bluuebunny/crossref_metadata_2025 huggingface dataset:
PCM Integrated in BiPV Ventilated Façade Concepts: Experimental Test Cell Platform and Initial Full-Scale Measurements
Authors: Curpek J , Cekon M , Hraska J
Published: June 2019

Recently, a wide range of novel façade solutions directly utilizing solar energy has been described as Building Integrated Photovoltaic (BiPV). However, there are still barriers (e.g. cells’ overheating) to overcome in order to promote widespread application of BiPV concepts. Therefore PV/PCM systems have been already studied to improve the performance of PV, however their integration in building (BiPV/PCM) is still not adequately investigated. In this regard, the main objective of this paper is to present one of the viable way of investigation a novel combination of BiPV/PCM. This can utilize PV cells cooling principle at behind of the BiPV layer in ventilated façade. The key research methods are based on the experimental and building energy simulation studies. For this purpose, a specific experimental test platform was developed to provide experimental measurements on ongoing long-term full-scale level in Brno, Czechia. Two types of ventilated BiPV façade are tested there with/without PCM layer behind the PV cells. The paper introduces the test platform which is used for evaluation of specific aspects of integrated PCMs in BiPV management and demonstrates the initial thermal response measurements. The influence of PCMs on the real performance of the BiPV façade and effectivity of application of latent thermal energy storage used on reduction of the peak operating temperatures of the PV modules as well as shifting of air temperature inside the façade cavity is analysed. Finally, the extensive measurements provide real performance data that will be used to verify the building energy simulations.
Potential Benefits of PV-Shading System in Office Buildings and Semi-Continental Climate Conditions
Authors: Skandalos N , Tywoniak J , Stanek K
Published: June 2019

Solar PV shading devices are good solutions to control daylight and reduce the unwanted solar gains, while generate electricity at the same time. Since thermal, electrical and daylighting performance competing each other, it is imperative to consider specific design criteria to optimize and allow energy efficient level of thermal and visual performance. In this context, the study focus on the optimum design of PV shading devices for typical office building with high fenestration ratio and climate conditions of Prague. TRNsys simulation environment was used for the evaluation of the power and thermal performance of the PV shadings considering various tilt angles, projection depth and orientations. Ecotect/Daysim software tools were used to evaluate the daylighting performance and lighting energy use. Useful Daylight Illuminance (UDI) and Discomfort Glare Probability (DGP) indices were also calculated for indoor visual comfort analysis according to the design configuration. Results were overall evaluated to reveal the potential energy benefits compared to the non-shaded case. The study serves as a guide for the optimum design of PV shading systems.
Determination of Moisture Buffering Capabilities of Common Furniture Materials
Authors: Zemitis J , Borodinecs A
Published: June 2019

According to previous existing studies, the building materials can have a high impact on relative humidity fluctuations in a room by adsorption/desorption processes. The aim of this paper is focused to determine the influence of commonly used furniture materials to indoor air relative humidity. The measurements were performed in a controlled environment of the climatic chamber. During the measurements, a stable indoor temperature together with a constant air moistening was ensured. The indoor air parameters were measured with data loggers as well as the periodical weighting of materials was performed, to determine the moisture content of materials. The results showed that the common furniture materials have a very significant impact on indoor air relative humidity. The calculations of the influence were performed according to the mass balance equation comparing the predicted results without considering the influence of materials to the actual measured results from real case studies, therefore estimating the adsorption capabilities of these materials. The influence of these materials to the stabilization of indoor relative humidity can be expressed as a coefficient in mass balance equation depending on the type of material, area, and thickness of material, initial moisture content, and indoor air parameters. The findings of these results can be used in the design stage of indoor climatic systems to more precisely predict the relative humidity.
Solar Aperture of a Building Enclosure: The Case Study of a Well-Insulated Family House in Semi-Continental Climate
Authors: Kopecký P , Sojková K
Published: June 2019

As thermal insulation of building enclosure has substantially improved over the last decades, solar heat gains comprise more important part in thermal balance of a building in semi-continental climate, often leading to overheating. The quality of the whole building enclosure should be assessed by its ability to transmit solar heat gains. Such thermal characteristic need to aggregate properties like glazing area in each facade, total solar energy transmittance of glazing, the efficiency of fixed shading devices and the operation of movable shading devices. In this paper, the surrogate horizontal effective collector area is used for the characterization of solar heat gains through a building enclosure. The parameter is called the solar aperture of a building enclosure. First, the formula for solar aperture is derived. Then, building energy simulation of a model family house is performed. The correlation of the solar aperture with overheating and space heating demand is analysed. Based on the analysis, the recommended trade-off values of the specific solar aperture are proposed for family houses in semi-continental climate. The trade-off values of the solar aperture will lead to reasonable promotion of solar heat gains during cold season and significant reduction of solar heat gains during warm season.
The Impacts of the Exterior Glazed Structures and Orientation on the Energy Consumption of the Building
Authors: Odineca T , Borodinecs A , Korjakins A , Zajecs D
Published: June 2019

