bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal form approach to global well-posedness of the quadratic derivative nonlinear Schrödinger equation on the circle
Authors: Guo Zihua , Kwon Soonsik , Oh Tadahiro , Chung Jaywan
Published: October 2016

We consider the quadratic derivative nonlinear Schrödinger equation (dNLS) on the circle. In particular, we develop an infinite iteration scheme of normal form reductions for dNLS. By combining this normal form procedure with the Cole–Hopf transformation, we prove unconditional global well-posedness in

L^{2}(\mathbb{T})

, and more generally in certain Fourier–Lebesgue spaces

\mathcal
{F}L^{s,p}(\mathbb{T})

, under the mean-zero and smallness assumptions. As a byproduct, we construct an infinite sequence of quantities that are invariant under the dynamics. We also show the necessity of the smallness assumption by explicitly constructing a finite time blowup solution with non-small mean-zero initial data.
Maternal Death Surveillance and Response Systems in driving accountability and influencing change
Authors: Bandali Sarah , Thomas Camille , Hukin Eleanor , Matthews Zoë , Mathai Matthews , Ramachandran Dilip Thandassery , Roos Nathalie , Lawley Ruth , Igado Oko , Hulton Louise
Published: October 2016

Good progress has been made in reducing maternal deaths from 1990–2015 but accelerated progress is needed to achieve the Sustainable Development Goals (SDGs) in ending preventable maternal deaths through a renewed focus on accountability and actions. This paper looks at how Maternal Death Surveillance and Response (MDSR) systems are strengthening response and accountability for better health outcomes by analyzing key findings from the WHO and UNFPA Global MDSR Implementation Survey across 62 countries. It examines two concrete examples from Nigeria and Ethiopia to demonstrate how findings can influence systematic changes in policy and practice. We found that a majority of countries have policies in place for maternal death notification and review, yet a gap remains when examining the steps beyond this, including reviewing and reporting at an aggregate level, disseminating findings and recommendations, and involving civil society and communities. As more countries move toward MDSR systems, it is important to continue monitoring the opportunities and barriers to full implementation, through quantitative means such as the Global MDSR Implementation Survey to assess country progress, but also through more qualitative approaches, such as case studies, to understand how countries respond to MDSR findings.
Using advocacy and data to strengthen political accountability in maternal and newborn health in Africa
Authors: ten Hoope‐Bender Petra , Martin Hilber Adriane , Nove Andrea , Bandali Sarah , Nam Sara , Armstrong Corinne , Ahmed Mohammed Ahmed  , Chatuluka Mathias G. , Magoma Moke , Hulton Louise
Published: October 2016

Accountability mechanisms help governments and development partners fulfill the promises and commitments they make to global initiatives such as the Millennium Development Goals and the Global Strategy on Women's and Children's health, and regional or national strategies such as the Campaign for the Accelerated Reduction in Maternal Mortality in Africa (CARMMA). But without directed pressure, comparative data and tools to provide insight into successes, failures, and overall results, accountability fails. The analysis of accountability mechanisms in five countries supported by the Evidence for Action program shows that accountability is most effective when it is connected across global and national levels; civil society has a central and independent role; proactive, immediate and targeted implementation mechanisms are funded from the start; advocacy for accountability is combined with local outreach activities such as blood drives; local and national champions (Presidents, First Ladies, Ministers) help draw public attention to government performance; scorecards are developed to provide insight into performance and highlight necessary improvements; and politicians at subnational level are supported by national leaders to effect change. Under the Sustainable Development Goals, accountability and advocacy supported by global and regional intergovernmental organizations, constantly monitored and with commensurate retribution for nonperformance will remain essential.
OS3 - 187 Differentiating Radionecrosis from Tumor Progression Using IVIM perfusion Fraction in Brain Metastases Treated with Radiosurgery
Authors: Detsky J , Conklin J , Keith J , Symons S , Sahgal A , Heyn C , Soliman H
Published: October 2016

Radiation necrosis occurs in 5-25% of patients who undergo stereotactic radiosurgery (SRS) for brain metastases. Intravoxel incoherent motion (IVIM) uses MRI diffusion-weighted imaging (DWI) to assess regional perfusion. We investigated the utility of IVIM to differentiate recurrent tumor from radionecrosis after SRS. Patients who had SRS and subsequent surgical resection of what was thought to be either tumor progression or necrosis were included. ROIs were contoured on the pre-operative post-Gd T1-weighted images and transferred to DWI images using automated co-registration. The perfusion fraction (f) was calculated using asymptotic fitting and the mean f (fmean), 90th percentile for f (f90), mean ADC (ADCmean) and 10th percentile for ADC (ADC10) were calculated. Pathology reports were used to identify the predominant feature (necrosis versus tumor). Nine patients with ten lesions were included. One lesion exhibited pure necrosis while the other nine were mixed; three were predominantly (>75%) tumor, three predominantly necrosis, and three were equal parts of both. The perfusion fraction was significantly higher in cases with predominantly tumor compared to those with predominantly necrosis (fmean 0.10±0.01 vs 0.08±0.01, p=0.02 and f90 0.22±0.01 vs 0.14±0.02, p<0.001). ADC did not differentiate tumor from necrosis (ADCmean 0.97±0.23 vs 1.02±0.36, p=0.8 and ADC10 0.53±0.29 vs 0.76±0.29, p=0.33). The IVIM perfusion fraction is useful in differentiating recurrent tumor from radionecrosis in brain metastases treated with SRS. This is the first study to evaluate IVIM against the gold standard (histopathology).
OS10 - 147 Tumor-Associated Astrocytes Promote Glioma Invasion via Cx43
Authors: Sin W. C , Hong X , Bechberger J , Naus C.C
Published: October 2016

