bluuebunny/crossref_metadata_2025 huggingface dataset:
Defects of roofing and roof structure – Apartment house Kaplice
Authors: Dedic Martin
Published: September 2019

The aim of this paper is to provide information on the defects of roofing and roof structure on the Apartment house Kaplice. The roof cover is Beronit fiber-cement template cover and the roof template is 400 x 400 mm (square with corrugated corners). The roof was laid according to the design documentation and documented invoices 10 years ago. The roof as a whole, as a result of very serious defects, does not fulfill its function (protection of the object from weathering). The rainwater penetrates into the attic and affects the wooden elements of the roof structure. Wooden elements of truss construction, in particular, formwork and rafters, in the ridge area, are infested with mold. The Czech Mycological Society confirmed the attack of wood mold elements, testing the samples taken. One sample from the inside face of the roof formwork has higher mold values, and the other sample has even high mold values. The attic space can only be ventilated through the opening windows and the roofing is designed as unpaved. During the ten-year lifetime of the roofing, one repair was carried out, which further aggravated the condition. The detected state of the roof is an emergency and the implemented measure in the form of capturing penetrated water into plastic containers is not enough to stop the deepening of destructive roof processes. Temporary repairs to roof roofing did not benefit, and on the contrary, it is one of the main factors causing cracking and shading of the roofing patterns and thus the penetration of rainwater into the soil.
Hydraulic Stabilization of Heat Network
Authors: Bukowska Maria , Nowak Krzysztof
Published: September 2019

The article analyzes changes in pressure in the heating network taking into account the variable daily heat consumption. The simulation assumes diversification of heat demand during the day due to significant differences in the distribution of hot water. Taking the decreases in hot water consumption by up to 70%, pressure losses were calculated on the sections of the district heating network. Changes in the flow rate are taken into account. The simulation assumed changes in water flow from 10% to 70% respectively. Completed calculations and results are presented in diagrams drawn up for different amounts of hot water consumption. They allowed determining the size of the changing pressure of the available heat network. Graphs of dependencies between changing flows and the corresponding pressure values illustrate the magnitude of these changes. In the case of central heating, the heat demand is determined in the so-called external air temperature calculation conditions. The heating plant works in accordance with an ordered diagram of heat loads. The amount of heat delivered to the recipient for central heating depends on the outside temperature. It is calculated on the basis of the heat load factor and the average heat demand of individual customers. In relation to the production of hot water, the unevenness of the hot water demand should be taken into account. This variable size, as a result of the day, is described by the hourly diversity factor. For such calculations, daily schedules of hot water consumption are developed. On their basis, the operation of the heat network was analyzed. The heating network section and the hydraulic system of the network were analyzed for existing pressure changes, which are caused by the variability of the heat demand for heating domestic hot water. The calculations and simulations carried out show that the calculated flows, and thus also the pressure losses in the considered network, are variable and depend on the distribution of hot water to consumers. These differences are significant and affect the choice of pumps, which can bring significant financial benefits throughout the year.
The use of forest waste in the energy sector
Authors: Proszak-Miasik Danuta , Rabczak Slawomir
Published: September 2019

Forest areas cover almost 30% of the territory of Poland, of which about 70% are coniferous forests, the rest are deciduous and mixed forests. Annually, about 9, 000 trees are cut from these areas, which give about 36 km2 of wood. Analyzing we can assume that we will obtain 10m3 of bark, 15m3 of brushwood, 20m3 of branch and carpinus, 19 m3 of sawdust and 36m3 of sawn timber from 100m3 of wood obtained in the forest. Wood obtained from forest areas is used not only as one of the main construction and industrial materials, but also as an energy raw material. For energetic wood, we include all forms of biomass obtained directly from the forest felling: needles, leaves, carpels, bark, branches, sawdust, shavings, cones and from recovery, crates, pallets, sleepers. The calorific value of the collected samples was examined. As a fuel, it can be used the wood biomass that has not been processed in the form of firewood or fuel, or processed in the form of sawdust, wood chips, briquettes, pellets or wood dust. This publication shows the combustion process of fuel obtained from wood biomass. Factors that influence the calorific value obtained and the value of the heat of combustion are described. The paper presents the results obtained from the incineration of waste obtained from forest areas. The study uses cones and sawdust obtained from the following tree species: fir, poplar, birch and beech. The influence of moisture content in wood as the main factor influencing the calorific value of fuel was also discussed.
Use of technical hemp for concrete - Hempcrete
Authors: Novakova Petra , Sal Jiri
Published: September 2019