Buildings use about 40% of the national energy consumption, and approximately 25-30% of this energy is wasted due to inefficient windows. Installation of energy efficient glazing allows significant reduction of cooling load. While increase of hat consumption can be observed in heating period due to significant reduction of solar heat gains. On the basis of computer simulations there were found dependences between overall energy efficiency of the building and such parameters as its orientation, urbanization, and the types of glazing. Building energy modelling (BEM) allows to predict the energy consumption of the building, to find and correct the weak spots in terms of energy consumption and to find the most effective way to use energy saving technologies. The IDA-ICE, chosen as the BEM in the research, is a whole-year detailed and dynamic multi-zone simulation application for study of thermal indoor climate and the entire building energy consumption. The main advantage of the software package is a detailed report for each of the building zones and for the whole building, which includes calculation of heat flows and inflows, maintained temperatures, sources of heat losses and energy costs to maintain a comfort temperature. The variable data are the type of glazing (different window types chosen, with special emphasis on g-value of glass and coefficient of shading) and building’s orientation to the world sides. The research demonstrates the effectiveness of using particular glazing types depending on the building conditions. The developed recommendations allow to reduce energy consumption in existing buildings and to reduce construction costs of new office buildings at the design stage.
The Influence of Heat Gains on the Heating System Design
Authors: Spurny J , Kabrhel M
Published: June 2019

The article deals with the influence of heat loss of the distribution piping system and the related cooling of the heating water on the design of two-pipe counter-current heating system. The heat loss of the heating water distribution system to the heated room were observed on a reference family house. Consideration of heat gains is particularly important for low energy houses. Moreover, the consequences of heat gains to the room and its effect to the required radiator power output design were solved for case when the piping distribution system is placed visible on the wall and without thermal insulation. The effect is also evident with thermal insulation or embedded pipelines. Furthermore, mass flows and temperature gradients at the same mean temperature were observed on all radiators. This calculation was compared to the results of classic calculation design.
A Feasibility Study on the Waste-to-Biogas SOFC-Based Multi-Generation with Energy Storage System for Building Applications in China
Authors: Zhang S , Wang Q , Hu L , Shi W , Qu M
Published: June 2019

The Waste-to-Energy Multi-generation system provides a feasible distributed waste recycling and energy saving solution for green buildings. However, the fluctuations in electricity demands and dynamic built environment obstruct its marketization. This study optimizes the existing waste-biogas-SOFC multi-generation configuration with energy storage systems. The research employs the operation data from an international airport in Southern China as a case study. The study compares the proposed system and that of previous SOFC-based systems in terms of economic and environmental benefits. The results show that the demand and supply of energy is balanced and higher energy efficiency and a significant reduction in the Greenhouse Gas (GHG) emission is achieved. The system presents a solid performance in payback and lifecycle cost (LCC) analysis and also satisfactory resistance to financial risks. Finally, this study draws the conclusion that the energy storage system could be utilized to optimize the existing SOFC multi-generation system.
System Model for Prediction of Energy Consumption in Cities
Authors: Vytlačil D
Published: June 2019

The number of inhabitants in cities has been increasing in the past years and this tendency will be in the future even more significant. We need a tool for the prediction of the energy consumption. The paper describes the system model that includes sub models: the energy consumed for housing, inhabitants services, city services and transport. These sub models are interconnected to one system. The solution is based on the system dynamics methodology which is suitable tool for solving problems of economic and technical systems. Special focus is given on the description of the energy consumptions in the residential houses, in the buildings providing city service and on the migration of people from rural area and small cities to big cities. The number of inhabitants influences the energy consumption and the density that is connected to the energy consumption for the transport. The simulation includes the refurbishment of the existing building stock. Main output parameter is the energy consumption in the sub models and in the whole city. The model can help to improve the strategy decision making concerning city development.
A Bibliometric Analysis on Costs Estimation of Building Retrofit
Authors: Re Cecconi F , Moretti N , Dejaco M C
Published: June 2019