Although genetic mutations are usually responsible for the initial tumor formation and progression, changes in the microenvironment also have a critical role in facilitating this process. Many ''untransformed'' cells infiltrate the tumors, and recent evidence suggests cancer cells can ‘reprogram’ normal cells by miRNAs, which are small, non-coding RNA molecules that regulate several protein targets. One prominent feature of glioma pathology is massive gliosis, an inflammatory response consisting of reactive astrocytes, in and around the tumor. We show that expression of Cx43, a major gap junction protein in astrocytes, is significantly enhanced in astrocytes at the tumor border. Using a mouse model consisting of syngeneic intracranial implantation of GL261 glioma cells into Nestin-Cre:Cx43fl/fl mice in which Cx43 is selectively eliminated in astrocytes, we demonstrate that reduction of astrocytic Cx43 decreases the dissemination of glioma cells from the tumor core. Similarly, knocking down Cx43 in astrocytes also reduces glioma invasion in a co-culture of glioma cells and astrocytes. By comparing the microRNA profiles of the astrocytes before and after co-culture with human glioma cells, we have identified a miR-5096 that appears to reprogram astrocytes to enhance the invasiveness of glioma cells. We are now examining whether we can prevent glioma cells from invading the brain and establishing recurrent secondary tumors by stopping the exchange of materials between glioma cells and astrocytes through eliminating Cx43 channel activity.
PS1 - 127 A Mixed Method Study of a Peer Support Intervention for Newly Diagnosed Primary Brain Tumour Patients
Authors: Cashman R.
Published: October 2016

The purpose of this study was to investigate the impact of an intervention designed to support newly diagnosed primary brain tumour patients. The intervention involved a structured, one time meeting between newly diagnosed patients and trained volunteer “veteran” primary brain tumour patients. Methods Two trained volunteers met for a single, face to face meeting on an individual basis with a total of 10 newly diagnosed patients. A combination of questionnaires and interviews were used to investigate the impact of the intervention for the new patients and the volunteers. Results: The intervention appeared to be of substantial value for both groups of participants. Analysis revealed that the newly diagnosed patients experienced a range of benefits, including those related to the themes of: increased hope; valued guidance; hearing what it’s really like; overcoming aloneness; and realignment of priorities. Veteran patients experienced a sense accomplishment and decreased anxiety as a result of the intervention. Only minor adverse effects and challenges were reported. Conclusions The findings provide initial evidence that the experimental intervention has the potential to be a safe, effective means of promoting psycho-social well-being in newly diagnosed patients and may also have positive effects for veteran patients. Further investigation into the use of one to one, peer support for brain tumour patients is an important research priority.
PS1 - 169 Discovering the Treatment Refractory BTIC Population in Group 3 Medulloblastoma through Therapy Adapted Patient-Derived Human Mouse Xenograft (PDX) Model
Authors: Bakhshinyan D. , Vijayakumar T. , Manoranjan B. , McFarlane N. , Venugopal C. , Singh M. , Qazi M. , Vora P. , Singh S.
Published: October 2016

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is categorized into four molecular subgroups. Given the high rate of metastatic dissemination at diagnosis and recurrence in Group 3 MBs, these patients have the worst clinical outcome with a 5-year survivorship of approximately 50%. By adapting the existing COG (Children’s Oncology Group) Protocol for children with newly diagnosed high-risk MB, for treatment of immuno-deficient mice intracranially engrafted with human MB brain tumour initiating cells we aim to identify and characterize the treatment-refractory cell population in Group 3 MBs. Mice were sacrificed at multiple time points during the course of tumor development and therapy: (i) at engraftment; (ii) post-radiation; (iii) post-radiation and chemotherapy; and (iv) at MB recurrence. MB cell populations recovered separately from brains and spines were comprehensively profiled for gene expression analysis, stem cell and molecular features to generate a global, comparative profile of MB cells through therapy. We report a higher expression of CD133, Sox2 and Bmi1 in addition to increased self-renewal capacity following chemoradiotherapy treatment. The enrichment map constructed from global gene expression analysis showed an increase in pathways regulating self-renewal, DNA repair and chemoresistance post-therapy despite the apparent decrease in tumour size and vascularity. Additionally, from gene expression at MB recurrence, we identified a list of genes that negatively correlate with survival in patients diagnosed with Group 3 MB. A differential genomic profile of the “treatment-responsive” tumors against those that fail therapy may contribute to discovery of novel therapeutic approaches for the most aggressive subgroup of MB.
PS1 - 170 Bmi1 is a Therapeutic Target in Recurrent Childhood Medulloblastoma
Authors: Garg N. , Bakhshinyan D. , Manoranjan B. , Venugopal C. , Hallett R. , Mahendram S. , Vijayakumar T. , Subapanditha M. , Qazi M. , Singh M. , McFarlane N. , Mann A. , Vora P. , Davis T. , Singh S.
Published: October 2016

Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
PS2 - 167 CIC Deficiency is Associated with Dysregulation of Genes Involved in Cell Adhesion and Developmental Processes
Authors: LeBlanc V.G. , Chittaranjan S. , Firme M. , Chan S.Y. , Song J. , Lee A. , Yip S. , Marra M.A.
Published: October 2016

Somatic mutations in the Capicua (CIC) gene were first identified in Type I low-grade gliomas (LGGs), which are characterized by 1p/19q co-deletions and IDH mutations. They are found at frequencies of ~50-70% in this glioma subtype, and have since been identified in ~40% of stomach adenocarcinomas (STADs) of the microsatellite instability (MSI) subtype; however, the role of these somatic mutations in malignancy has yet to be established. In Drosophila, CIC functions as a transcriptional repressor whose activity is inhibited upon activation of the mitogen-activated protein kinase (MAPK) signalling pathway. Though mammalian CIC appears to retain these functions, only three of its target genes have been established in human cells: ETV1, ETV4, and ETV5 (ETV1/4/5). To further probe CIC’s transcriptional network, we developed CIC knockout cell lines and performed transcriptomic and proteiomic analyses in these and in control cell lines expressing wild type CIC, identifying a total of 582 differentially expressed genes. We also used RNA-seq data from The Cancer Genome Atlas (TCGA) for Type I LGGs and STADs to perform additional differential expression analyses between CIC-deficient and CIC-expressing samples. Though gene-level overlap was limited between the three contexts, we found that CIC appears to regulate the expression of genes involved in cell-cell adhesion, metabolism, and developmental processes in all three contexts. These results shed light on the pathological role of CIC mutations and may help explain why these have been associated with poorer outcome within Type I LGGs.
PS2 - 172 Preclinical Validation of a Novel CD33/CD3 Bispecific T-Cell Engager (BiTE) Antibody to Target Patient-Derived Glioblastoma Cells
Authors: Vora P. , Venugopal C. , Choksi C. , Qazi M. , Adams J. , London M. , Subapanditha M. , Singh M. , Bakshinyan D. , Sidhu S. , Moffat J. , Singh S.
Published: October 2016

Glioblastoma (GBM), an aggressive primary adult brain tumor, is feared for its near uniformly fatal prognosis. Despite the use of aggressive treatment including surgical resection, radiotherapy and chemotherapy, the outcome of patients with GBM has failed to improve significantly. Numerous studies have implicated CD133+GBM subpopulation as driver of chemo- and radio-resistance. CD133 expression correlates with disease progression, recurrence, and poor overall survival of GBM patients. Here, we describe the preclinical evaluation of a recombinant CD133xCD3 bispecific T-cell engager (BiTE) antibody that redirects human polyclonal T cells to CD133+GBM cells, inducing very potent anti-tumor response. CD133-specific BiTE was constructed; with one arm recognizing the tumor antigen (CD133) while the second is specific to CD3 antigen. Using CD133high and CD133low primary GBM lines, we validated the binding of BiTEs to CD133+GBMs and CD3+T cells. In order to test the ability of BiTEs to functionally elicit CD133-specific cytotoxic responses in vitro, we performed killing assays. We observed CD133-specific BiTE mediated T cell activation and redirection to kill CD133-expressing GBM cells in a co-culture of T cells and GBM cells. The killing was more efficient in CD133high GBMs compared to CD133low GBMs, validating its specificity to target CD133+BTICs. Treatment with BiTEs yielded significant reductions in brain tumor burden in vivo. These data offers compelling evidence that BiTE-mediated cytotoxicity against treatment-resistant CD133+GBMs could provide a very potent, specific and can be a novel therapeutic strategy for GBM patients.
PS2 - 178 Brevican-Specific Peptides for the Development of Next-Generation Targeted Theranostics for High Grade Gliomas
Authors: Cho C.F. , Kasai K. , Wolfe J. , Hornburg K. , Bononi F. , Luyt L. , Pentelute B. , Viapiano M. , Chiocca E.A. , Lawler S.
Published: October 2016

