bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cantilever Sensors for Rapid Optical Antimicrobial Sensitivity Testing
Authors: Bennett Isabel , Pyne Alice , McKendry Rachel 
Published: June 2019

AbstractGrowing antimicrobial resistance (AMR) is a serious global threat to human health. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST) which measures bacterial growth and is therefore hampered by slow time to result (~12-24 hours). Therefore new rapid phenotypic methods for AST are urgently needed. Nanomechanical cantilever sensors have recently shown promise for rapid AST but challenges of bacterial immobilization can lead to variable results. Herein a novel cantilever-based method is described for detecting phenotypic antibiotic resistance within ~45 minutes, capable of detecting single bacteria. This method does not require complex, variable bacterial immobilization, and instead uses the laser and detector system to detect single bacterial cells in media as they pass through the laser focus. This provides a simple read out of bacterial antibiotic resistance by detecting growth (resistant) or death (sensitive), much faster than current methods. The potential of this technique demonstrated by determining resistance in both lab and clinical strains of E. coli, a key species for clinically burdensome urinary tract infections. This work provides the basis for a simple and fast diagnostic tool to detect antibiotic resistance in bacteria, reducing the health and economic burdens of AMR.
Integrative omics analysis ofPseudomonas aeruginosavirus PA5oct highlights the molecular complexity of jumbo phages
Authors: Lood Cédric , Danis-Wlodarczyk Katarzyna , Blasdel Bob G. , Jang Ho Bin , Vandenheuvel Dieter , Briers Yves , Noben Jean-Paul , van Noort Vera , Drulis-Kawa Zuzanna , Lavigne Rob 
Published: June 2019

AbstractPseudomonasvirus vB_PaeM_PA5oct is a compelling model phage to investigate phage-bacteria interactions and is a potent candidate for phage therapy. Combining hybrid genome sequencing, RNA-Seq, and mass spectrometry of virion-associated proteins allowed us to accurately assemble and annotate PA5oct’s 286,783 bp genome. It encodes 461 coding regions, of which 93 were identified as virion-associated proteins using ESI-MS/MS. RNA-seq revealed twelve tRNA genes, four ncRNA regions, and a gradual take-over of the total cell transcriptome from 21% in early infection to 93% in late infection. Although PA5oct is not organized into strictly contiguous regions of temporal transcription, defined genomic regions are expressed in early, middle, and late phases of infection. Interestingly, we observed distinct regions showing limited transcription activity throughout the infection cycle. The infection ofPseudomonas aeruginosaby PA5oct triggers the upregulation of bacterial operons related to NAD biosynthesis, Psl exopolysaccharide, and periplasmic nitrate reductase production and downregulates Type IV pili gene products, suggesting mechanisms of superinfection exclusion. We used the proteome of PA5oct to position this isolate amongst other phages using a protein-sharing network. This study expands our understanding of the molecular diversity of jumbo viruses and opens new questions towards cellular regulation and phage-encoded hijacking mechanisms.
The large GTPase, mGBP-2, regulates Rho family GTPases to inhibit migration and invadosome formation in Triple-Negative Breast Cancer cells
Authors: Nyabuto Geoffrey O. , Wilson John P. , Heilman Samantha A. , Kalb Ryan C. , Abnave Ankita V. , Vestal Deborah J. 
Published: June 2019

AbstractBreast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 40,000 women will die of breast cancer in 2019. This number of women is still too high. To lower this number, more information about the molecular players in breast cancer are needed. Several members of the Guanylate-Binding Proteins (GBPs) have been correlated with better prognosis in breast cancer. In this study, we asked if the expression of GBP-2 in breast cancer merely provided a biomarker for improved prognosis or whether it actually contributed to improving outcome. Specifically, we asked whether murine GBP-2 exhibited cell autonomous behavior that altered breast cancer cells in a manner predicted to improve prognosis. To answer this, the 4T1 model of murine Triple-Negative Breast Cancer was used. 4T1 cells themselves are highly aggressive and highly metastatic, while 67NR cells, isolated from the same tumor, do not leave the primary site. mGBP-2 did not alter cell proliferation in these two cell lines, but mGBP-2 expression inversely correlated with migration. More specifically, mGBP-2 inhibits cell migration and invadopodia formation by inhibiting the activation of Rac1, while promoting the activation of CDC42 and RhoA. Together these data demonstrate that mGBP-2 is responsible for cell autonomous activities that make breast cancer cells less aggressive.
Arp2/3 and Unc45 maintain heterochromatin stability in Drosophila polytene chromosomes
Authors: Dialynas George , Delabaere Laetitia , Chiolo Irene 
Published: June 2019