Buildings are responsible for approximatively 40% of energy consumptions and 36% of CO2 emissions in the EU. In developed countries, any intervention carried out for buildings’ sustainability improvement is related to energy retrofit. Energy retrofit can be considered as a subset of sustainability management and is one of the key issues to be taken into account for the setup of an effective asset and portfolio management strategy. Among asset management core functions, sustainability management is one of those which must be encompassed in a strategic framework for effectively reaching the goals of the organisation. Within this context, sustainability of buildings should be evaluated according to the environmental, economic and social point of view. These different issues require specific assessment methodologies and metrics. Therefore, in this article, a bibliometric analysis on costs estimation is presented, focusing on Life Cycle Costing methodology for energy retrofit interventions. Articles have been investigated through bibliometric, trend and cluster analysis on a sample of 167 articles. The research has been carried out on one of the most acknowledged databases as Scopus and allowed to identify main trends and dynamics of the scientific literature.
Historical Water Management Constructions, their Value, Function and Significance
Authors: Nedvedova K , Dzurakova M , Vyskocil A , Svitak Z , Kleparnikova R , Honek D
Published: June 2019

The contribution would like to present a new research project focused on expansion of the knowledge, systematic documentation and definition of objective criteria for the evaluation of a specific group of technical monuments – historical water management constructions. The main goal is to develop a methodology of unambiguous identification, categorization and evaluation of historical water management objects in terms of historic preservation and renewal, based on an interdisciplinary approach.

Attainment of the project’s goals through:

- documentation and analysis of the water management objects’ evolution in chosen study areas, using historical topographical maps of five different periods, as well as archive sources,

- comparative analysis of the historical water management objects’ development in study areas, taking into consideration different conditions both natural and socio-economic

The project’s outcomes will be:

- a set of maps,

- the methodology of identification, categorization and evaluation of historical water management objects. The methodology will be a significant contribution to further research activities involving documentation, evaluation, preservation and renewal of this specific cultural heritage fund.
Greening Actions and the Related Potential Impacts on Outdoor Comfort in a Dense Built Environment
Authors: Gaspari J , Fabbri K
Published: June 2019

The increasing attention paid to the effects of climate change on the dense urban fabric of contemporary cities had led Public Authorities to develop local adaptation plans in order to suggest some effective measures to mitigate and reduce the impacts of urban heat island [UHI] and heat waves as well as to improve water management capacity. Among the suggested actions, the greening of in-between spaces of the built environment and the introduction of new green surfaces (roof and/or facades) in the framework of wider regeneration plans offers interesting perspectives and impacts. The paper reports the outcomes of a research activity run by the Department of Architecture and the Municipality of Bologna to investigate how to define/optimize the most effective arrangement of greening solutions with the aim to improve outdoor comfort conditions. The study takes into account several aspects including paved/green surfaces extension, the use of material, the geometry of the site, etc. and simulate the potential effects of changes using simulation software ENVIMET. Once the main features of each site are modelled the different deriving scenarios can be compared evaluating the different architectural, economical and practical constraints. The results are then compared with other factors, related to the social aspects, the use of the spaces, the perception of the sites, etc. A district of the city of Bologna is used as test bed in order to test the proposed methodology and the related potential impacts.
Functional Aging Index Complements Frailty in Prediction of Entry Into Care and Mortality
Authors: Finkel Deborah , Sternäng Ola , Jylhävä Juulia , Bai Ge , Pedersen Nancy L
Published: June 2019

Background

The aim of this study was to develop a functional aging index (FAI) that taps four body systems: sensory (vision and hearing), pulmonary, strength (grip strength), and movement (gait speed) and to test the predictive value of FAI for entry into care and mortality.

Method

Growth curve models and Cox regression models were applied to data from 1,695 individuals from three Swedish longitudinal studies of aging. Participants were aged 45–93 at intake and data from up to eight follow-up waves were available.

Results

The rate of change in FAI was twice as fast after age 75 as before, women demonstrated higher mean FAI, but no sex differences in rates of change with chronological age were identified. FAI predicted entry into care and mortality, even when chronological age and a frailty index were included in the models. Hazard ratios indicated that FAI was a more important predictor of entry into care for men than women, whereas it was a stronger predictor of mortality for men than women.

