composite modular exponentiations and put forward two secure outsourcing algorithms for composite modular exponentiations based on single untrusted cloud. The first algorithm, named MCExp, is designed for outsourcing single composite modular exponentiation, i.e. $u^a$ mod $N$. The second algorithm, named SMCExp, is designed for outsourcing simultaneous composite modular exponentiation, i.e. $\prod ^{n}_{i=1}u^{a_i}_{i}$ mod $N$. Different from algorithms based on two untrusted servers, the proposed algorithms are very practical because they avoid the strong assumption that there must exist two servers without collusion. The proposed algorithms not only protect the privacy of the exponent and the base simultaneously, but also enable users to verify the correctness of the result returned by the cloud with high probability. Compared with using the square-and-multiply algorithm, the user can achieve higher efficiency by using the proposed algorithms. Besides, we prove the security of our algorithms and conduct several experiments to demonstrate the efficiency of the proposed algorithms. Finally, we show that the proposed algorithms can be used to construct the secure outsourcing algorithms for Shamir’s identity-based signature and identity-based multi-signature.
Pinniped predation of birds: A cause for conservation concern?
Authors: Swan George J F , Silva-Rodríguez Eduardo A , Osman Layla P , Jaramillo Eduardo
Published: December 2019

Recovering predators can create challenges for conservation objectives when they prey on vulnerable species. Although largely uncommon, pinniped predation of birds presents one such challenge. Here, we describe the novel characteristics of this predator–prey interaction, its impact on bird populations, and possible mitigation responses. We do so both broadly, synthesizing the wider literature, and specifically, in reference to ongoing South American sea lion (Otaria flavescens) predation of Black-necked Swans (Cygnus melancoryphus) we are currently observing in southern Chile. Our review of the literature suggests that in most cases bird predation by pinnipeds is only exhibited by a small proportion of the population, spreads socially between individuals, can be temporally severe, and may rapidly threaten the viability of bird populations. We discuss feasibility and efficacy of potential mitigation measures highlighting that, as foraging specializations can be socially transmitted, any such actions need to be time conscious as bird-killing behaviors may be increasingly difficult to remove. The contrasting population trends of pinnipeds and seabirds suggests that pinniped predation of vulnerable waterbirds is going to be an increasingly common conservation challenge in the future.
Fish consumption is associated with school performance in children in a non-linear way
Authors: Lehner A , Staub K , Aldakak L , Eppenberger P , Rühli F , Martin R D , Bender N
Published: December 2019

Introduction

How the long-chain fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in the diet permitted human brain evolution, and how much our brains need today to function optimally are still hot topics for debate. DHA and EPA are considered as semi-essential because only insufficient amounts can be produced from other nutrients, such that they must be ingested with the diet. However, the Dietary Reference Intake of DHA and EPA, or of fish containing these fatty acids, has not yet been established. Eating fish is often recommended and generally considered beneficial for health and cognitive development in children and adolescents. For this study, data from a large cohort study were analysed to assess the association between fish consumption and cognitive school performance in children and adolescents.

Methods

Data from the German cohort of children and adolescent health KiGGS, which was conducted 2003–06 and included more than 17 000 children, were analysed. Ordered logistic regressions were performed to test for associations between fish intake and school performance. Potential confounders were included in the models.

Results

A statistically significant association was found between an intake of 8 g of fish per day and the probability of increasing the final grade in German [odds ratio (OR) 1.193, 95% confidence interval (CI) 1.049–1.358] and mathematics (OR 1.16, 95% CI 1.022–1.317) by one point, compared to no or very limited fish consumption. For the outcome German, higher levels of fish intake also showed a positive effect. These relationships were not linear but tended to decrease again at higher doses of fish.

Discussion

Our result confirms previous reports of a positive association between fish intake and school performance. Interestingly, this relationship was not linear but tended to decrease again in the highest categories of fish intake. We hypothesize that mercury or other pollutants in the fish could be detrimental at high levels. As only half of all children met the minimal fish intake recommendations, fish consumption should be promoted more strongly in children to meet the minimal requirements of long-chain polyunsaturated fatty acids.

