bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Whole-Genome Sequence of
Sphingobium
sp. 22B, a Polycyclic Aromatic Hydrocarbon–Degrading Bacterium from Semiarid Patagonia, Argentina
Authors: Madueño L. , Macchi M. , Morelli I. S. , Coppotelli B. M. 
Published: June 2016

ABSTRACT

Sphingobium
sp. 22B is a polycyclic aromatic hydrocarbon–degrading strain isolated from Patagonia, Argentina, with capabilities to withstand the environmental factors of that semiarid region. The draft genome shows the presence of genes related with responses to carbon starvation and drying environmental conditions.
Curcumin Reduces the Motility of Salmonella enterica Serovar Typhimurium by Binding to the Flagella, Thereby Leading to Flagellar Fragility and Shedding
Authors: Marathe Sandhya Amol , Balakrishnan Arjun , Negi Vidya Devi , Sakorey Deepika , Chandra Nagasuma , Chakravortty Dipshikha 
Published: June 2016

ABSTRACT

One of the important virulence properties of the pathogen is its ability to travel to a favorable environment, cross the viscous mucus barrier (intestinal barrier for enteric pathogens), and reach the epithelia to initiate pathogenesis with the help of an appendage, like flagella. Nonetheless, flagella can act as an “Achilles heel,” revealing the pathogen's presence to the host through the stimulation of innate and adaptive immune responses. We assessed whether curcumin, a dietary polyphenol, could alter the motility of
Salmonella
, a foodborne pathogen. It reduced the motility of
Salmonella enterica
serovar Typhimurium by shortening the length of the flagellar filament (from ∼8 μm to ∼5 μm) and decreasing its density (4 or 5 flagella/bacterium instead of 8 or 9 flagella/bacterium). Upon curcumin treatment, the percentage of flagellated bacteria declined from ∼84% to 59%. However, no change was detected in the expression of the flagellin gene and protein. A fluorescence binding assay demonstrated binding of curcumin to the flagellar filament. This might make the filament fragile, breaking it into smaller fragments. Computational analysis predicted the binding of curcumin, its analogues, and its degraded products to a flagellin molecule at an interface between domains D1 and D2. Site-directed mutagenesis and a fluorescence binding assay confirmed the binding of curcumin to flagellin at residues ASN120, ASP123, ASN163, SER164, ASN173, and GLN175.

IMPORTANCE
This work, to our knowledge the first report of its kind, examines how curcumin targets flagellar density and affects the pathogenesis of bacteria. We found that curcumin does not affect any of the flagellar synthesis genes. Instead, it binds to the flagellum and makes it fragile. It increases the torsional stress on the flagellar filament that then breaks, leaving fewer flagella around the bacteria. Flagella, which are crucial ligands for Toll-like receptor 5, are some of the most important appendages of
Salmonella
. Curcumin is an important component of turmeric, which is a major spice used in Asian cooking. The loss of flagella can, in turn, change the pathogenesis of bacteria, making them more robust and fit in the host.
Myeloid Cells in Cutaneous Wound Repair
Authors: Cash Jenna L. , Martin Paul 
Published: June 2016

ABSTRACTCutaneous wound repair is a complex, dynamic process with the goal of rapidly sealing any breach in the skin’s protective barrier. Myeloid cells compose a significant proportion of the inflammatory cells recruited to a wound site and play important roles in decontaminating the injured tissue of any invading microorganisms. Subsequently, myeloid cells are able to influence many aspects of the healing response, in part through their capacity to release a large array of signaling molecules that allow them to communicate with and regulate the behavior of other wound cells and in turn, be themselves exquisitely regulated by the wound microenvironment. Macrophages, for example, appear to play important, temporally changing roles in the initiation of scarring and subsequently in matrix remodeling to resolve fibrosis. In this way, myeloid cells seem to play both positive (e.g., pathogen killing and matrix remodeling) and negative (e.g., scarring) roles in wound repair. Further research is of course needed to elucidate the precise temporal and spatial myeloid cell phenotypes and behaviors and ultimately to design effective strategies to optimize the beneficial functions of these cells while minimizing their detrimental contributions to improve wound healing in the clinic.
Clinical excellence: evidence on the assessment of senior doctors' applications to the UK Advisory Committee on Clinical Excellence Awards. Analysis of complete national data set
Authors: Campbell John L , Abel Gary 
Published: June 2016