Conclusions

Measures of biological aging and functional aging differ in their predictive value for entry into care and mortality for men and women, suggesting that both are necessary for a complete picture of the aging process across genders.
Neuregulin-4 Is Required for the Growth and Elaboration of Striatal Medium Spiny Neuron Dendrites
Authors: Paramo Blanca , Wyatt Sean , Davies Alun M
Published: June 2019

Medium spiny neurons (MSNs) comprise the vast majority of neurons in the striatum. Changes in the exuberant dendrites of these widely connected neurons are associated with a multitude of neurological conditions and are caused by a variety of recreational and medicinal drugs. However, we have a poor understanding of the physiological regulators of dendrite growth and elaboration of this clinically important population of neurons. Here, we show that MSN dendrites are markedly smaller and less branched in neonatal mice that possess a homozygous null mutation in the neuregulin-4 gene (Nrg4−/−) compared with wild type (Nrg4+/+) littermates. Nrg4−/− mice also had a highly significant reduction in MSN dendrite spine number in neonates and adults. The striking stunted dendrite arbor phenotype of MSNs observed in Nrg4−/− neonates was replicated in MSNs cultured from Nrg4−/− embryos and was completely rescued by soluble recombinant neuregulin-4. MSNs cultured from wild type mice coexpressed NRG4 and its receptor ErbB4. Our findings show that NRG4 is a major novel regulator of dendritic growth and arborization and spine formation in the striatum and suggest that it exerts its effects by an autocrine/paracrine mechanism.
Music Therapy Degree Program Enrollment Trends: What the Numbers Tell Us
Authors: Iwamasa Dawn A
Published: June 2019

Music therapy educational programs have expanded since their inception in the 1940s, but no studies have examined the trends regarding enrollment and degree attainment in music therapy. The purpose of this study was to investigate the trends in music therapy undergraduate and graduate program enrollment and degree attainment from 2000 to 2017. Data were collected from the Council of Arts Accrediting Associations’ Higher Education Arts Data Services (HEADS) survey for music therapy and all other music majors’ combined program enrollment and degree attainment. Additionally, data from the National Center for Education Statistics (NCES) were used to compare music therapy and all other combined music major trends with those from all 4-year degree-granting postsecondary institutions. Results indicated that music therapy program enrollment and degree attainment at the undergraduate and graduate levels are growing at a faster pace than all other music majors combined—and at all 4-year degree-granting postsecondary institutions. Economic theories that may explain this phenomenon are discussed, as are implications for future research.
Bow Hunter's Syndrome: Complete Microsurgical Decompression of Vertebral Artery by Far Lateral Retrocondylar Approach: 3-Dimensional Operative Video
Authors: Zeeshan Qazi , Hernandez Juan P Carrasco , Sekhar Laligam N
Published: June 2019

This 50-yr-old man had a 15-yr history of presyncopal episodes that were precipitated by turning his head to the right, and had worsened recently. Cerebral angiogram demonstrated complete cessation of anterograde flow in left vertebral artery (VA) at the level of the C1 sulcus arteriosus while turning head to right, indicating dynamic compression at the C1 level.

 Patient underwent left extreme lateral retrocondylar approach, partial C1 laminectomy and opening of the C1 foramen with complete microsurgical decompression of the VA. After skin incision, meticulous muscle dissection was performed and superior and inferior oblique muscles were disconnected from the tubercle of C1. The VA was exposed, and three areas of constriction were visible, first at the atlanto-occipital membrane laterally; second, located more medially as the artery curved around the occipital condyle to enter the posterior fossa; and third, located anterior to C2 nerve root. The artery was dissected from all the surrounding tissues, preserving the C2 nerve root, and the Cl foramen was opened completely. The Cl lamina was also partially resected and grooved to allow free placement of the VA. The VA was also decompressed near the C2 foramen. Postoperative computed tomography angiogram of the head and neck showed complete decompression of VA. The patient had no episodes of presyncope or dizziness while turning head to right and his mRs was 0 at 8 mo follow up.

 This 3D video shows the technical nuances of decompression of V3 segment of VA in bow hunters's syndrome.

 Informed consent was obtained from the patient prior to the surgery that included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides.
Techniques to Improve the Efficacy of Percutaneous Biopsy Procedures for Cavernous Sinus Lesions
Authors: Scranton Robert A , Cohen-Gadol Aaron A
Published: June 2019

BACKGROUND

The cavernous sinus can be affected by pathologies with profound clinical implications. Therefore, obtaining an accurate diagnosis with minimal disruption of native tissue is needed. Percutaneous needle aspiration biopsy through the foramen ovale using the Härtel corridor is one option. The diagnostic yield is around 86%, typically failing in cases where the tissue is firm.

OBJECTIVE

This work describes a new method of percutaneous biopsy to increase the diagnostic yield in cases where the tissue is firm and not deliverable into the biopsy needle via a suction device.