We live at the time of trying to reduce the carbon footprint, which also involves the production of building insulation. Today’s trend is the construction of passive houses with the best insulation and reduced heating costs. By reducing the incineration of non-renewable sources for heating, we will reduce the carbon footprint, but by increasing the classical building thermal insulation, whether based on plastics or minerals. A suitable option is natural materials. This article deals with the use of technical hemp in concrete. Hemp is a historically widely used plant, but its decline has occurred due to its similarity to the THC variety, so this plant is now more known for its narcotic effects. For use in construction, industry, etc., the Cannabis Sativa L. variety, so-called Technical Hemp with negligible THC content, is used. Today, the use of technical cannabis is rediscovered. By adding technical hemp to the concrete, we improve the thermal properties of the concrete to the detriment of strength properties. The article describes different properties of the hemp concrete compared to the conventional concrete. In the building construction industry, it is known for the use in the cannabis insulation, hemp concrete, hemp oils and varnishes, Honeycomb plaster, ropes and strands. The best known are the cannabis insulation in the form of mats and hemp ropes, but there is also a widespread use of cannabis, which is discussed in this article. By measuring, the compressive strengths of the cannulated concrete were 1.13 MPa, which is comparable to that of the lightweight concrete and foam concrete. From this finding, that hemp concrete can be used as a filler material, nickels as a carrier material. This concrete can be used as a binder, both hydraulic lime and cement. However, when using cement, it is necessary to mineralize the shaker, which is a laborious and long-lasting activity.
Environmental use of waste materials as admixtures in concrete
Authors: Novotny Radimir , Sal Jiri , Ctibor Marek
Published: September 2019

Humanity, from prehistoric times, influences the environment in which it lives. Often these are unfortunate negative influences. One of such negative effects is the accumulation of waste. We are an animal species that has always left a lot of waste, food remnants, various tools, remnants of producing these tools, and much more. First, the mankind used resources from which the waste was minimal and which was moreover degradable. As a result of the development of the company, the need for better, more perfect products developed and hand in hand is associated with more waste and non-decomposable or non-decomposable waste. The more humanity is at the higher level of development, the more waste it produces. However, this behavior conflicts with the sustainability of the environment. Fortunately, they are making bigger efforts to recycle the waste, ie re-use of waste materials. Construction is not behind this, and many efforts are being made to use the waste materials in building structures. The best known is the recycling of glass for the production of window glass, for example, but there are many examples. Glass has exceptional properties in this respect because it can be recycled to the infinity. For many substances, it is not possible to find a use other than their primary use. In this article, we are focusing on the re-use of various waste materials as admixtures in concrete. The use of waste materials in concrete is directly available, not only because of the number of concrete structures, but also because of the closure of waste materials in its structure. Some waste materials can be used as fillers, that is to say, substitute aggregates, but they are substances which can also be used as a replacement for a part of a binder, in this case, of cement. The article summarizes the existing use of waste materials in concrete and provides a space for possible detailed research on this concrete.
Effective lambda-proton and lambda-neutron potentials from subthreshold inverse scattering
Authors: Meoto E F , Lekala M L
Published: September 2019

Potentials are constructed for the lambda-nucleon interaction in the

1

S

0

and

3

S

1

channels. These potentials are recovered from scattering phases below the inelastic threshold through Gel’fand-Levitan-Marchenko theory. Experimental data with good statistics is not available for lambda-nucleon scattering. This leaves theoretical scattering phases as the only option through which the rigorous theory of quantum inverse scattering can be used in probing the lambda-nucleon force. Using rational-function interpolations on the theoretical scattering data, the kernels of the Gel’fand-Levitan-Marchenko integral equation become degenerate, resulting in a closed-form solution. The new potentials restored, which are shown to be unique through the Levinson theorem, bear the expected features of short-range repulsion and intermediate-range attraction. Charge symmetry breaking, which is perceptible in the scattering phases, is preserved in the new potentials. The lambda-nucleon force in the

1

S

0

channel is observed to be stronger than in the

3

S

1

channel, as expected. In addition, the potentials bear certain distinctive features whose effects on hypernuclear systems can be explored through Schrödinger calculations.
Green space suitability evaluation for urban resilience: an analysis of Kathmandu Metropolitan city, Nepal
Authors: Pokhrel Shiva
Published: September 2019

Unplanned urbanization, demographic and environmental changes have forced many cities into more uncertainty and risk, challenging economic, social, and environmental sustainability. In this context nurturing resilience in the face of various uncertainties of environmental, socioeconomic and other sociopolitical risk is an urgent matter. Resilience has become an important goal for many cities throughout the world leading to the enhancement of urban ecology and maintenance of essential ecosystem goods and services to make sure the sustainable future for all. The Kathmandu metropolitan city is one of the fastest-growing capital cities with recent and frequent evidence of unplanned development, loss of green space, tragic events of an earthquake, flood and other environmental problems causing devastation, economic damages, and loss of human life/health, and habitats. In this background, the paper evaluates suitable sites for urban green space development using the analytical hierarchy process (AHP) based multi-criteria analysis methods with geographical information system (GIS).Variables taken for this study are school point data, health facility’s location data, emergency service’s locations, water bodies, emergency road network data, recent land use/land cover data, population data, existing park, and slope. The unit of a study is a metropolitan city. Our evaluations demonstrate the spatial distribution of different not suitable areas, less suitable, moderate suitable, and highly suitable area respectively, of the 4.47%, 7.19% of the area are high and moderate suitable area, while the largest area 78.87% is less suitable and 9.47% are not suitable for the development of green open space. The result indicates human occupancy is everywhere and per capita, open green space in the city is very below the global average. The local government must think about different modality for development of green open space in collaboration with other government agency occupying more open space or engagement with private sectors. This finding could contribute a planner for spatial planning of green space development in a Metropolitan City.
Copeptin Levels in Patients With Treatment-Resistant Hypertension Before and 6 Months After Renal Denervation
Authors: Bosch Agnes , Schmid Axel , Ott Christian , Kannenkeril Dennis , Karg Marina V , Ditting Tilmann , Veelken Roland , Uder Michael , Schmieder Roland E
Published: September 2019