ObjectivesTo inform the rational deployment of assessor resource in the evaluation of applications to the UK Advisory Committee on Clinical Excellence Awards (ACCEA).SettingACCEA are responsible for a scheme to financially reward senior doctors in England and Wales who are assessed to be working over and above the standard expected of their role.ParticipantsAnonymised applications of consultants and senior academic GPs for awards were considered by members of 14 regional subcommittees and 2 national assessing committees during the 2014–2015 round of applications.DesignIt involved secondary analysis of complete anonymised national data set.Primary and secondary outcome measuresWe analysed scores for each of 1916 applications for a clinical excellence award across 4 levels of award. Scores were provided by members of 16 subcommittees. We assessed the reliability of assessments and described the variance in the assessment of scores.ResultsMembers of regional subcommittees assessed 1529 new applications and 387 renewal applications. Average scores increased with the level of application being made. On average, applications were assessed by 9.5 assessors. The highest contributions to the variance in individual assessors' assessments of applications were attributable to assessors or to residual variance. The applicant accounted for around a quarter of the variance in scores for new bronze applications, with this proportion decreasing for higher award levels. Reliability in excess of 0.7 can be attained where 4 assessors score bronze applications, with twice as many assessors being required for higher levels of application.ConclusionsAssessment processes pertaining in the competitive allocation of public funds need to be credible and efficient. The present arrangements for assessing and scoring applications are defensible, depending on the level of reliability judged to be required in the assessment process. Some relatively minor reconfiguration in approaches to scoring might usefully be considered in future rounds of assessment.
More about neutron Majorana mass from exotic instantons: An alternative mechanism in low-scale string theory
Authors: Addazi Andrea 
Published: June 2016

We discuss an alternative for baryon-violating six quarks transition in the context of low scale string theory. In particular, with M[Formula: see text] = 10–103 TeV, such a transition can be mediated by two color-triplets through a quartic coupling with down-quarks, generated by exotic instantons, in a calculable and controllable way. We show how flavor-changing neutral currents (FCNCs) limits on color-triplet mass are well compatible with [Formula: see text] oscillation ones. If an [Formula: see text] transition was found, this would be an indirect hint for our model. This would strongly motivate searches for direct channels in proton–proton colliders. In fact, our model can be directly tested in an experimentally challenging 100–1000 TeV proton–proton collider, searching for our desired color-triplet states and an evidence for exotic instantons resonances, in addition to stringy Regge resonances, anomalous Z[Formula: see text]-bosons and gauged megaxion. In particular, our scenario can be related to the 750 GeV diphoton hint identifying it with the gauged megaxion dual to the B-field. On the other hand, this scenario is compatible with TeV-ish color triplets visible at large hadron collider (LHC) and with 1–10 TeV string scale, i.e. stringy resonances at LHC.
Ethiopian volcanic hazards: a changing research landscape
Authors: Vye-Brown C. , Sparks R. S. J. , Lewi E. , Mewa G. , Asrat A. , Loughlin S. C. , Mee K. , Wright T. J. 
Published: June 2016

Abstract
Collaborative research projects have a significant role in filling the knowledge gaps that are obstacles to the rigorous assessment of volcanic hazards in some locations. Research is essential to generate the evidence on which raising awareness of volcanic hazards, monitoring and early warning systems, risk reduction activities and efforts to increase resilience can be built. We report the current state of volcanic hazards research and practice in Ethiopia and on the collaborative process used in the Afar Rift Consortium project to promote awareness of volcanic hazards. Effective dissemination of findings to stakeholders and the integration of results into existing practice need leadership by in-country researchers, effective long-term collaboration with other researchers (e.g. international groups) and operational scientists, in addition to integration with existing programmes related to disaster risk reduction initiatives.
Data partitioning for single-round multi-join evaluation in massively parallel systems
Authors: Ameloot Tom J. , Geck Gaetano , Ketsman Bas , Neven Frank , Schwentick Thomas 
Published: June 2016