Lay Summary

Polyunsaturated fatty acids like DHA and EPA that are present in fish are essential for a healthy human brain development. We found a U-shaped association between fish intake and school performance in children. We hypothesize that mercury or other pollutants in the fish could be detrimental at high intake levels.
A novel multielectrode catheter for high-density ventricular mapping: electrogram characterization and utility for scar mapping
Authors: Barkagan Michael , Sroubek Jakub , Shapira-Daniels Ayelet , Yavin Hagai , Jang Jihye , Nezafat Reza , Anter Elad
Published: December 2019

Aims

Multielectrode mapping catheters can be advantageous for identifying surviving myocardial bundles in scar. This study aimed to evaluate the utility of a new multielectrode catheter with increased number of small and closely spaced electrodes for mapping ventricles with healed infarction.

Methods and results

In 12 swine (four healthy and eight with infarction), the left ventricle was mapped with investigational (OctarayTM) and standard (PentarayTM) multielectrode mapping catheters. The investigational catheter has more electrodes (48 vs. 20), each with a smaller surface area (0.9 vs. 2.0 mm2) and spacing is fixed at 2 mm (vs. 2–6–2 mm). Electrogram (EGM) characteristics, mapping efficiency and scar description were compared between the catheters and late gadolinium enhancement (LGE). Electrogram acquisition rate was faster with the investigational catheter (814 ± 126 vs. 148 ± 58 EGM/min, P = 0.02) resulting in higher density maps (38 ± 10.3 vs. 10.1 ± 10.4 EGM/cm2, P = 0.02). Bipolar voltage amplitude was similar between the catheters in normal and infarcted myocardium (P = 0.265 and P = 0.44) and the infarct surface area was similar between the catheters (P = 0.12) and corresponded to subendocardial LGE. The investigational catheter identified a higher proportion of near-field local abnormal ventricular activities within the low-voltage area (53 ± 16% vs. 34 ± 16%, P = 0.03) that were considered far-field EGMs by the standard catheter. The investigational catheter was also advantageous for mapping haemodymically non-tolerated ventricular tachycardias due to its higher acquisition rate (P < 0.001).

Conclusion

A novel multielectrode mapping catheter with higher number of small, and closely spaced electrodes increases the mapping speed, EGM density and the ability to recognize low amplitude near-field EGMs in ventricles with healed infarction.
Thermal softening induced subduction initiation at a passive margin
Authors: Kiss Dániel , Candioti Lorenzo G , Duretz Thibault , Schmalholz Stefan M
Published: December 2019

We present 2-D numerical simulations of convergence at a hyperextended passive margin with exhumed subcontinental mantle. We consider viscoelasto-plastic deformation, heat transfer and thermomechanical coupling by shear heating and associated thermal softening due to temperature dependent viscosity. The simulations show subduction initiation for convergence velocities of 2 cm yr−1, initial Moho temperatures of 525 °C and maximal deviatoric stresses of ca. 800 MPa, around the Moho, prior to localization. Subduction initiates in the region with thinned continental crust and is controlled by a thermally activated ductile shear zone in the mantle lithosphere. The shear zone temperature can be predicted with a recently published analytical expression. The criterion for subduction initiation is a temperature difference of at least 225 °C between predicted temperature and initial Moho temperature. The modelled forced subduction broadly agrees with geological data and reconstructions of subduction during closure of the Piemont-Liguria basin, caused by convergence of the European and Adriatic plates during the Alpine orogeny.
Using statutory health insurance data to evaluate non-response in a cross-sectional study on depression among patients with diabetes in Germany
Authors: Linnenkamp Ute , Gontscharuk Veronika , Brüne Manuela , Chernyak Nadezda , Kvitkina Tatjana , Arend Werner , Fiege Annett , Schmitz-Losem Imke , Kruse Johannes , Evers Silvia M A A , Hiligsmann Mickaël , Hoffmann Barbara , Andrich Silke , Icks Andrea
Published: December 2019

Background

Low response rates do not indicate poor representativeness of study populations if non-response occurs completely at random. A non-response analysis can help to investigate whether non-response is a potential source for bias within a study.

Methods

A cross-sectional survey among a random sample of a health insurance population with diabetes (n = 3642, 58.9% male, mean age 65.7 years), assessing depression in diabetes, was conducted in 2013 in Germany. Health insurance data were available for responders and non-responders to assess non-response bias. The response rate was 51.1%. Odds ratios (ORs) for responses to the survey were calculated using logistic regression taking into consideration the depression diagnosis as well as age, sex, antihyperglycaemic medication, medication utilization, hospital admission and other comorbidities (from health insurance data).