BACKGROUND

Copeptin, the C-terminal peptide of provasopressin, is released from the neurohypophysis and reflects the activity of the hormone arginine vasopressin in patients with hypertension. Elevated copeptin levels are associated with increased cardiovascular and all-cause mortality. The aim of this study is to compare copeptin levels in patients with treatment-resistant hypertension (TRH) before and 6 months after renal denervation (RDN).

METHODS

Copeptin was measured in 34 patients with TRH and 30 patients with primary hypertension stage 1 or 2 (HT). In addition, copeptin levels were measured in patients with TRH at 6-month follow-up visit after RDN. RDN was performed by an experienced interventionalist applying at least 4 ablations longitudinally and rotationally within the lengths of each renal artery to cover a full 4-quadrant ablation.

RESULTS

In patients with TRH 24-hour ambulatory blood pressure (BP) decreased from 154 ± 15/87 ± 12 mm Hg to 146 ± 13/83 ± 7.9 mm Hg after RDN (systolic: P = 0.001, diastolic: P = 0.034). There was no significant change in copeptin levels in these 34 patients with TRH before vs. 6 months after RDN (median 8.4 [interquartile range 3.6–14] vs. 8.5 [4.5–13] pmol/l, P = 0.334). Patients with TRH had higher copeptin levels (P = 0.024) than patients with HT (24-hour ambulatory BP: 142 ± 11/91 ± 8.3 mm Hg, copeptin: 4.2 [2.8–6.3] pmol/l).

CONCLUSION

Patients with TRH showed 2-fold higher copeptin levels than patients with HT. RDN did not lead to any change of copeptin levels in patients with TRH 6 months after procedure despite significant fall in BP.

CLINICAL TRIAL REGISTRATION

NCT01318395, NCT01687725
Aliskiren and the dual complement inhibition concept
Authors: Perez-Gomez Maria Vanessa , Ortiz Alberto
Published: September 2019

In this issue of Clinical Kidney Journal, Plasse et al. report on the use of high-dose aliskiren as an adjunct therapy in a patient treated with eculizumab for haemolytic uraemic syndrome (HUS). This follows the recent description of the complement factor 3 (C3) activating activity of the enzyme renin and the successful therapeutic use of the direct renin inhibitor aliskiren in three cases of C3 glomerulopathy/dense deposit disease. We discuss the potential clinical and pathophysiological implications of these reports on nephropathies linked to complement, from HUS to C3 glomerulopathy to immunoglobulin A nephropathy as well as the concept of dual complement inhibition for kidney disease.
Strong Purifying Selection Is Associated with Genome Streamlining in Epipelagic Marinimicrobia
Authors: Martinez-Gutierrez Carolina Alejandra , Aylward Frank O
Published: September 2019

Marine microorganisms inhabiting nutrient-depleted waters play critical roles in global biogeochemical cycles due to their abundance and broad distribution. Many of these microbes share similar genomic features including small genome size, low % G + C content, short intergenic regions, and low nitrogen content in encoded amino acid residue side chains (N-ARSC), but the evolutionary drivers of these characteristics are unclear. Here, we compared the strength of purifying selection across the Marinimicrobia, a candidate phylum which encompasses a broad range of phylogenetic groups with disparate genomic features, by estimating the ratio of nonsynonymous and synonymous substitutions (dN/dS) in conserved marker genes. Our analysis reveals that epipelagic Marinimicrobia that exhibit features consistent with genome streamlining have significantly lower dN/dS values when compared with their mesopelagic counterparts. We also found a significant positive correlation between median dN/dS values and % G + C content, N-ARSC, and intergenic region length. We did not identify a significant correlation between dN/dS ratios and estimated genome size, suggesting the strength of selection is not a primary factor shaping genome size in this group. Our findings are generally consistent with genome streamlining theory, which postulates that many genomic features of abundant epipelagic bacteria are the result of adaptation to oligotrophic nutrient conditions. Our results are also in agreement with previous findings that genome streamlining is common in epipelagic waters, suggesting that microbes inhabiting this region of the ocean have been shaped by strong selection together with prevalent nutritional constraints characteristic of this environment.
Simulation of elastic wave propagation across fractures using a nodal discontinuous Galerkin method—theory, implementation and validation
Authors: Möller T , Friederich W
Published: September 2019