A dominant cost for query evaluation in modern massively distributed systems is the number of communication rounds. For this reason, there is a growing interest in single-round multiway join algorithms where data is first reshuffled over many servers and then evaluated in a parallel but communication- free way. The reshuffling itself is specified as a distribution policy. We introduce a correctness condition, called parallel-correctness, for the evaluation of queries w.r.t. a distribution policy. We provide a semantical characterization for when conjunctive queries (and extensions thereof) are parallel-correct and give matching complexity bounds for the associated decision problem.
Motivated by scenarios for workload optimization, we further consider the problem of parallel-correctness transfer from a query Q to a query Q0, that is, whether Q0 is parallelcorrect for all distribution policies for which Q is parallelcorrect. In this case, Q0 can always be evaluated after Q without repartitioning the data. We provide a semantical characterization for parallel-correctness transfer and provide matching complexity bounds for the associated decision problem for conjunctive queries (and extensions). Finally, we investigate restrictions of queries and families of distribution policies with better complexities, including, for instance, the Hypercube distributions.
Resource Bricolage for Parallel DBMSs on Heterogeneous Clusters
Authors: Li Jiexing , Naughton Jeffrey , Nehme Rimma V. 
Published: June 2016

Running parallel database systems in an environment with heterogeneous resources has become increasingly common, due to cluster evolution and increasing interest in moving applications into public clouds or shared infrastructures. For database systems running in a heterogeneous cluster, the default uniform data partitioning strategy may overload some of the slow machines while at the same time it may underutilize the more powerful machines. Since the processing time of a parallel query is determined by the slowest machine, such an allocation strategy may result in a significant query performance degradation.
We take a first step to address this problem by introducing a technique we call resource bricolage that improves database performance in heterogeneous environments. Our approach quantifies the performance differences among machines with various resources as they process workloads with diverse resource requirements. We formalize the problem of minimizing workload execution time and view it as an optimization problem, and then we employ linear programming to obtain a recommended data partitioning scheme. We verify the effectiveness of our technique with an extensive experimental study on a commercial database system.
Proteasome Addiction Defined in Ewing Sarcoma Is Effectively Targeted by a Novel Class of 19S Proteasome Inhibitors
Authors: Shukla Neerav , Somwar Romel , Smith Roger S. , Ambati Sri , Munoz Stanley , Merchant Melinda , D'Arcy Padraig , Wang Xin , Kobos Rachel , Antczak Christophe , Bhinder Bhavneet , Shum David , Radu Constantin , Yang Guangbin , Taylor Barry S. , Ng Charlotte K.Y. , Weigelt Britta , Khodos Inna , de Stanchina Elisa , Reis-Filho Jorge S. , Ouerfelli Ouathek , Linder Stig , Djaballah Hakim , Ladanyi Marc 
Published: June 2016

Abstract
Ewing sarcoma is a primitive round cell sarcoma with a peak incidence in adolescence that is driven by a chimeric oncogene created from the fusion of the EWSR1 gene with a member of the ETS family of genes. Patients with metastatic and recurrent disease have dismal outcomes and need better therapeutic options. We screened a library of 309,989 chemical compounds for growth inhibition of Ewing sarcoma cells to provide the basis for the development of novel therapies and to discover vulnerable pathways that might broaden our understanding of the pathobiology of this aggressive sarcoma. This screening campaign identified a class of benzyl-4-piperidone compounds that selectively inhibit the growth of Ewing sarcoma cell lines by inducing apoptosis. These agents disrupt 19S proteasome function through inhibition of the deubiquitinating enzymes USP14 and UCHL5. Functional genomic data from a genome-wide shRNA screen in Ewing sarcoma cells also identified the proteasome as a node of vulnerability in Ewing sarcoma cells, providing orthologous confirmation of the chemical screen findings. Furthermore, shRNA-mediated silencing of USP14 or UCHL5 in Ewing sarcoma cells produced significant growth inhibition. Finally, treatment of a xenograft mouse model of Ewing sarcoma with VLX1570, a benzyl-4-piperidone compound derivative currently in clinical trials for relapsed multiple myeloma, significantly inhibited in vivo tumor growth. Overall, our results offer a preclinical proof of concept for the use of 19S proteasome inhibitors as a novel therapeutic strategy for Ewing sarcoma. Cancer Res; 76(15); 4525–34. ©2016 AACR.
Long-term Particulate Matter Exposures during Adulthood and Risk of Breast Cancer Incidence in the Nurses' Health Study II Prospective Cohort
Authors: Hart Jaime E. , Bertrand Kimberly A. , DuPre Natalie , James Peter , Vieira Verónica M. , Tamimi Rulla M. , Laden Francine 
Published: June 2016