Results

Responders and non-responders did not differ in the depression diagnosis [OR 0.99, confidence interval (CI) 0.82–1.2]. Regardless of age and sex, treatment with insulin only (OR 1.73, CI 1.36–2.21), treatment with oral antihyperglycaemic drugs (OAD) only (OR 1.77, CI 1.49–2.09), treatment with both insulin and OAD (OR 1.91, CI 1.51–2.43) and higher general medication utilization (1.29, 1.10–1.51) were associated with responding to the survey.

Conclusion

We found differences in age, sex, diabetes treatment and medication utilization between responders and non-responders, which might bias the results. However, responders and non-responders did not differ in their depression status, which is the focus of the DiaDec study. Our analysis may serve as an example for conducting non-response analyses using health insurance data.
Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus–Infected Women Despite Immune Reconstitution With Antiretroviral Therapy
Authors: Thomas Archana , Hammarlund Erika , Gao Lina , Holman Susan , Michel Katherine G , Glesby Marshall , Villacres Maria C , Golub Elizabeth T , Roan Nadia R , French Audrey L , Augenbraun Michael H , Slifka Mark K
Published: December 2019

Background

It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections.

Methods

We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA).

Results

There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24–108 years; P = .001).

Conclusions

Despite antiretroviral therapy–associated improvement in CD4+ T-cell counts (nadir, <200/μL; >350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.
Biallelic variants/mutations ofIL1RAPin patients with steroid-sensitive nephrotic syndrome
Authors: Niitsuma Sou , Kudo Hiroki , Kikuchi Atsuo , Hayashi Takaya , Kumakura Satoshi , Kobayashi Shuhei , Okuyama Yuko , Kumagai Naonori , Niihori Tetsuya , Aoki Yoko , So Takanori , Funayama Ryo , Nakayama Keiko , Shirota Matsuyuki , Kondo Shuji , Kagami Shoji , Tsukaguchi Hiroyasu , Iijima Kazumoto , Kure Shigeo , Ishii Naoto
Published: December 2019

Nephrotic syndrome (NS) is a renal disease characterized by severe proteinuria and hypoproteinemia. Although several single-gene mutations have been associated with steroid-resistant NS, causative genes for steroid-sensitive NS (SSNS) have not been clarified. While seeking to identify causative genes associated with SSNS by whole-exome sequencing, we found compound heterozygous variants/mutations (c.524T>C; p.I175T and c.662G>A; p.R221H) of the interleukin-1 receptor accessory protein (IL1RAP) gene in two siblings with SSNS. The siblings’ parents are healthy, and each parent carries a different heterozygous IL1RAP variant/mutation. Since IL1RAP is a critical subunit of the functional interleukin-1 receptor (IL-1R), we investigated the effect of these variants on IL-1R subunit function. When stimulated with IL-1β, peripheral blood mononuclear cells from the siblings with SSNS produced markedly lower levels of cytokines compared with cells from healthy family members. Moreover, IL-1R with a variant IL1RAP subunit, reconstituted on a hematopoietic cell line, had impaired binding ability and low reactivity to IL-1β. Thus, the amino acid substitutions in IL1RAP found in these NS patients are dysfunctional variants/mutations. Furthermore, in the kidney of Il1rap−/− mice, the number of myeloid-derived suppressor cells, which require IL-1β for their differentiation, was markedly reduced although these mice did not show significantly increased proteinuria in acute nephrotic injury with lipopolysaccharide treatment. Together, these results identify two IL1RAP variants/mutations in humans for the first time and suggest that IL1RAP might be a causative gene for familial NS.
The EUCAST rapid disc diffusion method for antimicrobial susceptibility testing directly from positive blood culture bottles
Authors: Jonasson Emma , Matuschek Erika , Kahlmeter Gunnar
Published: December 2019

Objectives

With increasing antimicrobial resistance, rapid antimicrobial susceptibility testing (RAST) becomes important, especially in patients with bloodstream infections. EUCAST decided to develop a standardized rapid method, based on EUCAST disc diffusion, to offer susceptibility reports within 4–8 h of a positive blood culture (BC).