An existing nodal discontinuous Galerkin (NDG) method for the simulation of seismic waves in heterogeneous media is extended to media containing fractures with various rheological behaviour. Fractures are treated as 2-D surfaces where Schoenberg’s linear slip or displacement discontinuity condition is applied as an additional boundary condition to the elastic wave equation which is in turn implemented as an additional numerical flux within the NDG formulation. Explicit expressions for the new numerical flux are derived by considering the Riemann problem for the elastic wave equation at fractures with varying rheologies. In all cases, we obtain further first order differential equations that fully describe the temporal evolution of the particle velocity jump at the fracture. Our flux formulation allows to separate the effect of a fracture from flux contributions due to simple welded interfaces enabling us to easily declare element faces as parts of a fracture. We make use of this fact by first generating the numerical mesh and then building up fractures by selecting appropriate element faces instead of adjusting the mesh to pre-defined fracture surfaces. The implementation of the new numerical fluxes into NDG is verified in 1-D by comparison to an analytical solution and in 2-D by comparing the results of a simulation valid in 1-D and 2-D. Further numerical examples address the effect of fracture systems on seismic wave propagation in 1-D and 2-D featuring effective anisotropy and coda generation. Finally, a study of the reflective and transmissive behaviour of fractures indicates that reflection and transmission coefficients are controlled by the ratio of signal frequency and relaxation frequency of the fracture.
Inference of unexploded ordnance (UXO) by probabilistic inversion of magnetic data
Authors: Wigh Mark David , Hansen Thomas Mejer , Døssing Arne
Published: September 2019

Magnetic modelling of unexploded ordnance (UXO) is a well-documented method used to interpret magnetic anomalies occurring in UXO excavation surveys. By treating UXO as a ferrous spheroidal object, the induced dipole moment can be estimated by approximation of UXO characteristics such as shape, size and orientation. Inversion of magnetic data with respect to UXO requires one to solve the equation for the induced dipole moment, while also determining the location and orientation of the object. This is a highly nonlinear, non-unique problem, where many solutions often are present, which make it difficult for standard inversion methods, such as linearized approaches and maximum likelihood estimators, in assessing uncertainties and correlations in estimated model parameters that often result in an incomplete solution. In this study, we treat the problem concerning magnetic UXO inversion by a probabilistic approach using Markov chain Monte Carlo (McMC) sampling. To deal with the potential multimodality, a combination of two well-known McMC sampling methods is employed in a single-chain approach: the extended Metropolis algorithm is used for efficient local sampling, and the Gibbs sampler is used to help exploring the possible multimodal density of the posterior. By adding a Gibbs step we significantly increase the efficiency of the extended Metropolis, making it viable to use as a single-chain sampler for this problem. We refer to the algorithm as the Gibbs-within-Metropolis algorithm. We test and compare the proposed algorithm to a multichain McMC parallel tempering setup using the extended Metropolis algorithm. We then present synthetic cases and a real data case, where the algorithm is used. We demonstrate how the probabilistic approach allows full inference of the parameters describing a UXO while also including the possible presence of remanent magnetization.
Functional assessment of variants associated with Wolfram syndrome
Authors: Riachi Melissa , Yilmaz Sebahat , Kurnaz Erdal , Aycan Zehra , Çetinkaya Semra , Tranebjærg Lisbeth , Rendtorff Nanna Dahl , Bitner-Glindzicz Maria , Bockenhauer Detlef , Hussain Khalid
Published: September 2019

Wolfram syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and neurological complications in combination or in isolation. To date, the understanding of the genotype-phenotype relationship in this complex syndrome remains poorly understood. In this study, we identified and explored the functionality of rare and novel variants in the two causative WS genes WFS1 and CISD2 by assessing the effects of the mutations on the encoded proteins Wolframin and ERIS, in a cohort of 12 patients with autosomal recessive WS, dominant WS and WS type 2. The identified pathogenic variants included missense changes, frameshift deletions and insertions in WFS1 and an exonic deletion in CISD2 which all altered the respective encoded protein in a manner that did not correlate to the phenome previously described. These observations suggest the lack of genotype-phenotype correlation in this complex syndrome and the need to explore other molecular genetic mechanisms. Additionally, our findings highlight the importance of functionally assessing variants for their pathogenicity to tackle the problem of increasing variants of unknown significance in the public genetic databases.
Light-induced stress as a primary evolutionary driver of eye origins
Authors: Swafford Andrew J M , Oakley Todd H
Published: September 2019