Abstract
Background: There is increasing concern that environmental exposures, such as air pollution, may be related to increasing rates of breast cancer; however, results from cohort studies have been mixed. We examined the association between particulate matter (PM) and measures of distance to roadway with the risk of incident breast cancer in the prospective nationwide Nurses' Health Study II (NHSII) cohort.
Methods: Incident invasive breast cancer from 1993 to 2011 (N = 3,416) was assessed among 115,921 women in the NHSII cohort. Time-varying Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (95% CI) for increases in ambient exposures to PM10, PM2.5–10, and PM2.5 and residential roadway proximity categories.
Results: In multivariable adjusted models, there was little evidence of an increased risk of breast cancer (or any of the receptor-specific subtypes) overall or by menopausal status with PM exposure. There was, however, a suggestion of increased risks among women living &lt;50 m of the largest road type (HR = 1.60; 95% CI, 0.80–3.21) or within &lt;50 m of the two largest road types (1.14; 95% CI, 0.84–1.54) compared with women living farther (≥200 m) away.
Conclusions: Among women in the NHSII, we found no statistically significant associations between particulate matter exposures and incidence of breast cancer overall, by menopausal status, or by hormone receptor subtype. There was, however, a suggestion that residential proximity to major roadways may be associated with increased risk.
Impact: These results suggest no elevated breast cancer risk with increasing exposures to particulate matter air pollution, but that other traffic-related exposures may be important. Cancer Epidemiol Biomarkers Prev; 25(8); 1274–6. ©2016 AACR.
High Levels of Expression of P-glycoprotein/Multidrug Resistance Protein Result in Resistance to Vintafolide
Authors: Guertin Amy D. , O'Neil Jennifer , Stoeck Alexander , Reddy Joseph A. , Cristescu Razvan , Haines Brian B. , Hinton Marlene C. , Dorton Ryan , Bloomfield Alicia , Nelson Melissa , Vetzel Marilynn , Lejnine Serguei , Nebozhyn Michael , Zhang Theresa , Loboda Andrey , Picard Kristen L. , Schmidt Emmett V. , Dussault Isabelle , Leamon Christopher P. 
Published: June 2016

