cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1569258
title: Bootstrap hypothesis testing in generalized additive models for comparing curves of treatments in longitudinal studies

description: The study of the effect of a treatment may involve the evaluation of a variable at a number of moments. When assuming a smooth curve for the mean response along time, estimation can be afforded by spline regression, in the context of generalized additive models. The novelty of our work lies in the construction of hypothesis tests to compare two curves of treatments in any interval of time for several types of response variables. The within-subject correlation is not modeled but is considered to obtain valid inferences by the use of bootstrap. We propose both semiparametric and nonparametric bootstrap approaches, based on resampling vectors of residuals or responses, respectively. Simulation studies revealed a good performance of the tests, considering, for the outcome, different distribution functions in the exponential family and varying the correlation between observations along time. We show that the sizes of bootstrap tests are close to the nominal value, with tests based on a standardized statistic having slightly better size properties. The power increases as the distance between curves increases and decreases when correlation gets higher. The usefulness of these statistical tools was confirmed using real data, thus allowing to detect changes in fish behavior when exposed to the toxin microcystin-RR.
DOI: 10.6084/m9.figshare.1569258.v1
title: Bootstrap hypothesis testing in generalized additive models for comparing curves of treatments in longitudinal studies

description: The study of the effect of a treatment may involve the evaluation of a variable at a number of moments. When assuming a smooth curve for the mean response along time, estimation can be afforded by spline regression, in the context of generalized additive models. The novelty of our work lies in the construction of hypothesis tests to compare two curves of treatments in any interval of time for several types of response variables. The within-subject correlation is not modeled but is considered to obtain valid inferences by the use of bootstrap. We propose both semiparametric and nonparametric bootstrap approaches, based on resampling vectors of residuals or responses, respectively. Simulation studies revealed a good performance of the tests, considering, for the outcome, different distribution functions in the exponential family and varying the correlation between observations along time. We show that the sizes of bootstrap tests are close to the nominal value, with tests based on a standardized statistic having slightly better size properties. The power increases as the distance between curves increases and decreases when correlation gets higher. The usefulness of these statistical tools was confirmed using real data, thus allowing to detect changes in fish behavior when exposed to the toxin microcystin-RR.
DOI: 10.6084/m9.figshare.1569247
title: Contact-Lens-Associated Purpureocillium Keratitis: Risk Factors, Microbiologic Characteristics, Clinical Course, and Outcomes

description: <i>Purpose</i>: To study the risk factors, microbiologic characteristics, clinical course, and outcomes of patients with Purpureocillium keratitis at a tertiary eye care center in south Florida. <i>Materials and Methods</i>: All medical records during a seven-year period starting January 1, 2007, were reviewed. Twenty-eight culture-proven Purpureocillium keratitis cases with complete medical records presenting to our institution were included in this retrospective, observational case series. Data collected included predisposing factors, therapeutic interventions, treatment duration, and visual outcomes. <i>Results</i>: Twenty patients (71.4%) had a history of soft contact lens use, with only two for therapeutic use. Other identified risk factors were trauma and immunosuppression. Fifteen patients (53.6%) received topical corticosteroid treatment prior to the diagnosis of fungal keratitis. Thirteen patients (46.4%) were on Natamycin treatment prior to Purpureocillium identification. As a group, the average best-corrected visual acuity (BCVA) at presentation was 1.1 logMAR; upon the final evaluation, it was 1.0 logMAR. The BCVA on last evaluation for the eight patients presenting to our institution within two weeks of onset of symptoms was 0.3 log MAR, and all patients in this group responded to medical management. The final BCVA for 20 patients presenting two weeks after onset of symptoms was 1.2 logMAR. There was a significant difference in the final BCVA between Group 1 and Group 2 (<i>p</i> = 0.004), but no difference in steroid use or previous treatments. Previous steroid use tended to extend time to presentation and was significantly associated with a worse final visual outcome (1.2 versus 0.6 logMAR; <i>p</i> = 0.0474). Previous Natamycin use was significantly associated with a worse final visual outcome (1.4 versus 0.6 logMAR; <i>p</i> = 0.014). <i>Conclusion</i>: Purpureocillium keratitis can have devastating consequences to visual function and even lead to enucleation. Physicians should make every effort to arrive at an earlier microbiological diagnosis, as this is associated with better outcomes and less need for surgical intervention. The first line use of voriconazole is recommended, and steroid use should be avoided, as their previous use is associated with worse visual outcomes.
DOI: 10.6084/m9.figshare.1569247.v2
title: Contact-Lens-Associated Purpureocillium Keratitis: Risk Factors, Microbiologic Characteristics, Clinical Course, and Outcomes

