72 research outputs found
Clustering Analyses of 300,000 Photometrically Classified Quasars--I. Luminosity and Redshift Evolution in Quasar Bias
Using ~300,000 photometrically classified quasars, by far the largest quasar
sample ever used for such analyses, we study the redshift and luminosity
evolution of quasar clustering on scales of ~50 kpc/h to ~20 Mpc/h from
redshifts of z~0.75 to z~2.28. We parameterize our clustering amplitudes using
realistic dark matter models, and find that a LCDM power spectrum provides a
superb fit to our data with a redshift-averaged quasar bias of b_Q =
2.41+/-0.08 () for . This represents a better
fit than the best-fit power-law model (; ). We find b_Q increases with redshift.
This evolution is significant at >99.6% using our data set alone, increasing to
>99.9999% if stellar contamination is not explicitly parameterized. We measure
the quasar classification efficiency across our full sample as a = 95.6 +/-
^{4.4}_{1.9}%, a star-quasar separation comparable with the star-galaxy
separation in many photometric studies of galaxy clustering. We derive the mean
mass of the dark matter halos hosting quasars as MDMH=(5.2+/-0.6)x10^{12}
M_solar/h. At z~1.9 we find a deviation from luminosity-independent
quasar clustering; this suggests that increasing our sample size by a factor of
1.8 could begin to constrain any luminosity dependence in quasar bias at z~2.
Our results agree with recent studies of quasar environments at z < 0.4, which
detected little luminosity dependence to quasar clustering on proper scales >50
kpc/h. At z < 1.6, our analysis suggests that b_Q is constant with luminosity
to within ~0.6, and that, for g < 21, angular quasar autocorrelation
measurements are unlikely to have sufficient statistical power at z < 1.6 to
detect any luminosity dependence in quasars' clustering.Comment: 13 pages, 9 figures, 2 tables; uses amulateapj; accepted to Ap
Stevens-Johnson Syndrome From Combined Allopurinol and Angiotensin-Converting Enzyme Inhibitors: A Narrative Review
Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive evidence of a pharmacokinetic interaction between allopurinol and ACE inhibitors. We were only able to find one case report specifically detailing SJS in a patient on combined ACE inhibitors and allopurinol. While the exact mechanism of the interaction is unclear, those reported cases of severe hypersensitivity reactions suggest a previous history of impaired renal function as a predisposing factor in the development of SJS. The potential risk of SJS with coadministration of ACE inhibitors and allopurinol is a drug-drug interaction that physicians should be aware of. This topic requires additional attention to determine if this drug combination should be avoided entirely in certain patients
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
© 2024 The Authors. Journal of Extracellular Vesicles, published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.Peer reviewe
CMS physics technical design report : Addendum on high density QCD with heavy ions
Peer reviewe
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly
Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations
Purpose
To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics.
Patients and Methods
One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS).
Results
There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO.
Conclusion
Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit
Secondary Structure Analysis of the C-Terminus of Gα-Interacting Vesicle Associated Protein Using Circular Dichroism Spectroscopy
A vast majority of cell signaling is mediated through activation of hetero-trimeric G proteins. Gα-Interacting Vesicle associated protein (GIV) is a non-receptor Guanine nucleotide exchange factor (GEF), which activates Gi family of heterotrimeric G proteins downstream of activated receptor tyrosine kinases (RTKs). GIV’s GEF function is mediated by a stretch of highly conserved ~20 residues, which is followed by a putative SH2-like domain in the C-terminus of the protein. Previous studies have shown that the C-terminal 211 amino acids of GIV (referred to as “GIV-CT” henceforth) are capable of functioning autonomously from its recruitment to the cell surface upon activation of RTKs promoting downstream signals by binding to and activating Gi proteins. However, despite all the functional information and computational predictions, the structural insights into how GIV-CT is able to perform all these functions is missing. Here, we have attempted to probe the structural aspects of GIV-CT using circular dichroism (CD) spectroscopy – the most commonly used method for determining the secondary structure of peptides and proteins. N-terminally His6-tagged GIV-CT wild type (WT) and a phosphomimetic mutant (S1674D; binds and activates Gαi better than the WT) were expressed and purified from E. coli BL21-DE3 cells using Co2+-NTA affinity chromatography followed by cation exchange chromatography. Our preliminary CD spectroscopy analyses showed a random coil profile for GIV-CT WT as well as S1674D mutant, both of which could be induced to adopt an α-helical conformation by addition of trifluoroethanol (TFE). Further analysis of CD spectra to predict secondary structure characteristics was carried out using DichroWeb, an online deconvolution program, which compares CD data for known protein structure to that of unknown protein structure. Wild type GIV-CT secondary structure was predicted to contain 1% α-helix, 19% β-sheet and 47% random coil while our mutant contained 1% α-helix, 19% β-sheet and 43% random coil. β-turn and ‘denatured’ helix and sheet percentages make up the final total of 100% secondary structure. In the presence of TFE, GIV-CT WT and S1674D α-helical content increased to 23% and 25%, respectively. Together, our data suggest that although recombinant GIV-CT may be predominantly in an unstructured state, it likely has a propensity to fold into a regular secondary structure, perhaps upon interacting with a binding partner
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