Eyes are quintessential complex traits and our understanding of their evolution guides models of trait evolution in general. A long-standing account of eye evolution argues natural selection favors morphological variations that allow increased functionality for sensing light. While certainly true in part, this focus on visual performance does not entirely explain why diffuse photosensitivity persists even after eyes evolve, or why eyes evolved many times, each time using similar building blocks. Here, we briefly review a vast literature indicating most genetic components of eyes historically responded to stress caused directly by light, including ultraviolet damage of DNA, oxidative stress, and production of aldehydes. We propose light-induced stress had a direct and prominent role in the evolution of eyes by bringing together genes to repair and prevent damage from light-stress, both before and during the evolution of eyes themselves. Stress-repair and stress-prevention genes were perhaps originally deployed as plastic responses to light and/or as beneficial mutations genetically driving expression where light was prominent. These stress-response genes sense, shield, and refract light but only as reactions to ongoing light stress. Once under regulatory-genetic control, they could be expressed before light stress appeared, evolve as a module, and be influenced by natural selection to increase functionality for sensing light, ultimately leading to complex eyes and behaviors. Recognizing the potentially prominent role of stress in eye evolution invites discussions of plasticity and assimilation and provides a hypothesis for why similar genes are repeatedly used in convergent eyes. Broadening the drivers of eye evolution encourages consideration of multi-faceted mechanisms of plasticity/assimilation and mutation/selection for complex novelties and innovations in general.
Boolean Product Polynomials, Schur Positivity, and Chern Plethysm
Authors: Billey Sara C , Rhoades Brendon , Tewari Vasu
Published: September 2019

Let $k \leq n$ be positive integers, and let $X_n = (x_1, \dots , x_n)$ be a list of $n$ variables. The Boolean product polynomial  $B_{n,k}(X_n)$ is the product of the linear forms $\sum _{i \in S} x_i$, where $S$ ranges over all $k$-element subsets of $\{1, 2, \dots , n\}$. We prove that Boolean product polynomials are Schur positive. We do this via a new method of proving Schur positivity using vector bundles and a symmetric function operation we call Chern plethysm. This gives a geometric method for producing a vast array of Schur positive polynomials whose Schur positivity lacks (at present) a combinatorial or representation theoretic proof. We relate the polynomials $B_{n,k}(X_n)$ for certain $k$ to other combinatorial objects including derangements, positroids, alternating sign matrices, and reverse flagged fillings of a partition shape. We also relate $B_{n,n-1}(X_n)$ to a bigraded action of the symmetric group ${\mathfrak{S}}_n$ on a divergence free quotient of superspace.
Prevalence, Incidence, and Clearance of Human Papillomavirus Types Covered by Current Vaccines in Men With Human Immunodeficiency Virus in the SUN Study
Authors: Patel Pragna , Bush Tim , Conley Lois , Unger Elizabeth R , Darragh Teresa M , Henry Keith , Escota Gerome , Brooks John T , Kojic Erna Milunka
Published: September 2019

Background

High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized.

Methods

We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact.

Results

Baseline prevalence of any anal 9v HR-HPV type among men who have sex with men (MSM) and men who have sex with women (MSW) was 74% and 25% (P < .001), respectively. Among 299 MSM, abnormal cytology was detected in 161 (54%) MSM and was associated with the presence of any 9v HR-HPV (relative risk [RR], 1.8 [95% confidence interval {CI}, 1.3–2.6]; P < .001). Among 61 MSW, abnormal anal cytology was detected in 12 (20%) and was associated with the presence of any 9v HR-HPV (RR, 4.3 [95% CI, 1.6–11.5]; P < .001).

Conclusions

Among men with HIV, the prevalence of the 7 HR-HPV types in the 9v vaccine was high and was associated with abnormal cytology. These findings indicate that men with HIV could benefit from prophylactic administration of the 9v HPV vaccine.
A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress
Authors: Di Liddo Antonella , de Oliveira Freitas Machado Camila , Fischer Sandra , Ebersberger Stefanie , Heumüller Andreas W , Weigand Julia E , Müller-McNicoll Michaela , Zarnack Kathi
Published: September 2019

Hypoxia is associated with several diseases, including cancer. Cells that are deprived of adequate oxygen supply trigger transcriptional and post-transcriptional responses, which control cellular pathways such as angiogenesis, proliferation, and metabolic adaptation. Circular RNAs (circRNAs) are a novel class of mainly non-coding RNAs, which have been implicated in multiple cancers and attract increasing attention as potential biomarkers. Here, we characterize the circRNA signatures of three different cancer cell lines from cervical (HeLa), breast (MCF-7), and lung (A549) cancer under hypoxia. In order to reliably detect circRNAs, we integrate available tools with custom approaches for quantification and statistical analysis. Using this consolidated computational pipeline, we identify ~12000 circRNAs in the three cancer cell lines. Their molecular characteristics point to an involvement of complementary RNA sequences as well as trans-acting factors in circRNA biogenesis, such as the RNA-binding protein HNRNPC. Notably, we detect a number of circRNAs that are more abundant than their linear counterparts. In addition, 64 circRNAs significantly change in abundance upon hypoxia, in most cases in a cell type-specific manner. In summary, we present a comparative circRNA profiling in human cancer cell lines, which promises novel insights into the biogenesis and function of circRNAs under hypoxic stress.
Single-Arm Phase II Trials of Combination Therapies: A Review of the CTEP Experience 2008–2017
Authors: Foster Jared C , Freidlin Boris , Kunos Charles A , Korn Edward L
Published: September 2019