Methods

BC bottles were spiked with clinical isolates (n = 332) of the seven most relevant sepsis pathogens with a variety of resistance mechanisms. RAST was performed directly from the bottle and zones read after 4, 6 and 8 h. Several variables were investigated, including the effect of using different BC bottles and of a 0–18 h delay between a positive signal and the performance of RAST.

Results

For five species, most inhibition zones could be read after 4 h. The proportion of results that could be interpreted increased from 75% at 4 h to 84% after 8 h. Categorical agreement against the reference method was good, with error rates of false susceptibility of 0.2%, 0.2% and 0.2% at 4, 6 and 8 h and false resistance of 1.2%, 0.2% and 0.1% at 4, 6 and 8 h, respectively.

Conclusions

With the EUCAST RAST method, reliable AST results can be delivered within 4–8 h of positivity of BC bottles for seven important bloodstream infection pathogens. To reduce the occurrence of errors and to absorb the variability caused by using a non-standardized inoculum, material from different manufacturers and workflow-related delays, we have introduced an area in which interpretation is not permitted, the Area of Technical Uncertainty.
Magnetic activity and evolution of the four Hyades K giants
Authors: Schröder K-P , Mittag M , Jack D , Rodríguez Jiménez A , Schmitt J H M M
Published: December 2019

We determine the exact physical parameters of the four Hyades cluster K giants, using their parallaxes and atmospheric modelling of our red-channel TIGRE high-resolution spectra. Performing a comparison with well-tested evolutionary tracks, we derive exact masses and evolutionary stages. At an age of 588 (±60) Myr and with a metallicity of Z = 0.03 (consistent with the spectroscopic abundances), we find HD 27371 and HD 28307, the two less bright K giants, at the onset of central helium burning, entering their blue loops with a mass of 2.62 M⊙, while the slightly brighter stars HD 28305 and HD 27697 are already exiting their blue loop. Their more advanced evolution suggests a higher mass of 2.75 M⊙. Notably, this pairing coincides with the different activity levels, which we find for these four stars from chromospheric activity monitoring with TIGRE and archival Mount Wilson data as well as from ROSAT coronal detections. The two less evolved K giants are the far more active pair, and we confidently confirm their rotation with periods of about 142 d. This work therefore provides some first, direct evidence of magnetic braking during the 130 Myr lasting phase of central helium-burning, similar to what has long been known to occur to cool main-sequence stars.
Resolved Lyman-α properties of a luminous Lyman-break galaxy in a large ionized bubble at z = 6.53
Authors: Matthee Jorryt , Sobral David , Gronke Max , Pezzulli Gabriele , Cantalupo Sebastiano , Röttgering Huub , Darvish Behnam , Santos Sérgio
Published: December 2019

The observed properties of the Lyman-α (Ly α) emission line are a powerful probe of neutral gas in and around galaxies. We present spatially resolved Ly α spectroscopy with VLT/MUSE targeting VR7, a UV-luminous galaxy at z = 6.532 with moderate Ly α equivalent width (EW0 ≈ 38 Å). These data are combined with deep resolved [CII]158μm spectroscopy obtained with ALMA and UV imaging from HST and we also detect UV continuum with MUSE. Ly α emission is clearly detected with S/N ≈ 40 and FWHM of 374 km s−1. Ly α and [C ii] are similarly extended beyond the UV, with effective radius reff = 2.1 ± 0.2 kpc for a single exponential model or r$_{\rm eff, Ly\alpha , halo} = 3.45^{+1.08}_{-0.87}$ kpc when measured jointly with the UV continuum. The Ly α profile is broader and redshifted with respect to the [C ii] line (by 213 km s−1), but there are spatial variations that are qualitatively similar in both lines and coincide with resolved UV components. This suggests that the emission originates from two components with plausibly different H i column densities. We place VR7 in the context of other galaxies at similar and lower redshift. The Ly α halo scale length is similar at different redshifts and velocity shifts with respect to the systemic are typically smaller. Overall, we find little indications of a more neutral vicinity at higher redshift. This means that the local (∼10 kpc) neutral gas conditions that determine the observed Ly α properties in VR7 resemble the conditions in post-reionization galaxies.
Sensitivity analysis of a galaxy formation model
Authors: Oleśkiewicz Piotr , Baugh Carlton M
Published: December 2019