High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of improved theranostic agents leading to better detection methods, as well as safer anti-cancer therapies. Brevican (Bcan), a CNS-specific protein is upregulated in glioma cells and correlates with tumor progression. Particularly, a Bcan isoform lacking normal glycosylation, called B/bDg is a unique glioma marker and is not expressed in non-cancerous tissues. Therefore, B/bDg represents a valuable target for anti-cancer strategies. We describe here the discovery of novel high-affinity B/bDg-targeted peptides using rapid combinatorial library screening approaches and a microfluidic sorting device of our own design. Briefly, a one-bead-one-compound (OBOC) peptide library was screened against small magnetic particles decorated with B/bDg. Positive “hit” beads labeled with magnetic particles were isolated using an inexpensive but yet, accurate and high-throughput in-house microfluidic magnetic-activated sorter. These hits were exposed to cells expressing B/bDg, and beads with the highest cell association were isolated and sequenced. Seven novel peptides were identified. Cell uptake analyses and blocking studies revealed that 5 of these peptides displayed specific uptake in B/bDg-overexpressing cells. These candidates displayed nano-/micromolar binding affinity for recombinant B/bDg protein. Further analyses of these candidates using confocal microscopy revealed increased peptide binding/uptake in patient-derived glioma stem cells (GSCs) compared with primary human astrocytes. We plan to incorporate these onto multi-functional BBB-penetrating nanoparticles loaded with imaging agents or a drug payload to translate them into highly selective and efficacious brain cancer theranostic agents.
PC3 - 152 Impact of Extent of Resection Upon Outcome in Newly Diagnosed Glioblastoma: A Study in the Molecular Era
Authors: Sayeed W.M.H. , Batuyong E. , Easaw J.C. , Pitz M. , Kelly J.J.P.
Published: October 2016

For decades, debate has persisted regarding the role of surgical resection in newly diagnosed glioblastoma. There is increasing evidence that extent of resection (EoR) is an independent prognostic factor. Previous work has proposed the inclusion of EoR in a risk stratification algorithm but does not incorporate account recent advances in the molecular characterization of tumours. We set out to investigate the effect of EoR on overall survival (OS), and to develop a stratification algorithm incorporating both EoR and modern molecular markers for prognostication. HYPOTHESIS: Greater EoR is independently associated with improved OS. METHODS: We examined 190 consecutive cases of histopathologically confirmed newly-diagnosed glioblastoma who were operated upon between January 1, 2012 and December 31, 2014. Variables including age, sex, postal code, KPS, tumour location, presenting symptoms, treatment history, date of progression, date of reoperation, as well as MGMT, IDH, 1p/19q codeletion, and ATRX status were recorded. Preoperative and postoperative MRIs were reviewed and volumetric tumour burden will be analyzed and EoR will be calculated. RESULTS: Preliminary EoR calculations (n=18) show a positive correlation between EoR and OS. CONCLUSION: A correlation exists between EoR and OS, although multivariable analysis is planned to exclude potential confounders. MRI review, chart review including molecular marker analysis and EoR calculations are ongoing.
PC3 - 154 Phase I/II Study of VAL-083 in Patients with Recurrent Glioblastoma
Authors: Shih K.C. , Patel M.R. , Butowski N. , Falchook G.S. , Kizilbash S.H. , Bacha J.A. , Brown D.M. , Steino A. , Schwartz R. , Kanekal S. , Lopez L.M. , Burris H.A.
Published: October 2016

Glioblastoma (GBM) is the most common brain cancer. Resistance to front-line systemic therapy with temozolomide (TMZ) is correlated with O6-methylguanine-DNA-methyltransferase (MGMT) expression. Second-line treatment with bevacizumab has not improved overall survival. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that has MGMT-independent cell-kill activity against GBM cell-lines and cancer stem cells in vitro. VAL-083 crosses the blood-brain barrier and showed promise against CNS tumors in prior NCI-sponsored clinical trials. The goal of this clinical trial is to determine appropriate VAL-083 dosing for advancement to Phase III trials as a new treatment for recurrent GBM. METHODS: Patients must have recurrent GBM following surgery, radiation, TMZ and bevacizumab. Phase I: Open-label, single-arm, dose-escalation study. Patients received VAL-083 on days 1,2,3 of a 21-day cycle, until reaching MTD. Phase II: Additional patients enrolled at MTD to further assess safety and outcomes. RESULTS: Phase I: 29 patients were enrolled across 9 dose cohorts (1.5-50 mg/m2/d). 40mg/m2/d was confirmed as MTD. Myelosuppression was mild; no drug-related serious adverse events were reported at doses up to 40mg/m2/d. Dose limiting G4 thrombocytopenia was observed at higher doses. Platelet nadir occurred around day 20 and resolved rapidly and spontaneously. A dose-related survival improvement was observed. Pharmacokinetic analyses show 1-2h plasma terminal half-life; average Cmax 781ng/mL at 40mg/m2/d. Phase II: 14 patients were enrolled at 40mg/m2/d. To date, safety observations in Phase II are consistent with Phase I. CONCLUSIONS: VAL-083 at 40mg/m2/d exhibits a favorable safety profile and dose-related trend toward clinically meaningful improved survival in refractory GBM patient
PC3 - 190 Impact of Functional Magnetic Resonance Imaging on Clinical Decision Making and Outcomes in Patients with Low Grade Gliomas
Authors: Kosteniuk E. , Lau J.C. , Megyesi J.F.
Published: October 2016