Designing and interpreting single-arm phase II trials of combinations of agents is challenging because it can be difficult, based on historical data, to identify levels of activity for which the combination would be worth pursuing. We identified Cancer Therapy Evaluation Program single-arm combination trials that were activated in 2008–2017 and tabulated their design characteristics and results. Positive trials were evaluated as to whether they provided credible evidence that the combination was better than its constituents. A total of 125 trials were identified, and 120 trials had results available. Twelve had designs where eligible patients were required to be resistant or refractory to all but one element of the combination. Only 17.8% of the 45 positive trials were deemed to provide credible evidence that the combination was better than its constituents. Of the 10 positive trials with observed rates 10 percentage points higher than their upper (alternative hypothesis) targets, only five were deemed to provide such credible evidence. Many trials were definitively negative, with observed clinical activity at or below their lower (null hypothesis) targets. Ideally, use of single-arm combination trials should be restricted to settings where each agent is known to have minimal monotherapy activity (and a randomized trial is infeasible). In these settings, an observed signal is attributable to synergy and thus could be used to decide whether the combination is worth pursuing. In other settings, credible evidence can still be obtained if the observed activity is much higher than expected, but experience suggests that this is a rare occurrence.
Alterations in GABAA Receptor Subunit Expression in the Amygdala and Entorhinal Cortex in Human Temporal Lobe Epilepsy
Authors: Stefanits Harald , Milenkovic Ivan , Mahr Nina , Pataraia Ekaterina , Baumgartner Christoph , Hainfellner Johannes A , Kovacs Gabor G , Kasprian Gregor , Sieghart Werner , Yilmazer-Hanke Deniz , Czech Thomas
Published: September 2019

The amygdala has long been implicated in the pathophysiology of human temporal lobe epilepsy (TLE). The different nuclei of this complex structure are interconnected and share reciprocal connections with the hippocampus and other brain structures, partly via the entorhinal cortex. Expression of GABAA receptor subunits α1, α2, α3, α5, β2, β2/3, and γ2 was evaluated by immunohistochemistry in amygdala specimens and the entorhinal cortex of 12 TLE patients and 12 autopsy controls. A substantial decrease in the expression of α1, α2, α3, and β2/3 subunits was found in TLE cases, accompanied by an increase of γ2 subunit expression in many nuclei. In the entorhinal cortex, the expression of all GABAA receptor subunits was decreased except for the α1 subunit, which was increased on cellular somata. The overall reduction in α subunit expression may lead to decreased sensitivity to GABA and its ligands and compromise phasic inhibition, whereas upregulation of the γ2 subunit might influence clustering and kinetics of receptors and impair tonic inhibition. The description of these alterations in the human amygdala is important for the understanding of network changes in TLE as well as the development of subunit-specific therapeutic agents for the treatment of this disease.
THE EFFECTS OF BROADCASTING DIGITIZATION ON EU COMPETITION LAW: A TALE OF EU COPYRIGHT POLICIES
Authors: Bania Konstantina
Published: September 2019

In recent years, buzz terms such as “geo-blocking”, “online content portability”, and “digital copyright” have been making rounds in EU policy circles. This is largely attributed to the “Digital Single Market Strategy”, an ambitious reform the objective of which is to ensure seamless cross-border access to online services. Pursuit of this objective appears to be largely driven by the assumption that limiting the exclusivity of copyright would stimulate intra-Union competition in content markets. Against the background of EU competence limitations in the field of copyright and the increasing popularity of global U.S. firms in European audiovisual markets, this paper argues that EU Competition Law has vainly been instrumentalized to complete a single market for content. More particularly, based on legal and policy developments, which appear to challenge widespread licensing practices, sector-specific economics, and the case law that sets the conditions under which competition enforcement may introduce limits to copyright protection, this study develops the following twofold argument: in an attempt to create a single market for copyright-protected broadcast content, the EU has stretched the boundaries of competition law in an excessive manner and such unjustified interference with copyright is simply inadequate to promote competition and market integration.
Regulation of flowering transition by alternative splicing: the role of the U2 auxiliary factor
Authors: Wang Yu-Yi , Xiong Feng , Ren Qiu-Ping , Wang Xiu-Ling
Published: September 2019

AtU2AF65a and AtU2AF65b encode the large subunit of the U2AF complex and mediate the splicing of key flowering genes to control flowering transition in response to ambient temperature and ABA signaling.
eROSITA detection rates for tidal disruptions of white dwarfs by intermediate mass black holes
Authors: Malyali A , Rau A , Nandra K
Published: September 2019

White dwarf black hole tidal disruption events (herein WTDEs) present an opportunity to probe the quiescent intermediate mass black hole population in the Universe. We run an extensive set of Monte Carlo based simulations to explore SRG/eROSITA’s detection sensitivity to WTDEs as a function of black hole mass, redshift, and time offset between event flaring and it first being observed. A novel estimate of WTDE rate densities from globular clusters and dwarf galaxies is also presented. We combine this with estimated detection sensitivities to infer the rate of eROSITA detecting these events. Depending on the estimate of the intrinsic rate of WTDEs, we anticipate that eROSITA may detect three events over its 4 yr all-sky survey. eROSITA will be most sensitive to systems with black hole masses above $10^4\, \mathrm{M}_{\odot }$, and is most likely to catch these within 5 d of flaring.
Non–adiabatic tidal oscillations induced by a planetary companion
Authors: Bunting Andrew , Papaloizou John C B , Terquem Caroline
Published: September 2019