We present the first application of a variance-based sensitivity analysis (SA) to a model that aims to predict the evolution and properties of the whole galaxy population. SA is a well-established technique in other quantitative sciences, but is a relatively novel tool for the evaluation of astrophysical models. We perform a multiparameter exploration of the GALFORM semi-analytic galaxy formation model, to compute how sensitive the present-day K-band luminosity function is to varying different model parameters. The parameter space is scanned using a low-discrepancy sampling technique proposed by Saltelli. We first demonstrate the usefulness of the SA approach by varying just two model parameters, one that controls supernova feedback and the other the heating of gas by active galactic nucleus. The SA analysis matches our physical intuition regarding how these parameters affect the predictions for different parts of the galaxy luminosity function. We then use SA to compute Sobol’ sensitivity indices varying seven model parameters, connecting the variance in the model output to the variance in the input parameters. The sensitivity is computed in luminosity bins, allowing us to probe the origin of the model predictions in detail. We discover that the SA correctly identifies the least important and most important parameters. Moreover, the SA also captures the combined responses of varying multiple parameters at the same time. Our study marks a much needed step away from the traditional 'one-at-a-time' parameter variation often used in this area and improves the transparency of multiparameter models of galaxy formation.
Post-main-sequence debris from rotation-induced YORP break-up of small bodies – II. Multiple fissions, internal strengths, and binary production
Authors: Veras Dimitri , Scheeres Daniel J
Published: December 2019

Over one-quarter of white dwarfs contain observable metallic debris from the break-up of exo-asteroids. Understanding the physical and orbital history of this debris would enable us to self-consistently link planetary system formation and fate. One major debris reservoir is generated by YORP-induced rotational fission during the giant branch phases of stellar evolution, where the stellar luminosity can exceed the Sun’s by four orders of magnitude. Here, we determine the efficacy of the giant branch YORP effect for asteroids with non-zero internal strength, and model post-fission evolution by imposing simple analytic fragmentation prescriptions. We find that even the highest realistic internal strengths cannot prevent the widespread fragmentation of asteroids and the production of a debris field over 100 au in size. We compute the number of successive fission events as they occur in progressively smaller time intervals as the star ascends the giant branches, providing a way to generate size distributions of asteroid fragments. The results are highly insensitive to progenitor stellar mass. We also conclude that the ease with which giant branch YORP break-up can generate binary asteroid subsystems is strongly dependent on internal strength. Formed binary subsystems in turn could be short-lived due to the resulting luminosity-enhanced binary YORP (BYORP) effect.
The performance of photometric reverberation mapping at high redshift and the reliability of damped random walk models
Authors: Read S C , Smith D J B , Jarvis M J , Gürkan G
Published: December 2019

Accurate methods for reverberation mapping using photometry are highly sought after since they are inherently less resource intensive than spectroscopic techniques. However, the effectiveness of photometric reverberation mapping for estimating black hole masses is sparsely investigated at redshifts higher than z ≈ 0.04. Furthermore, photometric methods frequently assume a damped random walk (DRW) model, which may not be universally applicable. We perform photometric reverberation mapping using the javelin photometric DRW model for the QSO SDSS-J144645.44+625304.0 at z = 0.351 and estimate the Hβ lag of $65^{+6}_{-1}$ d and black hole mass of $10^{8.22^{+0.13}_{-0.15}}\, \mathrm{M_{\odot }}$. An analysis of the reliability of photometric reverberation mapping, conducted using many thousands of simulated CARMA process light curves, shows that we can recover the input lag to within 6 per cent on average given our target’s observed signal-to-noise of >20 and average cadence of 14 d (even when DRW is not applicable). Furthermore, we use our suite of simulated light curves to deconvolve aliases and artefacts from our QSO’s posterior probability distribution, increasing the signal-to-noise on the lag by a factor of ∼2.2. We exceed the signal-to-noise of the Sloan Digital Sky Survey Reverberation Mapping Project (SDSS-RM) campaign with a quarter of the observing time per object, resulting in a ∼200 per cent increase in signal-to-noise efficiency over SDSS-RM.
Deep Residual Neural Networks Resolve Quartet Molecular Phylogenies
Authors: Zou Zhengting , Zhang Hongjiu , Guan Yuanfang , Zhang Jianzhi
Published: December 2019