AbstractRepairing DNA double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination. InDrosophilaKc cells, accurate homologous recombination (HR) repair of heterochromatic DSBs relies on the relocalization of repair sites to the nuclear periphery before Rad51 recruitment and strand invasion. This movement is driven by Arp2/3-dependent nuclear actin filaments and myosins’ ability to walk along them. Conserved mechanisms enable the relocalization of heterochromatic DSBs in mouse cells, and their defects lead to massive ectopic recombination in heterochromatin and chromosome rearrangements. InDrosophilapolytene chromosomes, extensive DNA movement is blocked by a stiff structure of chromosome bundles. Repair pathways in this context are poorly characterized, and whether heterochromatic DSBs relocalize in these cells is unknown. Here, we show that damage in heterochromatin results in relaxation of the heterochromatic chromocenter, consistent with a dynamic response in this structure. Arp2/3, the Arp2/3 activator Scar, and the myosin activator Unc45, are required for heterochromatin stability in polytene cells, suggesting that relocalization enables heterochromatin repair in this tissue. Together, these studies reveal critical roles for actin polymerization and myosin motors in heterochromatin repair and genome stability across different organisms and tissue types.Impact StatementHeterochromatin relies on dedicated pathways for ‘safe’ recombinational repair. In mouse and fly cultured cells, DNA repair requires the movement of repair sites away from the heterochromatin ‘domain’vianuclear actin filaments and myosins. Here, we explore the importance of these pathways inDrosophilasalivary gland cells, which feature a stiff bundle of endoreduplicated polytene chromosomes. Repair pathways in polytene chromosomes are largely obscure and how nuclear dynamics operate in this context is unknown. We show that heterochromatin relaxes in response to damage, and relocalization pathways are necessary for repair and stability of heterochromatic sequences. This deepens our understanding of repair mechanisms in polytenes, revealing unexpected dynamics. It also provides a first understanding of nuclear dynamics responding to replication damage or rDNA breaks, providing a new understanding of the importance of the nucleoskeleton in genome stability. We expect these discoveries to shed light on tumorigenic processes, including therapy-induced cancer relapses.
POL30 alleles in Saccharomyces cerevisiae reveal complexities of the cell cycle and ploidy on heterochromatin assembly
Authors: Brothers Molly , Rine Jasper 
Published: June 2019

ABSTRACTIn Saccharomyces cerevisiae, transcriptional silencing at HML and HMR maintains mating-type identity. The repressive chromatin structure at these loci is replicated every cell cycle and must be re-established quickly to prevent transcription of the genes at these loci. Mutations in a component of the replisome, the Proliferating Cell Nuclear Antigen (PCNA), encoded by POL30, cause a loss of transcriptional silencing at HMR. We used an assay that captures transient losses of silencing at HML and HMR to perform extended genetic analyses of the pol30-6, pol30-8, and pol30-79 alleles. All three alleles destabilized silencing only transiently and only in cycling cells. Whereas pol30-8 caused loss of silencing by disrupting the function of Chromatin Assembly Factor 1 (CAF-I), pol30-6 and pol30-79 acted through a separate genetic pathway but one still dependent on histone chaperones. Surprisingly, the silencing-loss phenotypes depended on ploidy but not on POL30 dosage or mating-type identity. Separately from silencing loss, the pol30-6 and pol30-79 alleles also displayed high levels of mitotic recombination in diploids. These results established that histone trafficking involving PCNA at replication forks is crucial to the maintenance of chromatin state and genome stability during DNA replication. They also raised the possibility that increased ploidy may protect chromatin states when the replisome is perturbed.
Robust adaptive super twisting controller: methodology and application of a human-driven knee joint orthosis
Authors: Bkekri Rihab , Benamor Anouar , Alouane Mohamed Amine , Fried Georges , Messaoud Hassani 
Published: June 2019

Purpose
The application of the sliding mode control has two obstacle phenomena: chattering and high activity of control action. The purpose of this paper concerns a novel super-twisting adaptive sliding mode control law of a human-driven knee joint orthosis. The proposed control approach consists of using dynamically adapted control gains that ensure the establishment, in a finite time, of a real second-order sliding mode. The efficiency of the controller is evaluated using an experimental set-up.

