bluuebunny/crossref_metadata_2025_split huggingface dataset:
Petrov–Galerkin space-time hp-approximation of parabolic equations in H1/2
Authors: Devaud Denis 
Published: August 2019

Abstract
We analyse a class of variational space-time discretizations for a broad class of initial boundary value problems for linear, parabolic evolution equations. The space-time variational formulation is based on fractional Sobolev spaces of order $1/2$ and the Riemann–Liouville derivative of order $1/2$ with respect to the temporal variable. It accommodates general, conforming space discretizations and naturally accommodates discretization of infinite horizon evolution problems. We prove an inf-sup condition for $hp$-time semidiscretizations with an explicit expression of stable test functions given in terms of Hilbert transforms of the corresponding trial functions; inf-sup constants are independent of temporal order and the time-step sequences, allowing quasi-optimal, high-order discretizations on graded time-step sequences, and also $hp$-time discretizations. For solutions exhibiting Gevrey regularity in time and taking values in certain weighted Bochner spaces, we establish novel exponential convergence estimates in terms of $N_t$, the number of (elliptic) spatial problems to be solved. The space-time variational setting allows general space discretizations and, in particular, for spatial $hp$-FEM discretizations. We report numerical tests of the method for model problems in one space dimension with typical singular solutions in the spatial and temporal variable. $hp$-discretizations in both spatial and temporal variables are used without any loss of stability, resulting in overall exponential convergence of the space-time discretization.
Sulphur systems biology—making sense of omics data
Authors: Watanabe Mutsumi , Hoefgen Rainer 
Published: August 2019

AbstractSystems biology approaches have been applied over the last two decades to study plant sulphur metabolism. These ‘sulphur-omics’ approaches have been developed in parallel with the advancing field of systems biology, which is characterized by permanent improvements of high-throughput methods to obtain system-wide data. The aim is to obtain a holistic view of sulphur metabolism and to generate models that allow predictions of metabolic and physiological responses. Besides known sulphur-responsive genes derived from previous studies, numerous genes have been identified in transcriptomics studies. This has not only increased our knowledge of sulphur metabolism but has also revealed links between metabolic processes, thus indicating a previously unexpected complex interconnectivity. The identification of response and control networks has been supported through metabolomics and proteomics studies. Due to the complex interlacing nature of biological processes, experimental validation using targeted or systems approaches is ongoing. There is still room for improvement in integrating the findings from studies of metabolomes, proteomes, and metabolic fluxes into a single unifying concept and to generate consistent models. We therefore suggest a joint effort of the sulphur research community to standardize data acquisition. Furthermore, focusing on a few different model plant systems would help overcome the problem of fragmented data, and would allow us to provide a standard data set against which future experiments can be designed and compared.
A 21 cm pilot survey for pulsars and transients using the Focal L-Band Array for the Green Bank Telescope
Authors: Rajwade K M , Agarwal D , Lorimer D R , Pingel N M , Pisano D J , Ruzindana M , Jeffs B , Warnick K F , Roshi D A , McLaughlin M A 
Published: August 2019

Abstract
Phased array feed (PAF) receivers are at the forefront of modern day radio astronomy. PAFs are currently being developed for spectral line and radio continuum surveys and to search for pulsars and fast radio bursts. Here, we present results of the pilot survey for pulsars and fast radio bursts using the Focal plane L-band Array for the Green Bank Telescope (FLAG) receiver operating in the frequency range of 1.3–1.5 GHz. With a system temperature of ∼18 K, the receiver provided unprecedented sensitivity to the survey over an instantaneous field of view (FoV) of 0.1 deg2. For the survey, we implemented both time and frequency domain search pipelines designed to find pulsars and fast radio bursts that were validated by test pulsar observations. Although no new sources were found, we were able to demonstrate the capability of this instrument from observations of known pulsars. We report an upper limit on the rate of fast radio bursts above a fluence of 0.36 Jy ms to be 1.3 × 106 events per day per sky. Using population simulations, we show that the FLAG will find a factor of 2–3 more pulsars in same survey duration compared to its single pixel counterpart at the Green Bank Telescope. We also demonstrate that the new phased array receiver, ALPACA for the Arecibo telescope, will be a superior survey instrument and will find pulsars at a higher rate than most contemporary receivers by a factor of 2–10.
Exploring the M-dwarf Luminosity–Temperature–Radius relationships using Gaia DR2
Authors: Morrell Sam , Naylor Tim 
Published: August 2019