Phylogenetic inference is of fundamental importance to evolutionary as well as other fields of biology, and molecular sequences have emerged as the primary data for this task. Although many phylogenetic methods have been developed to explicitly take into account substitution models of sequence evolution, such methods could fail due to model misspecification or insufficiency, especially in the face of heterogeneities in substitution processes across sites and among lineages. In this study, we propose to infer topologies of four-taxon trees using deep residual neural networks, a machine learning approach needing no explicit modeling of the subject system and having a record of success in solving complex nonlinear inference problems. We train residual networks on simulated protein sequence data with extensive amino acid substitution heterogeneities. We show that the well-trained residual network predictors can outperform existing state-of-the-art inference methods such as the maximum likelihood method on diverse simulated test data, especially under extensive substitution heterogeneities. Reassuringly, residual network predictors generally agree with existing methods in the trees inferred from real phylogenetic data with known or widely believed topologies. Furthermore, when combined with the quartet puzzling algorithm, residual network predictors can be used to reconstruct trees with more than four taxa. We conclude that deep learning represents a powerful new approach to phylogenetic reconstruction, especially when sequences evolve via heterogeneous substitution processes. We present our best trained predictor in a freely available program named Phylogenetics by Deep Learning (PhyDL, https://gitlab.com/ztzou/phydl; last accessed January 3, 2020).
Tat IRES modulator of tat mRNA (TIM-TAM): a conserved RNA structure that controls Tat expression and acts as a switch for HIV productive and latent infection
Authors: Khoury Georges , Mackenzie Charlene , Ayadi Lilia , Lewin Sharon R , Branlant Christiane , Purcell Damian F J
Published: December 2019

Tat protein is essential to fully activate HIV transcription and processing of viral mRNA, and therefore determines virus expression in productive replication and the establishment and maintenance of latent infection. Here, we used thermodynamic and structure analyses to define a highly conserved sequence-structure in tat mRNA that functions as Tat IRES modulator of tat mRNA (TIM-TAM). By impeding cap-dependent ribosome progression during authentic spliced tat mRNA translation, TIM-TAM stable structure impacts on timing and level of Tat protein hence controlling HIV production and infectivity along with promoting latency. TIM-TAM also adopts a conformation that mediates Tat internal ribosome entry site (IRES)-dependent translation during the early phases of infection before provirus integration. Our results document the critical role of TIM-TAM in Tat expression to facilitate virus reactivation from latency, with implications for HIV treatment and drug development.
A N7-guanine RNA cap methyltransferase signature-sequence as a genetic marker of large genome, non-mammalian Tobaniviridae
Authors: Ferron François , Debat Humberto J , Shannon Ashleigh , Decroly Etienne , Canard Bruno
Published: December 2019

The order Nidovirales is a diverse group of (+)RNA viruses, classified together based on their common genome organisation and conserved replicative enzymes, despite drastic differences in size and complexity. One such difference pertains to the mechanisms and enzymes responsible for generation of the proposed viral 5′ RNA cap. Within the Coronaviridae family, two separate methytransferases (MTase), nsp14 and nsp16, perform the RNA-cap N7-guanine and 2′-OH methylation respectively for generation of the proposed m7GpppNm type I cap structure. For the majority of other families within the Nidovirales order, the presence, structure and key enzymes involved in 5′ capping are far less clear. These viruses either lack completely an RNA MTase signature sequence, or lack an N7-guanine methyltransferase signature sequence, obscuring our understanding about how RNA-caps are N7-methylated for these families. Here, we report the discovery of a putative Rossmann fold RNA methyltransferase in 10 Tobaniviridae members in Orf1a, an unusual genome locus for this gene. Multiple sequence alignments and structural analyses lead us to propose this novel gene as a typical RNA-cap N7-guanine MTase with substrate specificity and active-site organization similar to the canonical eukaryotic RNA-cap N7-guanine MTase.
Focused Ultrasound Strategies for Brain Tumor Therapy
Authors: Bunevicius Adomas , McDannold Nathan Judson , Golby Alexandra J
Published: December 2019

BACKGROUND

A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood–brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors.