description: <i>Purpose</i>: To study the risk factors, microbiologic characteristics, clinical course, and outcomes of patients with Purpureocillium keratitis at a tertiary eye care center in south Florida. <i>Materials and Methods</i>: All medical records during a seven-year period starting January 1, 2007, were reviewed. Twenty-eight culture-proven Purpureocillium keratitis cases with complete medical records presenting to our institution were included in this retrospective, observational case series. Data collected included predisposing factors, therapeutic interventions, treatment duration, and visual outcomes. <i>Results</i>: Twenty patients (71.4%) had a history of soft contact lens use, with only two for therapeutic use. Other identified risk factors were trauma and immunosuppression. Fifteen patients (53.6%) received topical corticosteroid treatment prior to the diagnosis of fungal keratitis. Thirteen patients (46.4%) were on Natamycin treatment prior to Purpureocillium identification. As a group, the average best-corrected visual acuity (BCVA) at presentation was 1.1 logMAR; upon the final evaluation, it was 1.0 logMAR. The BCVA on last evaluation for the eight patients presenting to our institution within two weeks of onset of symptoms was 0.3 log MAR, and all patients in this group responded to medical management. The final BCVA for 20 patients presenting two weeks after onset of symptoms was 1.2 logMAR. There was a significant difference in the final BCVA between Group 1 and Group 2 (<i>p</i> = 0.004), but no difference in steroid use or previous treatments. Previous steroid use tended to extend time to presentation and was significantly associated with a worse final visual outcome (1.2 versus 0.6 logMAR; <i>p</i> = 0.0474). Previous Natamycin use was significantly associated with a worse final visual outcome (1.4 versus 0.6 logMAR; <i>p</i> = 0.014). <i>Conclusion</i>: Purpureocillium keratitis can have devastating consequences to visual function and even lead to enucleation. Physicians should make every effort to arrive at an earlier microbiological diagnosis, as this is associated with better outcomes and less need for surgical intervention. The first line use of voriconazole is recommended, and steroid use should be avoided, as their previous use is associated with worse visual outcomes.
DOI: 10.6084/m9.figshare.1569247.v1
title: Contact-Lens-Associated Purpureocillium Keratitis: Risk Factors, Microbiologic Characteristics, Clinical Course, and Outcomes

description: ABSTRACT<i>Purpose</i>: To study the risk factors, microbiologic characteristics, clinical course, and outcomes of patients with Purpureocillium keratitis at a tertiary eye care center in south Florida. <i>Materials and Methods</i>: All medical records during a seven-year period starting January 1, 2007, were reviewed. Twenty-eight culture-proven Purpureocillium keratitis cases with complete medical records presenting to our institution were included in this retrospective, observational case series. Data collected included predisposing factors, therapeutic interventions, treatment duration, and visual outcomes. <i>Results</i>: Twenty patients (71.4%) had a history of soft contact lens use, with only two for therapeutic use. Other identified risk factors were trauma and immunosuppression. Fifteen patients (53.6%) received topical corticosteroid treatment prior to the diagnosis of fungal keratitis. Thirteen patients (46.4%) were on Natamycin treatment prior to Purpureocillium identification. As a group, the average best-corrected visual acuity (BCVA) at presentation was 1.1 logMAR; upon the final evaluation, it was 1.0 logMAR. The BCVA on last evaluation for the eight patients presenting to our institution within two weeks of onset of symptoms was 0.3 log MAR, and all patients in this group responded to medical management. The final BCVA for 20 patients presenting two weeks after onset of symptoms was 1.2 logMAR. There was a significant difference in the final BCVA between Group 1 and Group 2 (<i>p</i> = 0.004), but no difference in steroid use or previous treatments. Previous steroid use tended to extend time to presentation and was significantly associated with a worse final visual outcome (1.2 versus 0.6 logMAR; <i>p</i> = 0.0474). Previous Natamycin use was significantly associated with a worse final visual outcome (1.4 versus 0.6 logMAR; <i>p</i> = 0.014). <i>Conclusion</i>: Purpureocillium keratitis can have devastating consequences to visual function and even lead to enucleation. Physicians should make every effort to arrive at an earlier microbiological diagnosis, as this is associated with better outcomes and less need for surgical intervention. The first line use of voriconazole is recommended, and steroid use should be avoided, as their previous use is associated with worse visual outcomes.
DOI: 10.6084/m9.figshare.1569225
title: Optimized Culture System to Induce Neurite Outgrowth From Retinal Ganglion Cells in Three-Dimensional Retinal Aggregates Differentiated From Mouse and Human Embryonic Stem Cells