Abstract
There is growing evidence that M-dwarf stars suffer radius inflation when compared to theoretical models, suggesting that models are missing some key physics required to completely describe stars at effective temperatures less than about 4000 K. The advent of Gaia DR2 distances finally makes available large data sets to determine the nature and extent of this effect. We employ an all-sky sample, comprising of &gt;15 000 stars, to determine empirical relationships between luminosity, temperature, and radius. This is accomplished using only geometric distances and multiwave-band photometry, by utilizing a modified spectral energy distribution fitting method. The radii we measure show an inflation of $3\!-\!7{{\ \rm per\ cent}}$ compared to models, but no more than a $1\!-\!2{{\ \rm per\ cent}}$ intrinsic spread in the inflated sequence. We show that we are currently able to determine M-dwarf radii to an accuracy of $2.4{{\ \rm per\ cent}}$ using our method. However, we determine that this is limited by the precision of metallicity measurements, which contribute $1.7{{\ \rm per\ cent}}$ to the measured radius scatter. We also present evidence that stellar magnetism is currently unable to explain radius inflation in M-dwarfs.
The potassium absorption on HD189733b and HD209458b
Authors: Keles Engin , Mallonn Matthias , von Essen Carolina , Carroll Thorsten A , Alexoudi Xanthippi , Pino Lorenzo , Ilyin Ilya , Poppenhäger Katja , Kitzmann Daniel , Nascimbeni Valerio , Turner Jake D , Strassmeier Klaus G 
Published: August 2019

ABSTRACT
In this work, we investigate the potassium excess absorption around 7699 Å of the exoplanets HD189733b and HD209458b. For this purpose, we used high-spectral resolution transit observations acquired with the 2 × 8.4 m Large Binocular Telescope (LBT) and the Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI). For a bandwidth of 0.8 Å, we present a detection &gt;7σ with an absorption level of 0.18 per cent for HD189733b. Applying the same analysis to HD209458b, we can set 3σ upper limit of 0.09 per cent, even though we do not detect a K-excess absorption. The investigation suggests that the K feature is less present in the atmosphere of HD209458b than in the one of HD189733b. This comparison confirms previous claims that the atmospheres of these two planets must have fundamentally different properties.
Diversification of Retinoblastoma Protein Function Associated with Cis and Trans Adaptations
Authors: Mouawad Rima , Prasad Jaideep , Thorley Dominic , Himadewi Pamela , Kadiyala Dhruva , Wilson Nathan , Kapranov Philipp , Arnosti David N 
Published: August 2019

Abstract
Retinoblastoma proteins are eukaryotic transcriptional corepressors that play central roles in cell cycle control, among other functions. Although most metazoan genomes encode a single retinoblastoma protein, gene duplications have occurred at least twice: in the vertebrate lineage, leading to Rb, p107, and p130, and in Drosophila, an ancestral Rbf1 gene and a derived Rbf2 gene. Structurally, Rbf1 resembles p107 and p130, and mutation of the gene is lethal. Rbf2 is more divergent and mutation does not lead to lethality. However, the retention of Rbf2 >60 My in Drosophila points to essential functions, which prior cell-based assays have been unable to elucidate. Here, using genomic approaches, we provide new insights on the function of Rbf2. Strikingly, we show that Rbf2 regulates a set of cell growth-related genes and can antagonize Rbf1 on specific genes. These unique properties have important implications for the fly; Rbf2 mutants show reduced egg laying, and lifespan is reduced in females and males. Structural alterations in conserved regions of Rbf2 gene suggest that it was sub- or neofunctionalized to develop specific regulatory specificity and activity. We define cis-regulatory features of Rbf2 target genes that allow preferential repression by this protein, indicating that it is not a weaker version of Rbf1 as previously thought. The specialization of retinoblastoma function in Drosophila may reflect a parallel evolution found in vertebrates, and raises the possibility that cell growth control is equally important to cell cycle function for this conserved family of transcriptional corepressors.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Closure of Myelomeningocele Within 48 Hours to Decrease Infection Risk
Authors: Beier Alexandra D , Nikas Dimitrios C , Assassi Nadege , Bauer David F , Blount Jeffrey P , Durham Susan R , Flannery Ann Marie , Klimo Paul , McClung-Smith Catherine , Rehring Patricia , Tamber Mandeep S , Tyagi Rachana , Mazzola Catherine A 
Published: August 2019

Abstract

BACKGROUND
Appropriate timing for closure of myelomeningocele (MM) varies in the literature. Older studies present 48 h as the timeframe after which infection complication rates rise.