METHODS

Under general anesthetic, a percutaneous approach through the foramen ovale was performed. A k-wire was then placed and the needle was removed. A 14-ga angiocatheter was then placed using the over-the-wire technique. Once the K-wire was removed, endoscopic graspers were used to biopsy the lesion through the angiocatheter, providing reasonably sized biopsy specimens.

RESULTS

This technique was applied when fine needle aspiration failed and resulted in successful pathologic diagnosis.

CONCLUSION

This technique for minimally invasive biopsy of the cavernous sinus is potentially safe and can be performed when fine needle aspiration is unsuccessful or larger samples are required for definitive diagnosis.
Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian randomization study based on 79,148 prostate cancer cases and 61,106 controls
Authors: Kazmi Nabila , Haycock Philip , Tsilidis Konstantinos , Lynch Brigid M. , Truong Therese ,   the PRACTICAL consortium,   CRUK,   BPC3,   CAPS,   PEGASUS, Martin Richard M , Lewis Sarah
Published: June 2019

Background

Prostate cancer is the second most common male cancer worldwide, but there is substantial geographical variation suggesting a potential role for modifiable risk factors in prostate carcinogenesis.

Methods

We identified previously reported prostate cancer risk factors from the World Cancer Research Fund’s (WCRF) systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79,148 cases and 61,106 controls) or aggressive (15,167 cases and 58,308 controls) prostate cancer using Mendelian randomization (MR) based on genome wide association study (GWAS) summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7,844 prostate cancer cases and 204,001 controls).

Findings

WCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms (SNPs). In MR analyses for overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical-activity, OR=0.49 (0.33-0.72; p=0.0003); serum iron, OR=0.92 (0.86-0.98; p=0.007); body mass index (BMI), OR=0.90 (0.84-0.97; p=0.003); and mono-unsaturated fat, OR=1.11 (1.02-1.20; p=0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive prostate cancer risk: OR=1.07 (1.01-1.15; p=0.03).

Interpretation

The results for physical-activity, serum iron, BMI, mono-unsaturated fat and height are compatible with causality for prostate cancer but more research is needed to rule out violations of MR assumptions for some risk factors. The results suggest that interventions aimed at increasing physical activity may reduce prostate cancer risk, but the direction of effects of BMI, and iron are at odds with their effects on other diseases, so the overall public health impact of intervening on these need to be considered.

Funding

World Cancer Research Fund International (2015/1421), Cancer Research UK program grant (C18281/A19169), National Institute for Health Research, Bristol Biomedical Research Centre, and Victorian Cancer Agency (MCRF18005).
How to maintain a high virulence: evolution of a killer in hosts of various susceptibilities
Authors: Chateigner Aurélien , Moreau Yannis , Jiolle Davy , Pontlevé Cindy , Labrousse Carole , Bézier Annie , Herniou Elisabeth
Published: June 2019

Pathogens should evolve to avirulence. However, while baculoviruses can be transmitted through direct contact, their main route of infection goes through the death and liquefaction of their caterpillar hosts and highly virulent strains still seem to be advantaged through infection cycles. Furthermore, one of them,Autographa californicamultiple nucleopolyhedrovirus, is so generalist that it can infect more than 100 different hosts.

To understand and characterize the evolutionary potential of this virus and how it is maintained while killing some of its hosts in less than a week, we performed an experimental evolution starting from an almost natural isolate of AcMNPV, known for its generalist infection capacity. We made it evolve on 4 hosts of different susceptibilities for 10 cycles and followed hosts survival each day. We finally evaluated whether the generalist capacity was maintained after evolving on one specific host species and tested an epidemiological model through simulations to understand how.

Finally, on very highly susceptible hosts, transmission-virulence trade-offs seem to disappear and the virus can maximize transmission and virulence. When less adapted to its host, the pathogen’s virulence has not been modified along cycles but the yield was increased, apparently through an increased transmission probability and an increased latent period between exposition and infection.
Injectable diblock copolypeptide hydrogel provides platform to maintain high local concentrations of taxol and local tumor control
Authors: Garrett Matthew C. , O’Shea Timothy M. , Wollenberg Alexander L. , Bernstein Alexander M. , Hung Derek , Staarman Brittany , Soto Horacio , Deming Timothy J. , Sofroniew Michael V. , Kornblum Harley I.
Published: June 2019

Introduction

Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.

Methods

The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.

Results

The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model, of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to a high local concentration of paclitaxel and led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.