This study aims to evaluate the impact of preoperative functional magnetic resonance imaging (fMRI) on low grade glioma (LGG) patients’ outcomes and surgical planning. Methods In this retrospective matched cohort study of a single surgeon’s patients, we are comparing two groups of LGG patients (WHO grade II) based on exposure to fMRI. Sixteen LGG patients who underwent fMRI were selected, and 32 control (non-fMRI exposed) patients are being selected through propensity score matching from a pool of 764 brain tumour patients. To assess the impact of fMRI data on clinicians’ decision making process, neurosurgeons within a single centre are completing questionnaires regarding treatment options for each LGG fMRI patient based on clinical data and structural imaging before and after fMRI. Results Within the group of 16 LGG patients who have undergone fMRI studies over a 12-year period, most patients presented with seizures (81 percent), and most lesions were left-sided (81 percent) and frontal (75 percent). Patients underwent either craniotomy (50 percent), stereotactic biopsy (25 percent) or nonsurgically management (25 percent). In surgical patients, between presurgical assessment and eight week post-surgical follow-up, mean modified Rankin scale improved from 1.80 (sd 0.79) to 1.50 (sd 0.97). In our cohort, 5-year mortality was 12.5 percent (mean follow-up duration 5.46 years). Conclusions Data analysis is ongoing with plans to compare relevant patient demographics and outcomes, and to analyse questionnaires to elucidate how surgeons incorporate fMRI data into their therapeutic approach.
PC3 - 219 Evaluation of delayed FDG-PET in differentiating progressive disease from post-treatment radiation effect in brain tumors
Authors: Harrison R.A. , Masood A. , Mawlawi O. , Schellingerhout D. , Chasen B.A. , Millican R. , Li J. , O’Brien B.J. , Johnson J.M.
Published: October 2016

Traditional and advanced magnetic resonance imaging techniques are often unable to differentiate progressive central nervous system neoplasm from post-treatment radiation effect (PTRE). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with delayed imaging has been shown to increase the specificity of PET imaging for cerebral neoplasm in small studies. We sought to further evaluate the potential diagnostic benefits of delayed imaging at 5 hours versus standard imaging at 1 hour to differentiate progressive disease (PD) from PTRE in patients with primary or metastatic brain tumors treated with radiation therapy.

Ten patients with primary (n=4) and metastatic (n=6) brain tumors were identified, with diagnostic confirmation of PD or PTRE provided by pathology or>3 month clinical and radiographic follow-up. Maximum standard uptake values (SUV) were calculated for suspicious areas of abnormal contrast enhancement (lesion) and compared to contralateral normal appearing brain (background) at both early and delayed time points. Seven patients were classified as having PD and 3 as having PTRE based pathology or clinical/radiographic follow up. The average lesion to background ratio (L/B) at the early time point (1.16+0.50) was significantly different than L/B for the later time point (1.72+1.10), p=0.030. The mean L/B for PD was 2.17+1.01 at the later time point compared to 0.65+0.06 for PTRE (p=0.010). For the earlier time point, L/B for PD was 1.40+0.42, compared to the L/B for PTRE which was 0.61+0.10 (p=0.003).L/B ratios at early and delayed time points successfully differentiated between patients with PD and PTRE, with significantly greater L/B ratios seen at delayed time points. These initial results are promising and further investigation is underway to evaluate the contribution of delayed imaging in differentiating PD from PTRE.
The interaction of a rising bubble and a particle in oscillating fluid
Authors: Lyubimov D. V. , Klimenko L. S. , Lyubimova T. P. , Filippov L. O.
Published: October 2016

This article considers the interaction of a rising bubble and a sedimenting fine particle in an incompressible viscous liquid under vibrations (ultrasound). The particle is subject to Stokes, Basset and buoyancy forces, and average force due to the inhomogeneity of the pulsating field. It is shown that the main contribution to the average force is made by interference of the external field and the field caused by the monopole mode of bubble oscillations. The interaction force is the attraction of the particle to the bubble. It is found that even weak vibrations lead to considerable increase of the effective cross-section of particle capture by the bubble. The evaluation of the efficiency of the flotation process exposed to an ultrasound action is discussed.
Why spheroids orient preferentially in near-wall turbulence
Authors: Zhao Lihao , Andersson Helge I.
Published: October 2016

