Principles to Guide the Office of Legal Counsel

Former members of Office of Legal Counsel ( OLC ) in the Department of Justice offer guidance for their successors. Among the document\u27s recommendations are suggestions that the OLC provide an accurate and honest appraisal of applicable law, even if that advice will constrain the administration’s pursuit of desired policies; and publicly disclose its written legal opinions in a timely manner, absent strong reasons for delay or nondisclosure

Developing Cyberspace Data Understanding Using CRISP-DM for Host-based IDS Feature Mining

Current intrusion detection systems (IDS) generate a large number of specific alerts, but typically do not provide actionable information. Compounding this problem is the fact that many alerts are false positive alerts. This paper applies the Cross Industry Standard Process for Data Mining (CRISP-DM) to develop an understanding of a host environment under attack. Data is generated by launching scans and exploits at a machine outfitted with a set of host-based forensic data collectors. Through knowledge discovery, features are selected to project human understanding of the attack process into the IDS model. By discovering relationships between the data collected and controlled events, false positive alerts were reduced by over 91% when compared to a leading open source IDS. This method of searching for hidden forensic evidence relationships enhances understanding of novel attacks and vulnerabilities, bolstering ones ability to defend the cyberspace domain. The methodology presented can be used to further host-based intrusion detection research

Feeding traces attributable to juvenile Tyrannosaurus rex offer insight into ontogenetic dietary trends

Theropod dinosaur feeding traces and tooth marks yield paleobiological and paleoecological implications for social interactions, feeding behaviors, and direct evidence of cannibalism and attempted predation. However, ascertaining the taxonomic origin of a tooth mark is largely dependent on both the known regional biostratigraphy and the ontogenetic stage of the taxon. Currently, most recorded theropod feeding traces and bite marks are attributed to adult theropods, whereas juvenile and subadult tooth marks have been rarely reported in the literature. Here we describe feeding traces attributable to a late-stage juvenile Tyrannosaurus rex on a caudal vertebra of a hadrosaurid dinosaur. The dimensions and spacing of the traces were compared to the dentition of Tyrannosaurus rex maxillae and dentaries of different ontogenetic stages. These comparisons reveal that the tooth marks present on the vertebra closely match the maxillary teeth of a late-stage juvenile Tyrannosaurus rex specimen histologically determined to be 11–12 years of age. These results demonstrate that late-stage juvenile and subadult tyrannosaurs were already utilizing the same large-bodied food sources as adults despite lacking the bone-crushing abilities of adults. Further identification of tyrannosaur feeding traces coupled with experimental studies of the biomechanics of tyrannosaur bite forces from younger ontogenetic stages may reveal dynamic dietary trends and ecological roles of Tyrannosaurus rex throughout ontogeny

CALIBRATING DIVERGENCE TIMES ON SPECIES TREES VERSUS GENE TREES: IMPLICATIONS FOR SPECIATION HISTORY OF APHELOCOMA JAYS

Estimates of the timing of divergence are central to testing the underlying causes of speciation. Relaxed molecular clocks and fossil calibration have improved these estimates; however, these advances are implemented in the context of gene trees, which can overestimate divergence times. Here we couple recent innovations for dating speciation events with the analytical power of species trees, where multilocus data are considered in a coalescent context. Divergence times are estimated in the bird genus Aphelocoma to test whether speciation in these jays coincided with mountain uplift or glacial cycles. Gene trees and species trees show general agreement that diversification began in the Miocene amid mountain uplift. However, dates from the multilocus species tree are more recent, occurring predominately in the Pleistocene, consistent with theory that divergence times can be significantly overestimated with gene-tree based approaches that do not correct for genetic divergence that predates speciation. In addition to coalescent stochasticity, Haldane's rule could account for some differences in timing estimates between mitochondrial DNA and nuclear genes. By incorporating a fossil calibration applied to the species tree, in addition to the process of gene lineage coalescence, the present approach provides a more biologically realistic framework for dating speciation events, and hence for testing the links between diversification and specific biogeographic and geologic events.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79292/1/j.1558-5646.2010.01097.x.pd

The use of fluorescent probes to characterize conformational changes in the interaction between vitronectin and plasminogen activator inhibitor-1

Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type plasminogen activator and urokinase, is known to convert readily to a latent form by insertion of the reactive center loop into a central β- sheet. Interaction with vitronectin stabilizes PAI-1 and decreases the rate of conversion to the latent form, but conformational effects of vitronectin on the reactive center loop of PAI-1 have not been documented. Mutant forms of PAI-1 were designed with a cysteine substitution at either position P1\u27 or P9 of the reactive center loop. Labeling of the unique cysteine with a sulfhydryl-reactive fluorophore provides a probe that is sensitive to vitronectin binding. Results indicate that the scissile P1-P1\u27 bond of PAI-1 is more solvent exposed upon interaction with vitronectin, whereas the N- terminal portion of the reactive loop does not experience a significant change in its environment. These results were complemented by labeling vitronectin with an arginine-specific coumarin probe which compromises heparin binding but does not interfere with PAI-1 binding to the protein. Dissociation constants of approximately 100 nM are calculated for the vitronectin/PAI-1 interaction from titrations using both fluorescent probes. Furthermore, experiments in which PAI-1 failed to compete with heparin for binding to vitronectin argue for separate binding sites for the two ligands on vitronectin