Conclusions

These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.
Effect of Alpha-Lactalbumin and Lactoferrin Oleic Acid Complexes on Chromatin Structural Organization
Authors: Lebedev Dmitry V , Zabrodskaya Yana A , Pipich Vitaly , Kuklin Alexander I , Ramsay Edward , Sokolov Alexey V , Elizarova Anna Yu , Shaldzhyan Aram A , Grudinina Natalia A , Pantina Rimma A , Wu Baohu , Shtam Tatiana A , Volnitskiy Andrey V , Shmidt Alexander E , Shvetsov Alexey V , Isaev-Ivanov Vladimir V , Egorov Vladimir V
Published: June 2019

This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alpha-lactalbumin (hAl) or with bovine alpha-lactalbumin (bAl), and human lactoferrin (hLf) were investigated using small-angle neutron scattering (SANS). It was shown that while alpha-lactalbumin protein complexes were formed on the surface of polydisperse OA micelles, the lactoferrin complexes comprised a monodisperse system of nanoscale particles. Both hAl and hLf complexes appeared to interact with the chromatin of isolated nuclei affecting chromatin structural organization. The possible roles of these processes in the specific anti-tumor activity of these complexes are discussed.
Floral signals evolve in a predictable way under artificial and pollinator selection inBrassica rapausing a G-matrix
Authors: Zu Pengjuan , Schiestl Florian P. , Gervasi Daniel , Li Xin , Runcie Daniel , Guillaume Frédéric
Published: June 2019

Background

Angiosperms employ an astonishing variety of visual and olfactory floral signals that are generally thought to evolve under natural selection. Those morphological and chemical traits can form highly correlated sets of traits. It is not always clear which of these are used by pollinators as primary targets of selection and which would be indirectly selected by being linked to those primary targets. Quantitative genetics tools for predicting multiple traits response to selection have been developed since long and have advanced our understanding of evolution of genetically correlated traits in various biological systems. We use these tools to predict the evolutionary trajectories of floral traits and understand the selection pressures acting on them.

Results

We used data from an artificial and a pollinator (bumblebee, hoverfly) selection experiment with fast cyclingBrassica rapaplants to predict evolutionary changes of 12 floral volatiles and 4 morphological floral traits in response to selection. Using the observed selection gradients and the genetic variance-covariance matrix (G-matrix) of the traits, we showed that the responses of most floral traits including volatiles were predicted in the right direction in artificial- and bumblebee-selection experiment, revealing direct and indirect targets of bumblebee selection. Genetic covariance had a mix of constraining and facilitating effects on evolutionary responses. We further revealed how G-matrices evolved in the selection processes.

Conclusions

Overall, our integrative study shows that floral signals, and especially volatiles, evolve under selection in a mostly predictable way, at least during short term evolution. Evolutionary constraints stemming from genetic covariance affected traits evolutionary trajectories and thus it is important to include genetic covariance for predicting the evolutionary changes of a comprehensive suite of traits. Other processes such as resource limitation and selfing also needs to be considered for a better understanding of floral trait evolution.
Phosphoprotein-based Biomarkers as Predictors for Cancer Therapy
Authors: Carter Angela M. , Tan Chunfeng , Pozo Karine , Telange Rahul , Molinaro Roberto , Guo Ailan , De Rosa Enrica , Martinez Jonathan O. , Zhang Shanrong , Kumar Nilesh , Takahashi Masaya , Wiederhold Thorsten , Ghayee Hans K. , Oltmann Sarah C. , Pacak Karel , Woltering Eugene A. , Hatanpaa Kimmo J. , Nwariaku Fiemu E. , Grubbs Elizabeth G. , Gill Anthony J , Robinson Bruce , Gillardon Frank , Reddy Sushanth , Jaskula-Sztul Renata , Mobley James A. , Mukhtar M. Shahid , Tasciotti Ennio , Chen Herbert , Bibb James A.
Published: June 2019

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. non-sensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of human patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified novel phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers of Cdk5 activity and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.
BOLD Decoding of Individual Pain Anticipation Biases During Uncertainty
Authors: Kadlec Molly , Tosun Duygu , Strigo Irina
Published: June 2019