OBJECTIVE
The objective of this guideline is to determine if closing the MM within 48 h decreases the risk of wound infection or ventriculitis.

METHODS
The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full text articles were then reviewed and when appropriate, included in the evidentiary table. The class of evidence was evaluated, discussed, and assigned to each study that met inclusion criteria.

RESULTS
A total of 148 abstracts were identified and reviewed. A total of 31 articles were selected for full text analysis. Only 4 of these studies met inclusion criteria.

CONCLUSION
There is insufficient evidence that operating within 48 h decreases risk of wound infection or ventriculitis in 1 Class III study. There is 1 Class III study that provides evidence of global increase in postoperative infection after 48 h, but is not specific to wound infection or ventriculitis. There is 1 Class III study that provides evidence if surgery is going to be delayed greater than 48 h, antibiotics should be given.
The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-4.
BSCI-05. HOW MICROGLIA, BRAIN RESIDENT MYELOID CELLS, RESPOND TO BREAST CANCER METASTASIS INTO THE BRAIN?
Authors: Wojnicki Kamil , Kochalska Agata , Gieryng Anna , Czernicki Tomasz , Matyja Ewa , Kaminska Bozena 
Published: August 2019

Abstract
Brain metastasis from different cancers, including lung, breast, melanoma, colorectal or renal cell carcinoma is relatively common and its frequency increases with a prolonged survival of cancer patients. New anti-cancer therapies frequently fail to reduce metastatic burden. While the important role of tumor-associated macrophages as pro-tumorigenic cells facilitating tissue remodeling, invasion and metastasis is well documented, much less is known about the immune microenvironment of brain metastases and potential mechanisms that mediate interactions of cancer cells with brain immune cells - microglia. Triple-negative breast cancer metastases to the brain were discovered in 46% of patients. We evaluated the abundance and morphology of microglia on sections from breast cancer metastases using immunohistochemistry. We found that microglia cells are activated, surround the breast tumor cells and do not infiltrate the solid tumor. Searching for a potential attractant of microglia, we determined osteopontin levels in six human breast cancer cell lines and found upregulation of osteopontin in transformed cells, with the highest level in the triple-negative MDA-MB-231 cells. MDA-MB-231 cells activated primary murine microglia cultures when co-cultured. Invasion of MDA-MB-231 cells in co-cultures with murine immortalized BV2 microglial cells and human SV40 immortalized microglia was increased, as demonstrated using Matrigel Invasion Assay. Using immunofluorescence we detected osteopontin in cancer cells in human breast cancer metastases. Moreover, we found that minocycline, a clinically used antibiotic, reduces the osteopontin production in human breast cancer cells and the most sensitive cells were MDA-MB-231 cells. Our study shows that metastatic cancer cells may employ microglia to facilitate extravasation and colonization of brain parenchyma. We postulate that osteopontin mediates interactions between microglia and metastatic cancer cells and minocycline may interfere with those interactions. Funding: TEAM TECH CORE FACILITY FNP: Development of comprehensive diagnostics and personalized therapy in neuro-oncology
LPTO-09. INTRATHECAL TOPOTECAN FOR LEPTOMENINGEAL METASTASIS IN SOLID TUMORS: THE MD ANDERSON EXPERIENCE
Authors: Sinicrope Kaylyn D , Barata Pedro , Walker Julie , Tremont-Lukats Ivo W , Groves Morris , Loghin Monica , Seligman Christa , Ferguson Sherise , Weathers Shiao-Pei , Penas-Prado Marta , Kamiya-Matsuoka Carlos , Harrison Rebecca , Tummala Sudhakar , Trevino Christopher R , Peinado Shanta , Murthy Rashmi K , Seyedeh Dibaj , de Groot John , O’Brien Barbara 
Published: August 2019