Non-spherical particles are known to orient preferentially in near-wall turbulence, but rod-like and disk-like particles align themselves differently relative to the mean vorticity direction. To uncover the mechanism that gives rise to such preferential particle orientations in anisotropic turbulence, Lagrangian statistics from a channel-flow simulation have been analysed. Ni et al. (J. Fluid Mech., vol. 743, 2014, R3) showed that the fluid vorticity and long rods independently aligned with the Lagrangian fluid stretching direction in isotropic turbulence. Following their approach, we deduced the left Cauchy–Green strain tensor along Lagrangian trajectories of tracer spheroids in channel-flow turbulence. The results showed that the alignment of the fluid vorticity vector with the strongest Lagrangian stretching direction in the channel centre, just as in isotropic turbulence, vanished in the vicinity of the walls. The analysis revealed that the directions of the strongest Lagrangian stretching and compression in near-wall turbulence are in the streamwise and wall-normal directions, respectively. All over the channel we found that the symmetry axis of prolate spheroids aligned with the direction of strongest Lagrangian stretching whereas oblate spheroids oriented with the direction of Lagrangian compression. This finding is apparently universal since the same trends were found in highly anisotropic wall turbulence as well as in isotropic turbulence. Contrary to the prevailing view, we have shown for the first time that the preferential orientation of the symmetry axis of long rods in the streamwise direction and of flat disks in the wall-normal direction is caused by Lagrangian stretching and not by fluid rotation. This finding fills a gap in our understanding of orientation and rotation of tracer spheroids in anisotropic wall turbulence.
Flow dynamics and enhanced mixing in a converging–diverging channel
Authors: Gepner S. W. , Floryan J. M.
Published: October 2016

An analysis of flows in converging–diverging channels has been carried out with the primary goal of identifying geometries which result in increased mixing. The model geometry consists of a channel whose walls are fitted with spanwise grooves of moderate amplitudes (up to 10 % of the mean channel opening) and of sinusoidal shape. The groove systems on each wall are shifted by half of a wavelength with respect to each other, resulting in the formation of a converging–diverging conduit. The analysis is carried out up to Reynolds numbers resulting in the formation of secondary states. The first part of the analysis is based on a two-dimensional model and demonstrates that increasing the corrugation wavelength results in the appearance of an unsteady separation whose onset correlates with the onset of the travelling wave instability. The second part of the analysis is based on a three-dimensional model and demonstrates that the flow dynamics is dominated by the centrifugal instability over a large range of geometric parameters, resulting in the formation of streamwise vortices. It is shown that the onset of the vortices may lead to the elimination of the unsteady separation. The critical Reynolds number for the vortex onset initially decreases as the corrugation amplitude increases but an excessive increase leads to the stream lift up, reduction of the centrifugal forces and flow stabilization. The flow dynamics under such conditions is again dominated by the travelling wave instability. Conditions leading to the formation of streamwise vortices without interference from the travelling wave instability have been identified. The structure and the mixing properties of the saturated states are discussed.
Formation of Supermassive Black Hole Seeds
Authors: Latif Muhammad A. , Ferrara Andrea
Published: October 2016

The detection of quasars at z > 6 unveils the presence of supermassive black holes of a few billion solar masses. The rapid formation process of these extreme objects remains a fascinating and open issue. Such discovery implies that seed black holes must have formed early on, and grown via either rapid accretion or BH/galaxy mergers. In this theoretical review, we discuss in detail various BH seed formation mechanisms and the physical processes at play during their assembly. We discuss the three most popular BH formation scenarios, involving the (i) core-collapse of massive stars, (ii) dynamical evolution of dense nuclear star clusters, (iii) collapse of a protogalactic metal free gas cloud. This article aims at giving a broad introduction and an overview of the most advanced research in the field.
Dietary fish protein hydrolysates containing bioactive motifs affect serum and adipose tissue fatty acid compositions, serum lipids, postprandial glucose regulation and growth in obese Zucker fa/fa rats
Authors: Drotningsvik Aslaug , Mjøs Svein A. , Pampanin Daniela M. , Slizyte Rasa , Carvajal Ana , Remman Tore , Høgøy Ingmar , Gudbrandsen Oddrun A.
Published: October 2016

The world’s fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chainn-3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA andn-3:n-6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more totaln-3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.
UPLAND RICE CULTIVAR RESPONSES TO ROW SPACING AND WATER STRESS ACROSS MULTIPLE ENVIRONMENTS
Authors: HEINEMANN ALEXANDRE BRYAN , RAMIREZ-VILLEGAS JULIAN , NASCENTE ADRIANO STEPHAN , ZEVIANI WALMES MARQUES , STONE LUÍS FERNANDO , SENTELHAS PAULO CESAR
Published: October 2016