We calculate the dynamical tides raised by a close planetary companion on non–rotating stars of 1 M⊙ and 1.4 M⊙. Using the Henyey method, we solve the fully non–adiabatic equations throughout the star. The horizontal Lagrangian displacement is found to be 10 to 100 times larger than the equilibrium tide value in a thin region near the surface of the star. This is because non–adiabatic effects dominate in a region that extends from below the outer edge of the convection zone up to the stellar surface, and the equilibrium tide approximation is inconsistent with non–adiabaticity. Although this approximation generally applies in the low frequency limit, it also fails in the parts of the convection zone where the forcing frequency is small but larger than the Brunt-Väisälä frequency. We derive analytical estimates which give a good approximation to the numerical values of the magnitude of the ratio of the horizontal and radial displacements at the surface. The relative surface flux perturbation is also significant, on the order of 0.1% for a system modelled on 51 Pegasi b. Observations affected by the horizontal displacement may therefore be more achievable than previously thought, and brightness perturbations may be the result of flux perturbations rather than due to the radial displacement. We discuss the implication of this on the possibility of detecting such tidally excited oscillations, including the prospect of utilising the large horizontal motion for observations of systems such as 51 Pegasi.
VVV-WIT-04: an extragalactic variable source caught by the VVV Survey
Authors: Saito R K , Minniti D , Ivanov V D , Masetti N , Navarro M G , Cid Fernandes R , Ruschel-Dutra D , Smith L C , Lucas P W , Gonzalez-Fernandez C , Contreras Ramos R
Published: September 2019

We report the discovery of VVV-WIT-04, a near-infrared (near-IR) variable source towards the Galactic disc located ∼0.2 arcsec apart from the position of the radio source PMN J1515−5559. The object was found serendipitously in the near-IR data of the ESO public survey VISTA Variables in the Vía Láctea (VVV). Our analysis is based on variability, multicolour, and proper motion data from VVV and VVV eXtended surveys, complemented with archive data at longer wavelengths. We suggest that VVV-WIT-04 has an extragalactic origin as the near-IR counterpart of PMN J1515−5559. The Ks-band light curve of VVV-WIT-04 is highly variable and consistent with that of an optically violent variable quasar. The variability in the near-IR can be interpreted as the redshifted optical variability. Residuals to the proper motion vary with the magnitude suggesting contamination by a blended source. Alternative scenarios, including a transient event such as a nova or supernova, or even a binary microlensing event, are not in agreement with the available data.
RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells
Authors: Wang Yuru , Chung Dong hee , Monteleone Leanna R , Li Jie , Chiang Yao , Toney Michael D , Beal Peter A
Published: September 2019

Human ADAR3 is a catalytically inactive member of the Adenosine Deaminase Acting on RNA (ADAR) protein family, whose active members catalyze A-to-I RNA editing in metazoans. Until now, the reasons for the catalytic incapability of ADAR3 has not been defined and its biological function rarely explored. Yet, its exclusive expression in the brain and involvement in learning and memory suggest a central role in the nervous system. Here we describe the engineering of a catalytically active ADAR3 enzyme using a combination of computational design and functional screening. Five mutations (A389V, V485I, E527Q, Q549R and Q733D) engender RNA deaminase in human ADAR3. By way of its catalytic activity, the ADAR3 pentamutant was used to identify potential binding targets for wild type ADAR3 in a human glioblastoma cell line. Novel ADAR3 binding sites discovered in this manner include the 3′-UTRs of the mRNAs encoding early growth response 1 (EGR1) and dual specificity phosphatase 1 (DUSP1); both known to be activity-dependent immediate early genes that respond to stimuli in the brain. Further studies reveal that the wild type ADAR3 protein can regulate transcript levels for DUSP1 and EGR1, suggesting a novel role ADAR3 may play in brain function.
Can We Justify It? Trends in the Utilization of Spinal Fusions and Associated Reimbursement
Authors: Sheikh Shehryar Rahim , Thompson Nicolas R , Benzel Edward , Steinmetz Michael , Mroz Thomas , Tomic Dennis , Machado Andre , Jehi Lara
Published: September 2019

BACKGROUND

Previous reports have suggested an increasing rate of utilization of spinal fusions, but contemporary data have not been analyzed, and there has been little investigation of putative drivers of increased utilization.

OBJECTIVE

To investigate whether there is an ongoing trend of increased utilization of spinal fusions in recent data, and if there may be associations with an increasing proportion of elderly in the population, changing patterns of payer-types, and changing reimbursement rates.

METHODS

We analyze 7.1 million cases from the National Inpatient Sample between 1998 and 2014. We measure annual utilization per 100 000 persons and conduct trend analyses with subgroup analysis of the senior (65 + ) population. Spine surgery utilization is compared with nonspine surgical procedures (coronary artery bypass grafting, hernia repair, hip, and knee replacement). We assess trends in charges, payer type, Medicare reimbursement rates, and hospital type.