Design/methodology/approach
This study presents the synthesis of a robust super-twisting adaptive controller for the control of a lower limb–orthosis system. The developed control strategy will take into consideration the nonlinearities as well as the uncertainties resulting from the dynamics of the lower limb–orthosis system. It must also guarantee a good follow-up of the reference trajectory.

Findings
The authors first evaluated on a valid subject, the performances of this controller which were studied and compared to several criteria. The obtained results show that the controller using the Adaptive Super-Twisting algorithm is the one that guarantees the best performance. Validation tests involved a subject and included robustness tests against external disturbances and co-contractions of antagonistic muscles.

Originality/value
The main contribution of this paper is in developing the adaptation super-twisting methodology for finding the control gain resulting in the minimization of the chattering effect.
Instances for the problem of pre-positioning emergency supplies
Authors: Turkeš Renata , Sörensen Kenneth 
Published: June 2019

PurposeDespite a growing body of research on the problem of increasing disaster preparedness by pre-positioning relief supplies at strategic locations, there is a lack of a benchmark set of problem instances that hinders thorough hypotheses testing, sensitivity analysis, model validation or solution procedure evaluation. The purpose of this paper is to address this issue by constructing a public library of diverse pre-positioning problem instances.Design/methodology/approachBy carefully manipulating some of the instance parameters, the authors generated 30 case studies that were inspired by four instances collected from the literature that focus on disasters of different type and scale that occurred in different parts of the world. In addition, the authors developed a tool to algorithmically generate arbitrarily many diverse random instances of any size.FindingsFor many purposes, the problem library can eliminate or reduce the time-consuming process of data collection, conversion, digitization, calibration and validation, while simultaneously increasing the statistical significance of research results and allowing comparison with different works in the literature.Research limitations/implicationsThe case studies are inspired by only four disasters, and some of the instance parameters are defined in a reasonable, albeit arbitrary way. The instances are also limited by the underlying problem assumptions.Practical implicationsThe instances provide a more comprehensive and balanced experimental setting (compared to a single case study) that can be used to study the pre-positioning and related problems, or derive managerial implications that can directly benefit the practitioners.Social implicationsThe instances can be used to derive practical guidelines that humanitarian workers can use on the ground to better plan their pre-positioning strategies and therefore minimize human suffering.Originality/valueThe case studies and the random instance generator are made publicly available to foster further research on the problem of pre-positioning relief supplies and humanitarian logistics in general.
Model of phosphorus diffusion in silicon for highly doped solar cell emitter layer
Authors: Filipowski Wojciech 
Published: June 2019

Purpose
The purpose of this paper was the development of a model enabling precise determination of phosphorus concentration profile in the emitter layer of a silicon solar cell on the basis of diffusion doping process duration and temperature. Fick’s second law, which is fundamental for describing the diffusion process, was assumed as the basis for the model.

Design/methodology/approach
To establish a theoretical model of the process of phosphorus diffusion in silicon, real concentration profiles measured using the secondary ion mass spectrometry (SIMS) method were used. Samples with the phosphorus dopant source applied onto monocrystalline silicon surface were placed in the heat zone of the open quartz tube furnace, where the diffusion process took place in the temperature of 880°C-940°C. The measured real concentration profiles of these samples became template profiles for the model in development.

Findings
The model was developed based on phenomena described in the literature, such as the influence of the electric field of dopant ionized atoms and the influence of dopant atom concentration nearing the maximum concentration on the value of diffusion coefficient. It was proposed to divide the diffusion area into low and high dopant concentration region.