Upland rice (Oryza sativa L., UR) could be an option under soybean–maize crop rotation system. However, the recommended row spacing for UR (0.30 m) is shorter than that recommended for soybean and corn (0.40 m), limiting the use of UR in this rotation. We hypothesize that cultivar adaptation to wider than recommended row spacing and local environmental conditions harbour significant potential for overcoming the yield constraints of wider row spacing. We evaluated the row spacing effects on rice grain yield and their components in UR cultivars grown under different water deficit conditions. The experiments were designed as a randomized block in a split–split-plot scheme with sites (the cities of Santo Antônio de Goiás, Porangatu and Formoso) as main plots, row spacing (0.25, 0.35, 0.45 and 0.55 m) as the subplots and UR cultivars (one old and two modern genotypes) as the sub-subplots. We found that, in the less stressful environments, the modern cultivars, BRSMG Curinga and BRS Primavera, presented the highest grain yield. By contrast, in environments with moderate to intense water stress, the traditional cultivar, Douradão, presented the best performance, regardless of row spacing used. We conclude that UR is a viable option for soybean–maize rotation systems, as the UR cultivars tested presented no noticeable yield losses when sown with the same row spacing used for soybean and maize crops (0.40 m). In terms of impact, it can lead to an increase in UR cropped area in Brazil, and decrease in dependence on flooded rice harvested in the south of the country.
Cambrian–Ordovician conodonts from slump deposits of the Argentine Precordillera: new insights into its passive margin development
Authors: VOLDMAN GUSTAVO G. , ALONSO JUAN L. , FERNÁNDEZ LUIS P. , BANCHIG ALDO L. , ALBANESI GUILLERMO L. , ORTEGA GLADYS , CARDÓ RAÚL
Published: October 2016

The Los Sombreros Formation represents the western continental margin slope deposits of the Argentine Precordillera, a sub-terrane accreted to Gondwana as part of the Cuyania Terrane in early Palaeozoic times. The age of these gravity-driven deposits is controversial and, therefore, a precise biostratigraphic scheme is essential to reveal the evolution of the continental margin. New conodont samplings along with sedimentological and structural analysis carried out in the Los Sombreros Formation in the La Invernada Range provide clues to its depositional framework. The sedimentary succession is made up of dominantly calciturbidites, carbonate breccias and conglomerates, along with mudstones that represent the pelagic/hemipelagic background sedimentation. It displays hectometric to outcrop-scale slump folds with variable hinge-line orientations and pinch-and-swell structures, evidencing soft-sediment deformation, consistent with a slope to base-of-slope setting. Three limestone samples from this succession include conodonts referable to the pandemicHirsutodontus simplexSubzone of theCordylodus intermediusZone (upper Furongian, Cambrian) and from theMacerodus dianaeZone (upper Tremadocian, Ordovician), implying that a slope connected the shallow-water shelf with a deep-water (oceanic) basin at least since late Cambrian times. The conodont faunas show affinities to coeval assemblages from outer shelf and slope environments around Laurentia yet they are not conclusive to postulate a geographic origin for the Precordillera. The thermal alteration of the conodonts is consistent with sedimentary burial and nappe stacking in this sector of the Precordillera.
Epidemiology of restaurant-associated foodborne disease outbreaks, United States, 1998–2013
Authors: ANGELO K. M. , NISLER A. L. , HALL A. J. , BROWN L. G. , GOULD L. H.
Published: October 2016

Although contamination of food can occur at any point from farm to table, restaurant food workers are a common source of foodborne illness. We describe the characteristics of restaurant-associated foodborne disease outbreaks and explore the role of food workers by analysing outbreaks associated with restaurants from 1998 to 2013 reported to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System. We identified 9788 restaurant-associated outbreaks. The median annual number of outbreaks was 620 (interquartile range 618–629). In 3072 outbreaks with a single confirmed aetiology reported, norovirus caused the largest number of outbreaks (1425, 46%). Of outbreaks with a single food reported and a confirmed aetiology, fish (254 outbreaks, 34%) was most commonly implicated, and these outbreaks were commonly caused by scombroid toxin (219 outbreaks, 86% of fish outbreaks). Most outbreaks (79%) occurred at sit-down establishments. The most commonly reported contributing factors were those related to food handling and preparation practices in the restaurant (2955 outbreaks, 61%). Food workers contributed to 2415 (25%) outbreaks. Knowledge of the foods, aetiologies, and contributing factors that result in foodborne disease restaurant outbreaks can help guide efforts to prevent foodborne illness.
ON THE MACROECONOMIC AND WEALTH EFFECTS OF UNCONVENTIONAL MONETARY POLICY
Authors: Jawadi Fredj , Sousa Ricardo M. , Traverso Raffaella
Published: October 2016

This paper focuses on the macroeconomic and wealth effects of unconventional monetary policy. To this end, we estimate a Bayesian structural vector autoregression (B-SVAR) using U.S. monthly data for the post-Lehman Brothers' collapse period. We show that a positive shock to the growth rate of central bank reserves does not have a substantial impact on industrial production or consumer prices. However, it also gives a strong boost to asset prices, which is larger in magnitude for stock prices than for housing prices. Thus, unconventional monetary policy typically operates via portfolio-rebalancing effects. A VAR counterfactual exercise confirms the role of the shocks to the growth rate of central bank reserves in explaining the dynamics of the variables included in the system, especially in the case of asset prices. Finally, additional empirical assessments uncover an important change in the conduct of monetary policy from “standard” to “exceptional” times and the suitability of our model to capture such a structural transformation.
Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation
Authors: Beyer Sophie , Pontis Julien , Schirwis Elija , Battisti Valentine , Rudolf Anja , Le Grand Fabien , Ait-Si-Ali Slimane
Published: October 2016