Abstract
BACKGROUND: Leptomeningeal metastasis (LM) is a devastating complication of cancer resulting in progressive neurologic decline. Although intrathecal (IT) methotrexate and cytarabine are commonly used for solid tumor LM, we routinely use IT topotecan due to previously demonstrated similar efficacy and modest side effect profile. We report updated data on our experience. METHODS: We reviewed clinical records of patients with solid tumor LM treated with IT topotecan at MD Anderson Cancer Center from 2008–2018. Patient characteristics and course were summarized by descriptive statistics. Overall survival (OS) was estimated with Kaplan-Meier, and the association of KPS with OS evaluated with log-rank test. RESULTS: 138 patients were treated with IT topotecan. The median age was 54 years (range, 22–76), 81% were female. Breast cancer (62%) was the most common primary, then lung (21%), melanoma (4%). Median time from primary diagnosis to LM was 3.4 (range, 0.07–25.2) years. LM was diagnosed by CSF cytology alone in 8 (6%), MRI alone in 21 (15%), CSF+MRI in 108 (78%). Patients most commonly presented with headache (39%) or sensory changes (18%), and had a median KPS of 80 (range, 60–100). 66% had prior/concurrent brain metastasis. 71 patients (52%) received WBRT following LM diagnosis. 41% had adverse effects, most commonly nausea/vomiting (22%) and headache (20%). The majority were grade 1 (63%); 7 were grade 4 (2 Ommaya malfunctions and 5 infections). Patients received a median of 9 (range, 1–79) doses, most stopped due to CNS progression (42%). Median OS was 6.5 months (95% CI 4.7, 7.8). OS was 3.8 mos with KPS ≤70, vs. 7.5 mos with KPS &gt;70 (p&lt; 0.001). CONCLUSIONS: IT topotecan has a modest side effect profile. Patients with higher functional status at diagnosis had significantly better survival. This study supports the continued use of IT topotecan as a well-tolerated option for LM.
TRLS-07. BRAINSTORM: OUTCOMES FROM A MULTI-INSTITUTIONAL PHASE I/II STUDY OF RRx-001 IN COMBINATION WITH WHOLE BRAIN RADIATION THERAPY FOR PATIENTS WITH BRAIN METASTASES
Authors: Kim Michelle , Parmar Hemant , Schipper Matthew , Devasia Theresa , Aryal Madhava , Kesari Santosh , O’Day Steven , Morikawa Aki , Spratt Daniel , Junck Larry , Mammoser Aaron , Hayman James , Lawrence Theodore , Tsien Christina , Aiken Robert , Goyal Sharad , Abrouk Nacer , Trimble Malcolm , Cao Yue , Lao Christopher 
Published: August 2019

Abstract
INTRODUCTION: To determine the recommended Phase II dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases, and to assess whether quantitative changes in perfusion MRI after RRx-001 correlate with response. METHODS AND MATERIALS: Five centers participated in this phase I/II trial of RRx-001 given once pre-WBRT then twice weekly during WBRT (30 Gy/10 fractions). Four dose levels were planned (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, 27.5 mg/m2). Dose-escalation was managed by the Time-to-Event Continual Reassessment Model (TITE-CRM). Correlative DCE-MRI was performed in a subset of patients and linear mixed models used to correlate change in 24-hour T1, Ktrans (capillary permeability) and Vp (plasma volume) with change in tumor volume. RESULTS: Between 2015–2017, 31 patients were enrolled. Two patients dropped out prior to any therapy and 7 were treated with concurrent temozolomide following a study amendment. Median age was 60 years (range, 30–76) and 17 were male. The most common tumor types were melanoma (58%) and non-small cell lung cancer (20%). No dose-limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia in 6.9% (2/29). The median intracranial response rate was 46% (95%CI 24–68) and median overall survival was 5.2 months (95%CI 4.5–9.4). No neurologic deaths occurred. Among 10 evaluable patients undergoing DCE-MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 month and 4 months (p≤0.01). CONCLUSION: The addition of RRx-001 to WBRT is safe and well-tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, and in the absence of a dose response, the recommended Phase 2 dose is 10 mg administered twice weekly. A reduction in Vp by DCE-MRI 24 hours after RRx-001 suggests anti-angiogenic activity that is associated with longer-term tumor response.
OTHR-14. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING FET PET IN PATIENTS WITH MELANOMA AND LUNG CANCER BRAIN METASTASES: INITIAL EXPERIENCES
Authors: Galldiks Norbert , Abdulla Diana , Scheffler Matthias , Schweinsberg Viola , Schlaak Max , Kreuzberg Nicole , Landsberg Jenny , Lohmann Philipp , Ceccon Garry , Werner Jan-Michael , Celik Eren , Ruge Maximilian , Kocher Martin , Marnitz Simone , Fink Gereon , Langen Karl-Josef , Wolf Juergen , Mauch Cornelia 
Published: August 2019

