In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was c... more This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC.
The convective–dispersive, or advective–dispersive, equation (CDE) has long been the model of cho... more The convective–dispersive, or advective–dispersive, equation (CDE) has long been the model of choice for solute transport in soils. Using the average concentration of soluble salts in soil profile to evaluate changes in salinity due to irrigation can be beneficial when spatial variability of soil salinity at selected depths is larger than spatial variability of soil salinity in the layer encompassing these depths, and when soil salinity is evaluated with electric conductivity measurements that give layer-average rather than depth-specific salinity values. The objective of this work was to present analytical solutions of the CDE that express the average soluble salt content in soil profile as the function of time, water flux, and solute dispersion parameter. The solutions were developed for both semiinfinite and finite domain and implemented in a computer code. Examples are presented of using these solutions to develop a nomogram for the dispersion coefficient estimation and to evaluate the applicability of the semiinfinite domain solution to soil monolith leaching experiments. In cases when the CDE application is justified, the analysis of the salt leaching based on the average salt concentrations in soil profile provides estimates of the effective salt dispersion parameter useful in land evaluation and soil reclamation.
A metal-matrix specimen was investigated using moiré interferometry with 2400 ℓ/mm (60,960 ℓ/in.)... more A metal-matrix specimen was investigated using moiré interferometry with 2400 ℓ/mm (60,960 ℓ/in.). The specimen was a 6-ply [0/±45]s boron-aluminum tensile coupon with a central slot. The unequal deformations in fibers and matrix were evident. Special attention was given to a plastic slip zone in the matrix. Normal and shear strains were calculated in the slip zone; the shear-strain concentration factor rose dramatically with the onset of plastic slip and continued to rise gradually with load to 95 percent of the failure load. The precipitous change from maximum tensile strain in one fiber to zero tensile strain in the neighboring fiber was accommodated by the very high shear strain in the matrix in the slip zone. Experimental considerations are discussed: shear strains are independent of rigid-body rotations; simplified strain calculations are justified; averaging across the narrow slip region and the influence of finite thickness of the specimen grating contribute to underestimation of peak strains.
A measurement of the multi-strange Xi- and Omega- baryons and their antiparticles by the ALICE ex... more A measurement of the multi-strange Xi- and Omega- baryons and their antiparticles by the ALICE experiment at the CERN Large Hadron Collider (LHC) is presented for proton-proton collisions at centre of mass energy of 7 TeV. The transverse momentum (pt) distributions were studied at mid-rapidity (|y|…
The ALICE experiment at the LHC has studied inclusive J/psi production at central and forward rap... more The ALICE experiment at the LHC has studied inclusive J/psi production at central and forward rapidities in pp collisions at sqrt(s) = 7 TeV. In this Letter, we report on the first results obtained detecting the J/psi through its dilepton decay into e+e- and mu+mu- pairs in the rapidity range…
Journal of Fluids Engineering-transactions of The Asme, 2001
Page 1. 1 A Proposed Paper Submitted to the ASME Journal of Fluids Engineering Hydrodynamic Focus... more Page 1. 1 A Proposed Paper Submitted to the ASME Journal of Fluids Engineering Hydrodynamic Focusing for a Micromachined Flow Cytometer by Gwo-Bin Lee*, Chen-I Hung + , Bin-Jo Ke +a , Guan-Ruey Huang* a , Bao-Herng Hwei* b , Hui-Fang Lai* b ...
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was c... more This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC.
The convective–dispersive, or advective–dispersive, equation (CDE) has long been the model of cho... more The convective–dispersive, or advective–dispersive, equation (CDE) has long been the model of choice for solute transport in soils. Using the average concentration of soluble salts in soil profile to evaluate changes in salinity due to irrigation can be beneficial when spatial variability of soil salinity at selected depths is larger than spatial variability of soil salinity in the layer encompassing these depths, and when soil salinity is evaluated with electric conductivity measurements that give layer-average rather than depth-specific salinity values. The objective of this work was to present analytical solutions of the CDE that express the average soluble salt content in soil profile as the function of time, water flux, and solute dispersion parameter. The solutions were developed for both semiinfinite and finite domain and implemented in a computer code. Examples are presented of using these solutions to develop a nomogram for the dispersion coefficient estimation and to evaluate the applicability of the semiinfinite domain solution to soil monolith leaching experiments. In cases when the CDE application is justified, the analysis of the salt leaching based on the average salt concentrations in soil profile provides estimates of the effective salt dispersion parameter useful in land evaluation and soil reclamation.
A metal-matrix specimen was investigated using moiré interferometry with 2400 ℓ/mm (60,960 ℓ/in.)... more A metal-matrix specimen was investigated using moiré interferometry with 2400 ℓ/mm (60,960 ℓ/in.). The specimen was a 6-ply [0/±45]s boron-aluminum tensile coupon with a central slot. The unequal deformations in fibers and matrix were evident. Special attention was given to a plastic slip zone in the matrix. Normal and shear strains were calculated in the slip zone; the shear-strain concentration factor rose dramatically with the onset of plastic slip and continued to rise gradually with load to 95 percent of the failure load. The precipitous change from maximum tensile strain in one fiber to zero tensile strain in the neighboring fiber was accommodated by the very high shear strain in the matrix in the slip zone. Experimental considerations are discussed: shear strains are independent of rigid-body rotations; simplified strain calculations are justified; averaging across the narrow slip region and the influence of finite thickness of the specimen grating contribute to underestimation of peak strains.
A measurement of the multi-strange Xi- and Omega- baryons and their antiparticles by the ALICE ex... more A measurement of the multi-strange Xi- and Omega- baryons and their antiparticles by the ALICE experiment at the CERN Large Hadron Collider (LHC) is presented for proton-proton collisions at centre of mass energy of 7 TeV. The transverse momentum (pt) distributions were studied at mid-rapidity (|y|…
The ALICE experiment at the LHC has studied inclusive J/psi production at central and forward rap... more The ALICE experiment at the LHC has studied inclusive J/psi production at central and forward rapidities in pp collisions at sqrt(s) = 7 TeV. In this Letter, we report on the first results obtained detecting the J/psi through its dilepton decay into e+e- and mu+mu- pairs in the rapidity range…
Journal of Fluids Engineering-transactions of The Asme, 2001
Page 1. 1 A Proposed Paper Submitted to the ASME Journal of Fluids Engineering Hydrodynamic Focus... more Page 1. 1 A Proposed Paper Submitted to the ASME Journal of Fluids Engineering Hydrodynamic Focusing for a Micromachined Flow Cytometer by Gwo-Bin Lee*, Chen-I Hung + , Bin-Jo Ke +a , Guan-Ruey Huang* a , Bao-Herng Hwei* b , Hui-Fang Lai* b ...
Uploads