Abstract
Targeting surface receptors overexpressed on cancer cells is one way to specifically treat cancer versus normal cells. Vintafolide (EC145), which consists of folate linked to a cytotoxic small molecule, desacetylvinblastine hydrazide (DAVLBH), takes advantage of the overexpression of folate receptor (FR) on cancer cells. Once bound to FR, vintafolide enters the cell by endocytosis, and the reducing environment of the endosome cleaves the linker, releasing DAVLBH to destabilize microtubules. Vintafolide has shown efficacy and improved tolerability compared with DAVLBH in FR-positive preclinical models. As the first FR-targeting drug to reach the clinic, vintafolide has achieved favorable responses in phase II clinical trials in FR-positive ovarian and lung cancer. However, some FR-positive patients in these clinical trials do not respond to vintafolide. We sought to identify potential biomarkers of resistance to aid in the future development of this and other FR-targeting drugs. Here, we confirm that high P-glycoprotein (P-gp) expression was the strongest predictor of resistance to DAVLBH in a panel of 359 cancer cell lines. Furthermore, targeted delivery of DAVLBH via the FR, as in vintafolide, fails to overcome P-gp–mediated efflux of DAVLBH in both in vitro and in vivo preclinical models. Therefore, we suggest that patients whose tumors express high levels of P-gp be excluded from future clinical trials for vintafolide as well as other FR-targeted therapeutics bearing a P-gp substrate. Mol Cancer Ther; 15(8); 1998–2008. ©2016 AACR.
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression
Authors: Black Jonathan , Menderes Gulden , Bellone Stefania , Schwab Carlton L. , Bonazzoli Elena , Ferrari Francesca , Predolini Federica , De Haydu Christopher , Cocco Emiliano , Buza Natalia , Hui Pei , Wong Serena , Lopez Salvatore , Ratner Elena , Silasi Dan-Arin , Azodi Masoud , Litkouhi Babak , Schwartz Peter E. , Goedings Peter , Beusker Patrick H. , van der Lee Miranda M.C. , Timmers C. Marco , Dokter Wim H.A. , Santin Alessandro D. 
Published: June 2016

Abstract
Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer. Up to 35% of USC may overexpress the HER2/neu oncogene at strong (i.e., 3+) levels by IHC while an additional 40% to 50% express HER2/neu at moderate (2+) or low (1+) levels. We investigated the efficacy of SYD985, (Synthon Biopharmaceuticals), a novel HER2-targeting antibody–drug conjugate (ADC) composed of the mAb trastuzumab linked to a highly potent DNA-alkylating agent (i.e., duocarmycin) in USC. We also compared the antitumor activity of SYD985 in head-to-head experiments to trastuzumab emtansine (T-DM1), a FDA-approved ADC, against multiple primary USC cell lines expressing different levels of HER2/neu in in vitro and in vivo experiments. Using antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability, and bystander killing assays as well as propidium iodide–based flow cytometry assays and multiple in vivo USC mouse xenograft models, we demonstrate for the first time that SYD985 is a novel ADC with activity against USC with strong (3+) as well as low to moderate (i.e., 1+/2+) HER2/neu expression. SYD985 is 10- to 70-fold more potent than T-DM1 in comparative experiments and, unlike T-DM1, it is active against USC demonstrating moderate/low or heterogeneous HER2/neu expression. Clinical studies with SYD985 in patients harboring chemotherapy-resistant USC with low, moderate, and high HER2 expression are warranted. Mol Cancer Ther; 15(8); 1900–9. ©2016 AACR.
So You Can Teach Old Fibroblasts New Tricks
Authors: Virós Amaya , Girotti Maria Romina , Marais Richard 
Published: June 2016

Abstract
Summary: New data show that as dermal fibroblasts grow old, they increase their secretion of the WNT antagonist sFRP2 to drive melanoma cell metastasis. sFRP2 suppresses β-catenin and MITF signaling in melanoma cells, downregulating the redox regulator APE1, making melanoma cells more sensitive to oxidative stress and driving resistance to BRAF inhibitors. Thus, the aging microenvironment in elderly patient skin activates a signaling pathway that drives more aggressive melanoma cell behavior. Cancer Discov; 6(6); 581–3. ©2016 AACR.
Clinical Outcomes of Transplanted Modified Bone Marrow–Derived Mesenchymal Stem Cells in Stroke
Authors: Steinberg Gary K. , Kondziolka Douglas , Wechsler Lawrence R. , Lunsford L. Dade , Coburn Maria L. , Billigen Julia B. , Kim Anthony S. , Johnson Jeremiah N. , Bates Damien , King Bill , Case Casey , McGrogan Michael , Yankee Ernest W. , Schwartz Neil E. 
Published: June 2016

Background and Purpose—
Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes.

Methods—
Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow–derived mesenchymal stem cells (SB623).

Results—

All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5–10.3;
P
<0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, −2.7 to −1.3;
P
<0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4–27.0;
P
<0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6–18.2;
P
<0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (
P
<0.001 for European Stroke Scale).

Conclusions—
In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01287936.