Originality/value
A model has been established which enabled obtaining a high level of consistency between the phosphorus concentration profile developed theoretically and the real profile measured using the SIMS method. A coefficient of diffusion of phosphorus in silicon dependent on dopant concentration was calculated. Additionally, a function describing the boundary between the low and high dopant concentration regions was determined.
Resolution of Acute Priapism in Two Children With Sickle Cell Disease Who Received Nitrous Oxide
Authors: Greenwald Michael H. , Gutman Colleen K. , Morris Claudia R. 
Published: June 2019

ABSTRACTBackgroundNitrous oxide (N O) is an inhalational medication that has anxiolytic, amnestic, potent venodilatory and mild‐to‐moderate analgesic properties commonly used in the emergency department (ED) setting. N2O has a rapid onset of action (<5 minutes) and recovery (<5 minutes) and can be quickly titrated to effect without the need for IV access. It has few side effects, does not require renal or hepatic metabolism for excretion and has no reports of allergic reaction. Priapism is a serious complication of sickle cell disease (SCD) affecting approximately 35% of males, with an adverse impact on quality of life. Treatment options are limited and not evidence based, including hydration, alkalization, analgesia, oxygenation to prevent further sickling, and exchange transfusion. Patients who do not respond within 4 hours often require a painful invasive procedure that includes aspiration of blood from the corpus cavernosum and phenylephrine injections. Case reports have described a therapeutic benefit from oral pseudoephedrine, sildenafil, and intravenous (IV) arginine, however controlled clinical trials are lacking. Although a 50:50 nitrous oxide/oxygen mix is commonly used in France to enhance analgesia in patients with SCD and vasoocclusive pain events (VOE) not sufficiently responding to IV morphine, there are no reports of its use to treat priapism. We describe the effects of N2O for the treatment of acute priapism associated with SCD in a pediatric ED.MethodsThis is a case series of two adolescent boys with Hb‐SS who on 3 separate occasions presented to the ED with acute priapism that failed oral therapy (pseudoephedrine and opioids). N2O gas was utilized to help facilitate IV catheter placement.ResultsIn each presentation (at ages 8 and 10 years for patient 1; age 15 years for patient 2), the patient experienced complete resolution of the priapism within 4‐15 min of receiving N2O (max 60%). The patients were discharged from the ED following each presentation and had no recurrence during the subsequent week.ConclusionsPriapism is a challenging complication of SCD associated with long‐term morbidity and a paucity of treatment options. Opioids are commonly used. Given the risks and inconsistent results of current recommended therapy, N2O may represent a potential opioid‐sparing treatment option for priapism presenting to the ED that warrants further investigation. Although anecdotal, N2O inhalation is an intervention to consider during a time when a treating ED physician may have few alternatives.
Research‐implementation gap limits the actionability of human‐carnivore conflict studies in East Africa
Authors: Gray S. M. , Booher C. R. , Elliott K. C. , Kramer D. B. , Waller J. C. , Millspaugh J. J. , Kissui B. M. , Montgomery R. A. 
Published: June 2019

AbstractConflict with humans is one of the primary reasons why large carnivore populations are declining worldwide. Rates of human‐carnivore conflict (HCC) are particularly high in East Africa, where human settlements tend to surround protected areas, maximizing potential for human‐carnivore interactions. Despite extensive HCC research in this region, HCC persists and carnivore populations continue to decline. Evident disconnects between HCC research and conservation action, management practices and policy formation have been cited as mechanisms associated with these trends. We conducted a literature review to determine the extent to which HCC research in East Africa is actionable within the context of management and policy formation. We evaluated 36 papers for co‐production, interdisciplinary collaboration, applied or theoretical publication and stakeholder engagement. Many were published by co‐authors in academia (63.8%) and collaborative efforts between academics and non‐governmental organizations (25.0%), with limited representation outside these sectors. Collaboration with disciplines outside the natural sciences, specifically the social and political sciences (both 2.8%), was also uncommon although humans were the primary topic of study in 28% of papers. Moreover, while many papers were published in applied journals (86%), few explicitly stated policy and management objectives. Stakeholder engagement was mostly in the form of surveys and questionnaires rather than direct involvement in the research process. Our review indicates that HCC research currently lacks strong evidence of actionability and we provide recommendations for improving the practical salience of conservation research.
A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens
Authors: Huang Huey‐Jy , Curin Mirela , Banerjee Srinita , Chen Kuan‐Wei , Garmatiuk Tetiana , Resch‐Marat Yvonne , Carvalho‐Queiroz Claudia , Blatt Katharina , Gafvelin Guro , Grönlund Hans , Valent Peter , Campana Raffaela , Focke‐Tejkl Margarete , Valenta Rudolf , Vrtala Susanne 
Published: June 2019

