Procedural Pitfalls: The Eleventh Circuit Holds That the Sentencing Commission’s Policy Statement on Sentence Reduction is Binding on Defendant-Filed Motions

On May 7, 2021, in United States v. Bryant, the United States Court of Appeals for the Eleventh Circuit held that the U.S. Sentencing Commission’s policy statement in Section 1B1.13 of the U.S. Sentencing Guidelines binds defendant-filed motions for compassionate release. In its Application Notes, the policy statement provides four “extraordinary and compelling circumstances” that warrant a sentence reduction. Application Note 1(D) is the “catch-all provision” because it states that judges may grant compassionate release for “other reasons” not specifically listed in the preceding Application Notes. Application Note 1(D) states that the Director of the Bureau of Prisons (BOP) defines all “other reasons” under the catch-all provision that qualify an inmate for compassionate release. Before 2018, only the Director of the BOP could file compassionate release motions under 18 U.S.C. § 3582(c)(1)(A). The First Step Act of 2018 amended the statute to allow defendants to file motions too. Because the policy statement still begins with the phrase “upon motion of the Director of the BOP,” courts have since questioned whether it also applies to defendant-filed motions. In a departure from the holdings of the United States Court of Appeals for the Third, Fourth, Fifth, Sixth, Seventh, Ninth and D.C. Circuits, the Eleventh Circuit decided that the policy statement and its corresponding Application Notes apply to defendant-filed motions for compassionate release. Under this interpretation, only the BOP defines the “other reasons” that warrant compassionate release pursuant to Application Note 1(D). This Comment argues that the Eleventh Circuit was incorrect in its interpretation because it disregarded the plain text of the policy statement and erroneously considered the legislative intent of a different statute

Blatant, Subtle, and Insidious: URM Faculty Perceptions of Discriminatory Practices in Predominantly White Institutions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136705/1/soin12147.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136705/2/soin12147_am.pd

Self-Protective Function of Post-Conflict Bystander Affiliation in Mandrills

Background: Affiliative interactions exchanged between victims of aggression and individuals not involved in the original aggression (bystanders) have been observed in various species. Three hypothetical functions have been proposed for these interactions: consolation, self-protection and substitute reconciliation, but data to test them are scanty. Methodology/Principal Findings: We conducted post-conflict and matched control observations on a captive group of mandrills (Mandrillus sphinx). We found that victims often redirected aggression to bystanders, that they received most affiliation from those bystanders that were frequently the target of redirection, and that bystander affiliation reduced the likelihood of redirection. Bystander affiliation did not reduce the victim\u27s distress (as measured by its scratching rates) and was not received primarily from kin/friends. Finally, bystander affiliation did not reduce the likelihood of renewed aggression from the original aggressor. Conclusions/Significance: These results provide support for the self-protection hypothesis but not for the consolation and substitute reconciliation hypotheses

Investigating the Underlying Causes of Cancer Using Sequencing

Cancer is a genetic disease. All cancers are caused by and dependent on mutations. The widespread adoption of NGS in cancer research has revolutionized the field by allowing us to catalog the variants within and across cancer types. This knowledge was used to create a new taxonomy of cancers, where many tumors are classified by genetic alterations in addition to tissue of origin. Despite the role of NGS in identifying the mutations behind these new classifications, pre-genomic methods such as ISH and IHC are still commonly used in the clinic to identify relevant genetic alterations in tumors.About 20% of tumors worldwide are caused by viruses such as HPV, Epstein-Barr virus and Hepatitis B and C viruses. The virus may act as a mutagen by causing prolonged inflammation or by integration into the host genome. Viral infection can therefore be considered another type of genetic alteration used for the classification of tumors, and indeed some tumors are now classified by their causal viral infections. Epimutations are a type of genetic alteration affects epigenetic marks such as DNA methylation rather than the DNA sequence. Epimutations are the genetic lesions behind several disorders including cancer predisposition syndromes. Here I present my work developing an app that integrates with the UCSF 500 pipeline to detect known oncogenic viral sequences in DNA samples from tumors (Chapter 2). I also present my work analyzing long-read sequencing and methylation data of a patient with bilateral Wilms tumor to identify the epimutation causing their cancer predisposition syndrome previously missed by other technologies (Chapter 3). My work reflects the utility of adapting state-of-the-art sequencing technologies for diagnostic use in the clinic. H3K27M gliomas have a mutation in the genes encoding histone H3 that interferes with the deposition of the repressive epigenetic mark H3K27me3. This mark is important in regulating cell type development and EMT. In Chapter 4 I present my work using gene expression analysis to identify the role of EMT in the development and oncogenesis of H3K27M gliomas. Aberrant EMT may serve as a key dependency of these tumors

Time reallocation in a multiresponse environment: Effects of restricting response classes

Four adult male rats were each placed for three hours daily into an apparatus that provided individual compartments for six separate location-defined responses. The available responses consisted of: (1) the opportunity to turn off room lighting, producing darkness; (2) the opportunity to view a female rat; (3) the opportunity to turn off white noise; (4) the opportunity to drink; (5) the opportunity to eat; and (6) “other,” representing time in the hallway between compartments. Each subject underwent a series of conditions characterized as an A-B-A-C-A design. Manipulations consisted of the removal of a low-probability response (darkness) and of a high-probability response (escape from noise) in a counter-balanced manner across subjects. The dependent measure for all subjects was the percentage of total session time spent in each compartment. Four predictive rules concerning the redistribution of behavior after response restriction were tested, including the constant-ratio rule, equal time redistribution, the most probable alternative, and the sequential-dependency rule. The results indicate no support for any of the four predictive rules and suggest that empirical assessment of restriction effects is necessary in reinforcement studies involving temporally extended responses

Clinically relevant mutations in core metabolic genes confer antibiotic resistance

© 2021 American Association for the Advancement of Science. All rights reserved. Although metabolism plays an active role in antibiotic lethality, antibiotic resistance is generally associated with drug target modification, enzymatic inactivation, and/or transport rather than metabolic processes. Evolution experiments of Escherichia coli rely on growth-dependent selection, which may provide a limited view of the antibiotic resistance landscape. We sequenced and analyzed E. coli adapted to representative antibiotics at increasingly heightened metabolic states. This revealed various underappreciated noncanonical genes, such as those related to central carbon and energy metabolism, which are implicated in antibiotic resistance. These metabolic alterations lead to lower basal respiration, which prevents antibiotic-mediated induction of tricarboxylic acid cycle activity, thus avoiding metabolic toxicity and minimizing drug lethality. Several of the identified metabolism-specific mutations are overrepresented in the genomes of >3500 clinical E. coli pathogens, indicating clinical relevance