OBJECTIVE

To review the mechanism of FUS, preclinical evidence, and clinical studies that used low-frequency FUS for a BBB opening in gliomas.

METHODS

Literature review.

RESULTS

The potential of externally delivered low-intensity ultrasound for a temporally and spatially precise and predictable disruption of the BBB has been investigated for over a decade, yielding extensive preclinical literature demonstrating that FUS can disrupt the BBB in a spatially targeted and temporally reversible manner. Studies in animal models documented that FUS enhanced the delivery of numerous chemotherapeutic and investigational agents across the BBB and into brain tumors, including temozolomide, bevacizumab, 1,3-bis (2-chloroethyl)-1-nitrosourea, doxorubicin, viral vectors, and cells. Chemotherapeutic interventions combined with FUS slowed tumor progression and improved animal survival. Recent advances of MRgFUS systems allow precise, temporally and spatially controllable, and safe transcranial delivery of ultrasound energy. Initial clinical evidence in glioma patients has shown the efficacy of MRgFUS in disrupting the BBB, as demonstrated by an enhanced gadolinium penetration.

CONCLUSION

Thus far, a temporary disruption of the BBB followed by the administration of chemotherapy has been both feasible and safe. Further studies are needed to determine the actual drug delivery, including the drug distribution at a tissue-level scale, as well as effects on tumor growth and patient prognosis.
Anscombe's Intention
Authors: Schwenkler John
Published: December 2019

This book provides a careful, critical, and appropriately contextualized presentation of the main lines of argument in G.E.M. Anscombe’s seminal book, Intention, at a level appropriate to the advanced undergraduate but also capable of benefiting specialists in action theory, ethics, and the history of analytic philosophy. It begins by situating Anscombe’s project in relation to the controversy she initiated over the decision by the University of Oxford to award an honorary degree to Harry Truman, and the connection she saw between her Oxford colleagues’ willingness to excuse Truman’s murderous actions and the situation of moral philosophy at the time. It also documents many of the ways Anscombe drew on the thought of Aristotle, Aquinas, and Wittgenstein, as well as the points at which her argument engages with the work of then-contemporary authors, especially R.M. Hare and Gilbert Ryle. Against this background, the primary focus of the book is on presenting Anscombe’s arguments and assessing the plausibility and philosophical power of the position she develops. Topics that receive especially close attention include: Anscombe’s argument that the primary role of the concept of intention is in the description of what happens in the world, and not of an agent’s state of mind; her account of action as a teleological unity; the relation between rationalizing explanation and causal explanation; the difference between practical and theoretical reasoning; and the possibility of non-observational self-knowledge of what one intentionally does.
Knowledge without Observation
Authors: Schwenkler John
Published: December 2019

This chapter discusses the argument of Sections 28–32 of G.E.M. Anscombe’s Intention. It begins by relating Anscombe’s thesis that intentional action is known without observation to Wittgenstein’s discussion in the Blue Book of the knowledge of oneself “as subject” and Anscombe’s discussion in “The First Person” of unmediated self-knowledge. Following this, the chapter explores the difficulties that herself Anscombe raises for her thesis, and considers her reasons for thinking that the scope of an agent’s non-observational self-knowledge is not limited to her interior states or immediate bodily movements. Finally, it considers how the difficulties that Anscombe has raised are supposed to be addressed by her discussion of how descriptions of one’s intentional action can be contradicted, and of the difference between a list that has the role of an order and one whose role is to provide an accurate description of some facts.
Touching Figures
Authors: Marchal Joseph A.
Published: December 2019

Chapter 1 further situates queer approaches to history and temporality as a way forward and out of persistent debates about whether and how the past is different from the present. These debates have been of particular interest in the study of gender and sexuality in the ancient Greco-Roman world. This project charts and performs a third way of approaching figures from the past, presenting options beyond a stress on identity or alterity, as positioned by scholars of ancient materials like Bernadette Brooten and David Halperin. Queer thinkers focused on other premodern periods provide insights for this approach, particularly Carolyn Dinshaw’s conceptualization of “touches across time.” Inspired by this approach, each of the following chapters is structured by a specific anachronistic juxtaposition that provides an alternative angle on those who have been marginalized and vilified in both the past and the present.
The Color Spectrum Exercise
Authors: Azize Joseph
Published: December 2019