AbstractBackgroundIn the house dust mite (HDM) Dermatophagoides pteronyssinus, Der p 1, 2, 5, 7, 21, and 23 have been identified as the most important allergens. The aim of this study was to define hypoallergenic peptides derived from the sequences of the six allergens and to use the peptides and the complete allergens to study antibody, T cell, and cytokine responses in sensitized and nonsensitized subjects.MethodsIgE reactivity of HDM‐allergic and non‐HDM‐sensitized individuals to 15 HDM allergens was established using ImmunoCAP ISAC technology. Thirty‐three peptides covering the sequences of the six HDM allergens were synthesized. Allergens and peptides were tested for IgE and IgG reactivity by ELISA and ImmunoCAP, respectively. Allergenic activity was determined by basophil activation. CD4+ T cell and cytokine responses were determined in PBMC cultures by CFSE dilution and Luminex technology, respectively.ResultsHouse dust mite allergics showed IgE reactivity only to complete allergens, whereas 31 of the 33 peptides lacked relevant IgE reactivity and allergenic activity. IgG antibodies of HDM‐allergic and nonsensitized subjects were directed against peptide epitopes and higher allergen‐specific IgG levels were found in HDM allergics. PBMC from HDM‐allergics produced higher levels of IL‐5 whereas non‐HDM‐sensitized individuals mounted higher levels of IFN‐gamma, IL‐17, pro‐inflammatory cytokines, and IL‐10.ConclusionIgG antibodies in HDM‐allergic patients recognize peptide epitopes which are different from the epitopes recognized by IgE. This may explain why naturally occurring allergen‐specific IgG antibodies do not protect against IgE‐mediated allergic inflammation. A mix of hypoallergenic peptides containing T cell epitopes of the most important HDM allergens was identified.
Visual information processing skills are associated with academic performance in Grade 2 school children
Authors: Hopkins Shelley , Black Alex A. , White Sonia L. J. , Wood Joanne M. 
Published: June 2019

AbstractPurposeThis study evaluated the association between performance on visual information processing tests and academic performance in school children.MethodsVisual‐motor integration (VMI), the Developmental Eye Movement (DEM) test, visual acuity and stereoacuity were assessed in 222 Grade 2 children (mean age: 7.90 ± 0.33 years). Academic performance was assessed using standardized tests of reading and mathematics (PAT‐R and PAT‐M). Linear regression analyses examined associations between visual information processing (VMI and DEM) and academic measures, adjusting for school socio‐economic background and age. Receiver operating characteristic (ROC) analysis was used to assess the ability of the tests to identify children with below average academic performance.ResultsVisual‐motor integration (VMI) and DEM (horizontal time) were most strongly associated with PAT‐R and PAT‐M. Linear regression models explained 28.6% of variance in PAT‐R (VMI: standardized regression coefficient = 0.31, p < 0.01; DEM horizontal time: −0.28, p < 0.01) and 24.1% of variance in PAT‐M (VMI: standardized regression coefficient = 0.29, p < 0.01; DEM horizontal time: −0.16, p = 0.02). Receiver operating characteristic (ROC) curve analysis indicated that VMI was most strongly associated with below average PAT‐R (area under curve [AUC] of 0.74 [95% CI: 0.67–0.81]) and PAT‐M (AUC of 0.73 [95% CI: 0.66–0.81]).ConclusionVisual‐motor integration (VMI) was most strongly associated with reading and mathematics scores in school children. A child's academic performance can be an important factor in their optometric management. The ability of clinical tests to identify children at risk of underachieving academically provides additional support to clinicians in managing their patients.