RESULTS

There was an 88% increase in the utilization rate of spinal fusion procedures from 1998 to 2014 (from 74 to 139 cases per 100 000 persons) with a significant upward trend (P < .001) that persisted in the 65 + subgroup (P < .001). An increasing proportion of spinal fusions is paid for by public payers, but per-procedure reimbursement for spinal fusions by Medicare has decreased recently (5% reduction from 2014 to 2016).

CONCLUSION

Utilization of spinal fusions continues to increase and is not explained by increased proportion of elderly in the population, increased utilization of surgeries across specialties, or increased Medicare reimbursement. In fact, increased utilization of spinal fusions temporally correlated with decreasing per-procedure Medicare reimbursement.
Introduction
Authors: Donahue-Ochoa Thomas J.
Published: September 2019

Among the world’s liberal elites today, a received view answers all five of the questions put by this book, arguing that systematic injustice is, essentially, persecution by a government; that there are no global social injustices; that individuals have a strong reason to challenge injustices only if they perpetrated or were victimized by them; that the individuals made unfree by systematic injustice are only its direct victims; and that the ultimate harm done by oppression is the unjust denial, to the oppressed, of the ability to live as free and equal citizens. Against this, the book’s introduction presents the theory of “Unfreedom for All,” which argues that oppressions are also institutional structures that privilege one group and unjustly harm another; that global systematic injustices of, say, race, gender, and poverty do exist; that all are harmed by oppressions because all are made unfree by them; and that this should be everyone’s main reason for joining in solidarity against them.
How Injustices Harm You
Authors: Donahue-Ochoa Thomas J.
Published: September 2019

Chapter 5 mounts the main argument of the book to show that oppression makes everyone unfree. The main ideas are that oppressions are despotic over their victims, that they can endure only if they try to suppress all actual or potential resistance, that any institutional feature of society that suppresses resistance has established authority, that institutional features with established authority are central social institutions, while suppressing resistance to central social institutions counts as authoritarian tactics used against everyone, that such tactics count as arbitrary power, and that to be subjected to such power is to be subjected to unfreedom of the kind theorized by neo-republicans and Hayekian competitive-order theorists. And since we all have a decent-life interest in freedom from arbitrary power, we are all harmed by such oppression, since it sets back this interest for everyone in society.
The Global Racial Order
Authors: Donahue-Ochoa Thomas J.
Published: September 2019

Chapter 7 offers a differential diagnosis of global racial injustice. Against Charles W. Mills’s theory that we live under global white supremacy, the chapter argues that the white racial group no longer dominates all other racial groups in the world. In particular, those raced as yellow by global society—roughly, East Asians and their descendants—are no longer dominated by racial whites and whiteness. More than this, the supreme political and social status enjoyed by whites over all other racial groups is also waning. The chapter therefore argues that our global racial order is best understood as a system of “partitioned white primacy.” In this system, racial whites exert racial primacy over racial reds, browns, and blacks; but the system is partitioned, because whites do not exert such primacy over those raced as yellow. Moreover, such primacy as whites do exert over other racial groups is less than supremacy, and it is even now being challenged. The chapter then shows how such primacy still suppresses resistance and thereby makes all unfree.
Solidarity, Universal Unfreedom, and You
Authors: Donahue-Ochoa Thomas J.
Published: September 2019

What should be our main reason for resisting oppression? In answer, chapter 9 argues that the universal unfreedom caused by oppression should be that reason, because we should seek a reason that will maximally appeal to the oppression’s non-victims, inducing them to resist and challenge it. For robust solidarity among a critical mass of the victims, the bystanders, and the perpetrators is necessary for abolishing systematic injustice and thus also for ending universal unfreedom. And because of the suspicion and mistrust that are likely to obtain in such a mixed resistance, we need a reason for challenging injustice that describes a shared harm the injustice does them all. The reason is that only a sense of such a shared harm could underwrite the robust and mutual solidarity needed to abolish oppression. Hence those non-victims who join in such solidarity are not allies but rather fellows who are also harmed: they are the scathed.
Mass Supervision
Authors: Andreas Joel
Published: September 2019

Chapter 4 examines the Four Cleans movement (1962–1966), the largest and most protracted campaign carried out to that point to mobilize “supervision from below” of party cadres. Supervision from below had been hindered by the Communist Party’s inclination to tightly control all aspects of participation as it was impossible for workers to effectively play their role if they did not have a degree of autonomy from the factory cadres they were expected to supervise. Mao attempted to mitigate this problem by sending in teams of outside party cadres to organize workers to criticize factory party leaders. The Four Cleans campaign was effective in combatting corruption but less effective in dealing with Mao’s main concern—the transformation of the party officialdom into a privileged “bureaucratic class” unaccountable to their subordinates. Dissatisfaction with the results led Mao to launch a much more radical attempt to introduce autonomy into mass supervision.