Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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. For example, 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 versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost 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 fi eld 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. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. 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. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. 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

Corporate Culture In Financial Markets

Corporate culture within financial institutions relates to the extent to which norms and values within promote regulatory objectives to protect investor welfare and promote market integrity. Using hand-collected measures of corporate culture based on U.S. security code violations issued by the Financial Industry Regulatory Authority (FINRA), I examine how corporate culture relates to financial institutions' roles as information intermediaries in capital markets. Analysts employed by financial institutions with weaker corporate cultures produce less accurate forecasts, more strategically biased forecasts, and less informative reports. These findings offer important implications for regulators regarding the role of cultural forces in financial institutions

Development of an actuated traffic control process utilizing real-time estimated volume feedbback

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 79-80).Issued also on microfiche from Lange Micrographics.Actuated traffic controllers are intended to determine traffic conditions, in real-time by means of vehicle detection, and respond accordingly in order to maintain the highest reasonable level of efficiency under varying conditions. However, modern traffic controllers are essentially sophisticated electronic timers. Rather than merely responding to detector ablations, it is desirable to improve this system such that the controller has a goal to be achieved and acquires information about the present state of the system in the same units. The goal of this research was to develop an actuated traffic control process that could use estimated volumes in order to optimally operate the traffic signal in real- time in response to actual traffic demands, or a reasonable estimate of demand. Once the present and desired states of the system are known, the control changes necessary to move from the present state to the optimal target state can be determined. A further goal of this research was to establish the relationship between the traditional control parameter, passage gap and key operating parameters, in order to allow changes in signal operations to be made by means of passage gap adjustments. The relationships between passage gap and cycle length, green splits, and interval length were studied, and the cycle length relationship was formalized mathematically. The quantified form can then be used as a tool to adjust the signal performance to approach the desired operating state. Research was conducted with computer simulation, using both stand-alone software and a hardware-in-the-loop setup. Testing and comparison between methods validated the use of these models. Results indicated that the volume estimation methodology could be readily calibrated to provide good estimates of traffic volumes by movement. Furthermore, simulation results quantified the relationship between passage gap and cycle length, thereby establishing a mechanism by which to directly implement signal operating changes at an actuated traffic signal. The scope of the research dealt with only one traffic control sensor design configuration - that of 6th-foot stapling detection. The overall study results suggest that this design is operationally very efficient for minimizing delay, but provides little "dilemma zone'' protection for arriving motorists at low-volumes and high-speeds. The research results suggest that the operational results may have been different had other high-speed detection options been considered. This thesis also includes descriptions of lessons learned through the simulation process and recommendations for issues to be addressed in future research

Modulation of hippocampal synaptic transmission: Effects of stimulus patterns and glutamate agonists.

Modulation of hippocampal synaptic transmission: Effects of stimulus patterns and glutamate agonists

Countercyclical prudential buffers and bank risk-taking

We investigate the effects of countercyclical prudential buffers on bank risk-taking. We exploit the introduction of dynamic loan loss provisioning in Spain, mandating that banks use historical average loss rates in their estimation of loan loss provisions. We find that dynamic loan loss provisioning is associated with reductions in timely loan loss provisioning. Banks that previously recognized loan losses in a timely fashion exhibit the greatest reductions in timeliness and consequently extend loans to riskier borrowers with lower accounting quality. Our results have policy implications for the debate on the use of financial reporting requirements in mitigating capital pro-cyclicality

Do Jobseekers Value Diversity Information? Evidence from a Field Experiment

We examine how information about the diversity of a potential employer’s workforce affects individuals’ job-seeking behavior. We embed a field experiment in job recommendation emails sent from a leading career advice agency in the U.S. The experimental treatment involves highlighting a diversity metric to jobseekers. Our results indicate that disclosing diversity scores in job postings increases the click-through rates of jobseekers for firms with higher diversity scores, with such effects varying across jobseeker demographics. A follow-up survey provides some evidence on the potential explanations for why jobseekers value diversity information. We further examine how jobseekers’ preferences for diversity relate to disclosure choices under the U.S. SEC Human Capital Disclosure requirement. We find that firms in industries characterized by higher jobseeker responsiveness to diversity information tend to voluntarily disclose diversity metrics in their 10-Ks under these new disclosure requirements

Do Jobseekers Value Diversity Information? Evidence from a Field Experiment

We examine how information about the diversity of a potential employer’s workforce affects individuals’ job-seeking behavior, and whether workers’ preferences explain corporate disclosure decisions. We embed a field experiment in job recommendation emails sent from a leading career advice agency in the U.S. The experimental treatment involves highlighting a diversity metric to jobseekers. Studying 267,494 unique jobseekers, we find that disclosing diversity scores in job postings increases the click-through rate of jobseekers for firms with higher diversity scores. These effects are more pronounced for female and entry-level jobseekers. We estimate that jobseekers update their willingness to pay (WTP) for a firm’s diversity by $1,463 when faced with a 10% increase in diversity scores relative to the interquartile range. We conduct a follow-up survey with jobseekers to better understand why diversity information was useful to them. Finally, we document that firms in industries characterized by higher jobseeker responsiveness to diversity information tend to voluntarily disclosure diversity metrics in their 10-Ks under new SEC disclosure requirements. That is, disclosure choices partially reflect ‘jobseeker materiality.’ Overall, our findings generate important insights regarding jobseekers’ demand for diversity information