Abstract
BACKGROUND: Due to the lack of specificity of contrast-enhanced (CE) MRI, both the response assessment and differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (ICI) or targeted therapy (TT) may be challenging, especially when ICI or TT is applied in combination with radiotherapy (RT). Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) as a problem-solving tool in comparison to CE-MRI in patients with brain metastases (BM) secondary to malignant melanoma (MM) and NSCLC. METHODS: We retrospectively identified 31 patients with 74 BM secondary to MM (n=20 with 42 BM) and NSCLC (n=11 with 32 BM) who underwent 52 FET-PET scans during the course of disease. All patients had RT prior to ICI or TT initiation (61%) or RT concurrent to ICI or TT (39%). In 13 patients, FET-PET was performed for treatment response assessment of ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET-PET was used for the differentiation of progression from PsP related to RT plus ICI or TT. In all BM, metabolic activity on FET-PET was evaluated by calculation of tumor/brain ratios. FET-PET imaging findings were compared to CE-MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. RESULTS: In 4 of 13 patients (31%), FET-PET provided additional information for treatment response evaluation beyond the information provided by CE-MRI alone. Furthermore, responding patients on FET-PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE-MRI findings suggesting progression, FET-PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. CONCLUSIONS: FET-PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with ICI or TT.
RADI-23. CLINICAL RISK ASSESSMENT SCORE TO ESTIMATE THE LIKELIHOOD OF PSEUDOPROGRESSION VERSUS TUMOR RECURRENCE FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Skeie Bente Sandvei , Enger Per Øyvind , Pedersen Paal-Henning , Skeie Geir Olve 
Published: August 2019

Abstract
OBJECTIVE: A major challenge in the follow-up of patients managed with stereotactic radiosurgery (SRS) for brain metastases (BM) is to differentiate pseudoprogression (PP) from tumor recurrence (TR). A clinical score based on tumor and treatment related factors would be valuable when selecting appropriate treatment. MATERIAL AND METHODS: Follow-up images of 97 consecutive patients treated with SRS for 406 BM were analyzed. Of these 100 (24.6 %) BM in 48 (49.5 %) patients responded either with TR (delayed growth; 53 (13.1 %) BM) or PP (temporary volume increase; 47 (11.6 %) BM). Differences between the 2 groups were analyzed and used to develop a PP risk assessment score (PP-RAS). RESULTS: Significant factors associated with a higher incidence of PP versus TR were: primary lung cancer vs. other primaries, BM volume ≤ 2cc (or BM ≤ 1.5 cm in diameter), Target cover ratio &gt; 98 % and prior radiation SRS or WBRT. Based on the presence (0) or not (1) of these 5 parameters, a risk assessment score for PP versus TR was established. A PP-RAS score of 0 corresponds with high likelihood of PP vs. TR, whereas a score of 5 corresponds with a high risk of TR. A score of ≤ 1 point was associated with 100 % PP, 2 points with 57 % PP and 43 % TR, 3 points with 57 % TR and 43 % PP, whereas ≥ 4 points were associated with 84 % TR and 16 % PP, π=24.57, df =4, p &lt; 0.001). CONCLUSION: Based on these 5 parameters at the time of SRS our risk assessment score could robustly differentiate between PP versus growth following SRS. The score is user-friendly and may be a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.