description: <i>Purpose</i>: To establish a practical research tool for studying the pathogenesis of retinal ganglion cell (RGC) diseases, we optimized culture procedures to induce neurite outgrowth from three-dimensional self-organizing optic vesicles (3D-retinas) differentiated <i>in vitro</i> from mouse and human embryonic stem cells (ESCs). <i>Materials and methods</i>: The developing 3D-retinas isolated at various time points were placed on Matrigel-coated plates and cultured in media on the basis of the 3D-retinal culture or the retinal organotypic culture protocol. The number, length, and morphology of the neurites in each culture condition were compared. <i>Results</i>: First, we confirmed that Venus-positive cells were double-labeled with a RGC marker, Brn3a, in the 3D-retina differentiated from Fstl4::Venus mouse ESCs, indicating specific RGC-subtype differentiation. Second, Venus-positive neurites grown from these RGC subsets were positive for beta-III tubulin and SMI312 by immunohistochemistry. Enhanced neurite outgrowth was observed in the B27-supplemented Neurobasal-A medium on Matrigel-coated plates from the optic vesicles isolated after 14 days of differentiation from mouse ESCs. For the differentiated RGCs from human ESCs, we obtained neurite extension of &gt;4 mm by modifying Matrigel coating and the culture medium from the mouse RGC culture. <i>Conclusion</i>: We successfully optimized the culture conditions to enhance lengthy and high-frequency neurite outgrowth in mouse and human models. The procedure would be useful for not only developmental studies of RGCs, including maintenance and projection, but also clinical, pathological, and pharmacological studies of human RGC diseases.
DOI: 10.6084/m9.figshare.1569221
title: Premature termination of <i>GAT1</i> transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production

description: The first step in executing the genetic program of a cell is production of mRNA. In yeast, almost every gene is transcribed as multiple distinct isoforms, differing at their 5′ and/or 3′ termini. However, the implications and functional significance of the transcriptome-wide diversity of mRNA termini remains largely unexplored. In this paper, we show that the <i>GAT1</i> gene, encoding a transcriptional activator of nitrogen-responsive catabolic genes, produces a variety of mRNAs differing in their 5′ and 3′ termini. Alternative transcription initiation leads to the constitutive, low level production of 2 full length proteins differing in their N-termini, whereas premature transcriptional termination generates a short, highly nitrogen catabolite repression- (NCR-) sensitive transcript that, as far as we can determine, is not translated under the growth conditions we used, but rather likely protects the cell from excess Gat1.
DOI: 10.6084/m9.figshare.1569224
title: Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances

description: Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released <i>N</i>-acetyl-β-glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y<sub>12</sub> antagonist cangrelor, while inhibition of thromboxane A<sub>2</sub> formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug <i>S</i>-nitroso-<i>N</i>-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I<sub>2</sub> (PGI<sub>2</sub>) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI<sub>2</sub> or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y<sub>12</sub> receptors is important for efficient platelet lysosomal exocytosis by thrombin.
DOI: 10.6084/m9.figshare.1569225.v1
title: Optimized Culture System to Induce Neurite Outgrowth From Retinal Ganglion Cells in Three-Dimensional Retinal Aggregates Differentiated From Mouse and Human Embryonic Stem Cells

description: <i>Purpose</i>: To establish a practical research tool for studying the pathogenesis of retinal ganglion cell (RGC) diseases, we optimized culture procedures to induce neurite outgrowth from three-dimensional self-organizing optic vesicles (3D-retinas) differentiated <i>in vitro</i> from mouse and human embryonic stem cells (ESCs). <i>Materials and methods</i>: The developing 3D-retinas isolated at various time points were placed on Matrigel-coated plates and cultured in media on the basis of the 3D-retinal culture or the retinal organotypic culture protocol. The number, length, and morphology of the neurites in each culture condition were compared. <i>Results</i>: First, we confirmed that Venus-positive cells were double-labeled with a RGC marker, Brn3a, in the 3D-retina differentiated from Fstl4::Venus mouse ESCs, indicating specific RGC-subtype differentiation. Second, Venus-positive neurites grown from these RGC subsets were positive for beta-III tubulin and SMI312 by immunohistochemistry. Enhanced neurite outgrowth was observed in the B27-supplemented Neurobasal-A medium on Matrigel-coated plates from the optic vesicles isolated after 14 days of differentiation from mouse ESCs. For the differentiated RGCs from human ESCs, we obtained neurite extension of &gt;4 mm by modifying Matrigel coating and the culture medium from the mouse RGC culture. <i>Conclusion</i>: We successfully optimized the culture conditions to enhance lengthy and high-frequency neurite outgrowth in mouse and human models. The procedure would be useful for not only developmental studies of RGCs, including maintenance and projection, but also clinical, pathological, and pharmacological studies of human RGC diseases.
DOI: 10.6084/m9.figshare.1569224.v1
title: Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances

description: Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released <i>N</i>-acetyl-β-glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y<sub>12</sub> antagonist cangrelor, while inhibition of thromboxane A<sub>2</sub> formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug <i>S</i>-nitroso-<i>N</i>-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I<sub>2</sub> (PGI<sub>2</sub>) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI<sub>2</sub> or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y<sub>12</sub> receptors is important for efficient platelet lysosomal exocytosis by thrombin.
DOI: 10.6084/m9.figshare.1569218
title: Data for the article "The effect of gaze position on reaching movements in an obstacle avoidance task"

description: The aim of the current study was to investigate whether movement path selection varies with gaze position. To this end, we employed an obstacle avoidance paradigm in two separate experiments. The 'Experiment1data' and 'Experiment2data' files below contain the movement data from both experiments. While the 'Experiment2_MeanLateralGaze&IndexPos' file contains the mean gaze and movement data for the second experiment. The 'README' file contains a detailed description of what is contained within the data files.
DOI: 10.6084/m9.figshare.1569221.v1
title: Premature termination of <i>GAT1</i> transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production

description: The first step in executing the genetic program of a cell is production of mRNA. In yeast, almost every gene is transcribed as multiple distinct isoforms, differing at their 5′ and/or 3′ termini. However, the implications and functional significance of the transcriptome-wide diversity of mRNA termini remains largely unexplored. In this paper, we show that the <i>GAT1</i> gene, encoding a transcriptional activator of nitrogen-responsive catabolic genes, produces a variety of mRNAs differing in their 5′ and 3′ termini. Alternative transcription initiation leads to the constitutive, low level production of 2 full length proteins differing in their N-termini, whereas premature transcriptional termination generates a short, highly nitrogen catabolite repression- (NCR-) sensitive transcript that, as far as we can determine, is not translated under the growth conditions we used, but rather likely protects the cell from excess Gat1.
DOI: 10.6084/m9.figshare.1569221.v2
title: Premature termination of <i>GAT1</i> transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production

description: The first step in executing the genetic program of a cell is production of mRNA. In yeast, almost every gene is transcribed as multiple distinct isoforms, differing at their 5′ and/or 3′ termini. However, the implications and functional significance of the transcriptome-wide diversity of mRNA termini remains largely unexplored. In this paper, we show that the <i>GAT1</i> gene, encoding a transcriptional activator of nitrogen-responsive catabolic genes, produces a variety of mRNAs differing in their 5′ and 3′ termini. Alternative transcription initiation leads to the constitutive, low level production of 2 full length proteins differing in their N-termini, whereas premature transcriptional termination generates a short, highly nitrogen catabolite repression- (NCR-) sensitive transcript that, as far as we can determine, is not translated under the growth conditions we used, but rather likely protects the cell from excess Gat1.
DOI: 10.6084/m9.figshare.1569204
title: Development of formulae for estimating amylose content and resistant starch content based on the pasting properties measured by RVA of <i>Japonica</i> polished rice and starch

description: We searched for the easy and simple method to measure the novel indicators which reflect not only AAC, but also (RS) based on pasting properties using RVA. Novel indexes such as SB/Con and Max/Fin (Maximum viscosity/Minimum viscosity) ratios had a very high correlation with proportion of intermediate and long chains of amylopectin; Fb<sub>1+2+3</sub> (DP ≧ 13). In <i>Japonica</i> polished rice, estimation formulae for AAC and RS content were developed using novel indexes based on pasting properties by RVA, and these equations showed determination coefficients of 0.89 and 0.80 for calibration and 0.71 and 0.75 for validation test. We developed the estimation formulae for AAC and RS content for <i>Japonica</i> starch samples. These equations showed determination coefficients of 0.86 and 1.00 for calibration and 0.76 and 0.83 for validation test, which showed that these equations can be applied to the unknown rice samples.