This exercise was taught by George Adie. It is almost certainly an otherwise unknown example of Gurdjieff’s Transformed-contemplation. The theoretical basis for it is evident in Gurdjieff’s writings, especially in the final chapter of his Life Is Real, Only Then, When “I Am.” There it was said that the vibrations given off by one’s presence in a state of relaxation form a sort of atmosphere which was “analogous to the spectrum of colors.” That atmosphere is said to alter as soon as a person starts to think, feel or move. The exercise as taught to Adie was given as a practice for strengthening one’s sense of being, reality, and presence, by sensing the body with the aid of the visualization of colors suffusing different parts of the body in a given sequence, and finally adding consciousness of the breath. At the very least, it aims to strengthen one’s sense of the vibrations of one’s presence.
Material Monism and Bodily Parts
Authors: Schmaltz Tad M.
Published: December 2019

This chapter addresses the question of whether Spinoza’s reference to finite bodies as “parts” that compose an infinite material nature is compatible with the implication of his monism that extended substance is indivisible. There is particular emphasis on the distinctively Spinozistic notion of a “modal part.” It is argued that though Spinoza requires that substantial quantity is indivisible, he holds that quantity can also be conceived to be a modal whole that is divisible into modal parts. The account of this latter sort of quantity is related to Spinoza’s view that nature as a whole can be considered to be an infinite mode that is itself an “individual” that comprises all finite bodily individuals as its parts. The chapter closes with a consideration of the implication of Spinoza’s mereology that the relation of parts to the wholes they compose is weaker than the relation of modes to what they modify.
Emotions as Axiological Information
Authors: Andrew Youpa
Published: December 2019

This chapter argues that because emotions symptomatically represent changes in power, emotions carry information about the status of an individual’s power. Emotions, in Spinoza’s view, carry axiological information. Emotive information is “axiological” in the sense that it is information about the goodness and badness of the state of an individual’s power of acting. Increases in power and decreases in power are not psychologically and ethically equal. It is not the case that an increase in an individual’s power is psychologically and ethically no better and no worse than a decrease in power. On the contrary, an increase in power in part of an individual is, other things equal, better than a decrease in power, and an increase in power as a whole is invariably better than a decrease in power. The author also argues that, for Spinoza, increases and decreases in power are not psychologically and ethically neutral or indifferent. An increase in an individual’s power as a whole is a genuine enhancement of his nature, whereas a decrease in power as a whole is a genuine impairment of his nature.
Underivative Goodness and Underivative Badness
Authors: Andrew Youpa
Published: December 2019

Having examined the foundation of Spinoza’s moral philosophy in the previous four chapters, in this chapter the author begins to flesh out Spinoza’s moral philosophy. He argues that Spinoza is committed to the underivative goodness of human wellness and the underivative badness of human illness. He shows that such goodness is naturalistic in a sense that makes it a precursor to contemporary sciences that deal with physical and mental health. And he elaborates the specific type of axiological ambiguity and complexity to which Spinoza’s naturalism leads by outlining his hierarchical system of classification of emotions, a hierarchy based on whether a type of emotion is indefeasibly good, defeasibly good, indefeasibly bad, or defeasibly bad. This system of classification, in turn, undergirds the classification of desires as indefeasibly good, defeasibly good, indefeasibly bad, or defeasibly bad.
The Empowered Life: Nobility
Authors: Andrew Youpa
Published: December 2019

The person of Spinozistic fortitudo takes intelligent care of himself, which is to possess the virtue of tenacity, and he takes intelligent care of others, which is to possess the virtue of nobility. The person of fortitudo is a friend to himself and he is a friend to others. This chapter examines Spinoza’s theory of nobility and the central role of friendship in his conception of the empowered life. The author argues that nobility is a distinct type of love. Nobility is empowered love. Essential to empowered love is the desire to help and befriend others, and he shows that helping others is about empowering others to live joyously and lovingly. The most important way to help others to live in this way is through education. Moreover, education, in Spinoza’s view, is a social project, and the author highlights three ways that it is social. Finally, the chapter shows how Spinozistic friendship and the virtue of courtesy (modestia) prepare us for a life of learning.