A prominent model of pain as a predictive cue posits that anticipation shapes pain transmission and ultimately pain experience. Consistent with this model, the neural mechanisms underlying pain anticipation have the power to modulate pain experience thus understanding pain predictions, particularly during uncertainty, may allow us to ascertain measures indicative of intrinsic anticipation biases. Understanding such biases moves way to precision pain management, as it can guide the individualized treatment. To examine individual pain anticipation biases, we applied machine-learning-based neural decoding to functional magnetic resonance imaging (fMRI) data acquired during a pain-anticipation paradigm to identify individualized neural activation patterns differentiating two certain anticipatory conditions, which we then used to decode that individual’s uncertain anticipatory condition. We showed that neural patterns representative of the individualized response during certain anticipatory conditions were differentiable with high accuracy and, across individuals, most commonly involved neural activation patterns within anterior short gyrus of the insula and the nucleus accumbens. Using unsupervised clustering of individualized decodings of anticipatory responses during uncertain conditions, we identified three distinct response profiles representing subjects who, in uncertain situations, consistently anticipated high-pain (i.e., negative bias), subjects who consistently anticipated low-pain (i.e., positive bias), and subjects whose decoded anticipation responses were depended on the intensity of the preceding pain stimulus. The individualized decoded pain anticipation biases during uncertainty were independent of existence or type of diagnosed psychopathology, were stable over one year timespan and were related to underlying insula anatomy. Our results suggest that anticipation behaviors may be intrinsic, stable, and specific to each individual. Understanding individual differences in the neurobiology of pain anticipation has the potential to greatly improve the clinical pain management.
Genome-wide and enzymatic analysis reveals efficient D-galacturonic acid metabolism in the basidiomycete yeastRhodosporidium toruloides
Authors: Protzko Ryan J. , Hach Christina A. , Coradetti Samuel T. , Hackhofer Magdalena A. , Magosch Sonja , Thieme Nils , Arkin Adam P. , Skerker Jeffrey M. , Dueber John E. , Benz J. Philipp
Published: June 2019

Biorefining of renewable feedstocks is one of the most promising routes to replace fossil-based products. Since many common fermentation hosts, such asSaccharomyces cerevisiae, are naturally unable to convert many component plant cell wall polysaccharides, the identification of organisms with broad catabolism capabilities represents an opportunity to expand the range of substrates used in fermentation biorefinery approaches. The red basidiomycete yeastRhodosporidium toruloidesis a promising and robust host for lipid and terpene derived chemicals. Previous studies demonstrated assimilation of a range of substrates, from C5/C6-sugars to aromatic molecules similar to lignin monomers. In the current study, we analyzedR. toruloidespotential to assimilate D-galacturonic acid, a major sugar in many pectin-rich agricultural waste streams, including sugar beet pulp and citrus peels. D-galacturonic acid is not a preferred substrate for many fungi, but its metabolism was found to be on par with D-glucose and D-xylose inR. toruloides. A genome-wide analysis by combined RNAseq/RB-TDNAseq revealed those genes with high relevance for fitness on D-galacturonic acid. WhileR. toruloideswas found to utilize the same non-phosphorylative catabolic pathway known from ascomycetes, the maximal velocities of several enzymes exceeded those previously reported. In addition, an efficient downstream glycerol catabolism and a novel transcription factor were found to be important for D-galacturonic acid utilization. These results set the basis for use ofR. toruloidesas a potential host for pectin-rich waste conversions and demonstrate its suitability as a model for metabolic studies in basidiomycetes.

Importance

The switch from the traditional fossil-based industry to a green and sustainable bio-economy demands the complete utilization of renewable feedstocks. Many currently used bio-conversion hosts are unable to utilize major components of plant biomass, warranting the identification of microorganisms with broader catabolic capacity and characterization of their unique biochemical pathways. D-galacturonic acid is a plant component of bio-conversion interest and is the major backbone sugar of pectin, a plant cell wall polysaccharide abundant in soft and young plant tissues. The red basidiomycete and oleaginous yeastRhodosporidium toruloideshas been previously shown to utilize a range of sugars and aromatic molecules. Using state-of-the-art functional genomic methods, physiological and biochemical assays, we elucidated the molecular basis underlying the efficient metabolism of D-galacturonic acid. This study identifies an efficient pathway for uronic acid conversion to guide future engineering efforts, and represents the first detailed metabolic analysis of pectin metabolism in a basidiomycete fungus.
Stalk Bending Strength is Strongly Associated with Maize Stalk Lodging Incidence Across Multiple Environments
Authors: Sekhon Rajandeep S. , Joyner Chase N. , Ackerman Arlyn J. , McMahan Christopher S. , Cook Douglas D. , Robertson Daniel J.
Published: June 2019