The histone 3 lysine 9 methyltransferase Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on the roles of Setdb1 in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation. Ex vivo studies on isolated single myofibres showed that Setdb1 is required for adult muscle stem cells expansion following activation. In vitro studies in skeletal myoblasts confirmed that Setdb1 suppresses terminal differentiation. Genomic binding analyses showed a release of Setdb1 from selected target genes upon myoblast terminal differentiation, concomitant to a nuclear export of Setdb1 to the cytoplasm. Both genomic release and cytoplasmic Setdb1 relocalisation during differentiation were dependent on canonical Wnt signalling. Transcriptomic assays in myoblasts unravelled a significant overlap between Setdb1 and Wnt3a regulated genetic programmes. Together, our findings revealed Wnt-dependent subcellular relocalisation of Setdb1 as a novel mechanism regulating Setdb1 functions and myogenesis.
Early cave art and ancient DNA record the origin of European bison
Authors: Soubrier Julien , Gower Graham , Chen Kefei , Richards Stephen M. , Llamas Bastien , Mitchell Kieren J. , Ho Simon Y. W. , Kosintsev Pavel , Lee Michael S. Y. , Baryshnikov Gennady , Bollongino Ruth , Bover Pere , Burger Joachim , Chivall David , Crégut-Bonnoure Evelyne , Decker Jared E. , Doronichev Vladimir B. , Douka Katerina , Fordham Damien A. , Fontana Federica , Fritz Carole , Glimmerveen Jan , Golovanova Liubov V. , Groves Colin , Guerreschi Antonio , Haak Wolfgang , Higham Tom , Hofman-Kamińska Emilia , Immel Alexander , Julien Marie-Anne , Krause Johannes , Krotova Oleksandra , Langbein Frauke , Larson Greger , Rohrlach Adam , Scheu Amelie , Schnabel Robert D. , Taylor Jeremy F. , Tokarska Małgorzata , Tosello Gilles , van der Plicht Johannes , van Loenen Ayla , Vigne Jean-Denis , Wooley Oliver , Orlando Ludovic , Kowalczyk Rafał , Shapiro Beth , Cooper Alan
Published: October 2016

The two living species of bison (European and American) are among the few terrestrial megafauna to have survived the late Pleistocene extinctions. Despite the extensive bovid fossil record in Eurasia, the evolutionary history of the European bison (or wisent,Bison bonasus) before the Holocene (<11.7 thousand years ago (kya)) remains a mystery. We use complete ancient mitochondrial genomes and genome-wide nuclear DNA surveys to reveal that the wisent is the product of hybridization between the extinct steppe bison (Bison priscus) and ancestors of modern cattle (aurochs,Bos primigenius) before 120 kya, and contains up to 10% aurochs genomic ancestry. Although undetected within the fossil record, ancestors of the wisent have alternated ecological dominance with steppe bison in association with major environmental shifts since at least 55 kya. Early cave artists recorded distinct morphological forms consistent with these replacement events, around the Last Glacial Maximum (LGM, ∼21–18 kya).
Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity
Authors: Galle-Treger Lauriane , Suzuki Yuzo , Patel Nisheel , Sankaranarayanan Ishwarya , Aron Jennifer L. , Maazi Hadi , Chen Lin , Akbari Omid
Published: October 2016

Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β. Additionally, the specific α7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively, our data suggest that α7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma.
Ultrasmall and phase-pure W2C nanoparticles for efficient electrocatalytic and photoelectrochemical hydrogen evolution
Authors: Gong Qiufang , Wang Yu , Hu Qi , Zhou Jigang , Feng Renfei , Duchesne Paul N. , Zhang Peng , Chen Fengjiao , Han Na , Li Yafei , Jin Chuanhong , Li Yanguang , Lee Shuit-Tong
Published: October 2016

Earlier research has been primarily focused on WC as one of the most promising earth-abundant electrocatalysts for hydrogen evolution reaction (HER), whereas the other compound in this carbide family—W2C—has received far less attention. Our theoretical calculations suggest that such a focus is misplaced and W2C is potentially more HER-active than WC. Nevertheless, the preparation of phase pure and sintering-free W2C nanostructures represents a formidable challenge. Here we develop an improved carburization method and successfully prepare ultrasmall and phase-pure W2C nanoparticles. When evaluated for HER electrocatalysis, W2C nanoparticles exhibit a small onset overpotential of 50 mV, a Tafel slope of 45 mV dec−1 and outstanding long-term cycling stability, which are dramatically improved over all existing WC-based materials. In addition, the integration of W2C nanoparticles with p-type Si nanowires enables highly active and sustainable solar-driven hydrogen production. Our results highlight the great potential of this traditionally non-popular material in HER electrocatalysis.