Stalk lodging in maize results in substantial yield losses worldwide. These losses could be prevented through genetic improvement. However, breeding efforts and genetics studies are hindered by lack of a robust and economical phenotyping method for assessing stalk lodging resistance. A field-based phenotyping platform that induces failure patterns consistent with natural stalk lodging events and measures stalk bending strength in field-grown plants was recently developed. Here we examine the association between data gathered from this new phenotyping platform with counts of stalk lodging incidence on a select group of maize hybrids. For comparative purposes, we examine four additional predictive phenotypes commonly assumed to be related to stalk lodging resistance; namely, rind puncture resistance, cellulose, hemicellulose, and lignin. Historical counts of lodging incidence were gathered on 47 hybrids, grown in 98 distinct environments, spanning four years and 41 unique geographical locations in North America. Using Bayesian generalized linear mixed effects models, we show that stalk lodging incidence is associated with each of the five predictive phenotypes. Further, based on a joint analysis we demonstrate that, among the phenotypes considered, stalk bending strength measured by the new phenotyping platform is the most important predictive phenotype of naturally occurring stalk lodging incidence in maize, followed by rind puncture resistance and cellulose content. This study demonstrates that field-based measurements of stalk bending strength provide a reliable estimate of stalk lodging incidence. The stalk bending strength data acquired from the new phenotyping platform will be valuable for phenotypic selection in breeding programs and for generating mechanistic insights into the genetic regulation of stalk lodging resistance.
Defining the microenvironment landscape of bladder cancer using highly multiplexed spatial genomic and proteomic analysis
Authors: Reeves Jason W , Zhang Zhaojie , Norgaard Zachary K , Zhou Denise M , Gong JingJing , Liang Yan , Das Subhasree , Warren Sarah E , Korpal Manav , Hoang Margaret L , Beechem Joseph M , Kumar Pavan , Rimkunas Victoria
Published: June 2019

Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. PD-1 pathway targeting immunotherapies have been approved to treat advanced bladder cancer, but most patients exhibit primary resistance, suggesting that immune evasion mechanisms exist. The PPARγ pathway has been identified as a potential therapeutic target in MIBC that is associated with reduced CD8+ T-cell infiltration and increased resistance to immunotherapies. We comprehensively profiled the tumor microenvironment (TME) in formalin-fixed, paraffin-embedded (FFPE) tissues from a cohort of PPARγhigh (n=13) and PPRARγlow (n=12) MIBC, integrating bulk gene expression, targeted mutation sequencing, immunohistochemistry and multiplex spatial profiling of RNA and protein expression on the GeoMx™ Digital Spatial Profiling (DSP) platform. Molecular subtyping was consistent between traditional methods and GeoMx profiling, and, in this cohort, we observed little evidence of spatial heterogeneity in tumor subtyping. The previously characterized T-cell exclusion phenotype of PPARγhigh MIBC was recapitulated on the GeoMx platform and was further extended to show that this is a general phenomenon across immune cell types, supporting potential combination of PPARγ inhibition with ICIs. Furthermore, we found that while immune cells were excluded from PPARγhigh tumors, the stromal compartment from these tumors was not significantly different than those PPARγlow tumors. By preserving spatial relationships during the GeoMx analysis, we also identify a novel association between lower immune cell expression in the tumors and higher expression of β-catenin in the stroma, and differential expression of other WNT pathway members associated with PPARγ activity.

One Sentence Summary

A new method for capturing tumor-immune signaling in FFPE tissues explores how the PPARG signaling axis is associated with immune cell exclusion in bladder cancer.
Visual mapping on the brain - caveats for multifocal fMRI
Authors: Crewther David P. , Seixas Shaun A. S. , Crewther Sheila G.
Published: June 2019

While multifocal electroretinography has become a standard ophthalmological technique, its use in cortical neuroimaging has been lesser. Vanni et al. (2005) presented the first exploration of the multifocal visual mapping methodology with fMRI. This commentary confirms the utility of this method, but also presents empirical results which suggest caveats for the use of the technique. In the current study rapid multifocal fMRI was established using m-sequence pseudo-random binary stimuli applied to visual field mapping in six young adults with normal vision. Nine contiguous regions of visual field – two rings of 4 patches with a central patch, areas scaled for cortical magnification, were pseudo-randomly stimulated, with patterned or grey images. The decorrelation of stimulus patches allowed all 256 volumes to be used for the analysis of each of the nine stimulus areas. Strong localized activation was observed for each of the four peripheral regions with the location of the activation conforming to the expected visual field retinotopy. The inner regions, including the foveal patch, did not significantly activate. We propose, on the basis of a simple correlational model of simulated eye movements, that the loss of signal is due to gaze instability. Thus, while the rapid multifocal method can be successfully applied to fMRI, the results appear quite sensitive to eye movements, the effects of which may have been overlooked by smoothing evoked responses to achieve a retinotopic map.