Chiasma

Newspaper reporting on events at the Boston University School of Medicine in the 1960s

Bite Force Estimates in Juvenile Tyrannosaurus Rex Based on Simulated Puncture Marks

BACKGROUND: Bite marks attributed to adult Tyrannosaurus rex have been subject to numerous studies. However, few bite marks attributed to T. rex have been traced to juveniles, leaving considerable gaps in understanding ontogenetic changes in bite mechanics and force, and the paleoecological role of juvenile tyrannosaurs in the late Cretaceous. METHODS: Here we present bite force estimates for a juvenile Tyrannosaurus rex based on mechanical tests designed to replicate bite marks previously attributed to a T. rex of approximately 13 years old. A maxillary tooth of the juvenile Tyrannosaurus specimen BMR P2002.4.1 was digitized, replicated in dental grade cobalt chromium alloy, and mounted to an electromechanical testing system. The tooth was then pressed into bovine long bones in various locations with differing cortical bone thicknesses at varying speeds for a total of 17 trials. Forces required to replicate punctures were recorded and puncture dimensions were measured. RESULTS: Our experimentally derived linear models suggest bite forces up to 5,641.19 N from cortical bone thickness estimated from puncture marks on an Edmontosaurus and a juvenile Tyrannosaurus. These findings are slightly higher than previously estimated bite forces for a juvenile Tyrannosaurus rex of approximately the same size as BMR P2002.4.1 but fall within the expected range when compared to estimates of adult T. rex. DISCUSSION: The results of this study offer further insight into the role of juvenile tyrannosaurs in late Cretaceous ecosystems. Furthermore, we discuss the implications for feeding mechanisms, feeding behaviors, and ontogenetic niche partitioning

Medical Student Milestones in Emergency Medicine

Objectives Medical education is a continuum from medical school through residency to unsupervised clinical practice. There has been a movement toward competency‐based medical education prompted by the Accreditation Council for Graduate Medical Education ( ACGME ) using milestones to assess competence. While implementation of milestones for residents sets specific standards for transition to internship, there exists a need for the development of competency‐based instruments to assess medical students as they progress toward internship. The objective of this study was to develop competency‐based milestones for fourth‐year medical students completing their emergency medicine ( EM ) clerkships (regardless of whether the students were planning on entering EM ) using a rigorous method to attain validity evidence. Methods A literature review was performed to develop a list of potential milestones. An expert panel, which included a medical student and 23 faculty members (four program directors, 16 clerkship directors, and five assistant deans) from 19 different institutions, came to consensus on these milestones through two rounds of a modified Delphi protocol. The Delphi technique builds content validity and is an accepted method to develop consensus by eliciting expert opinions through multiple rounds of questionnaires. Results Of the initial 39 milestones, 12 were removed at the end of round 1 due to low agreement on importance of the milestone or because of redundancy with other milestones. An additional 12 milestones were revised to improve clarity or eliminate redundancy, and one was added based on expert panelists' suggestions. Of the 28 milestones moving to round 2, consensus with a high level of agreement was achieved for 24. These were mapped to the ACGME EM residency milestone competency domains, as well as the Association of American Medical Colleges ( AAMC ) core entrustable professional activities for entering residency to improve content validity. Conclusions This study found consensus support by experts for a list of 24 milestones relevant to the assessment of fourth‐year medical student performance by the completion of their EM clerkships. The findings are useful for development of a valid method for assessing medical student performance as students approach residency. Resumen Objetivos La formación médica es un continuo que va desde la universidad, pasando por la residencia, hasta la práctica clínica no supervisada. Ha habido un movimiento hacia la formación médica basada en la adquisición de competencias promovido por el Accreditation Council for Graduate Medical Education ( ACGME ) mediante los hitos para evaluar la competencia. Mientras la implementación de los hitos para los residentes establece normas específicas para la transición a residente, existe necesidad de desarrollar instrumentos basados en la competencia para evaluar a los estudiantes de medicina según progresan hacia la residencia. El objetivo de este estudio fue desarrollar los hitos basados ​​en competencias para los estudiantes de medicina de cuarto año al completar sus prácticas clínicas en Medicina de Urgencias y Emergencias ( MUE ) (indistintamente si el estudiante planeaba acceder a la MUE ) utilizando un método riguroso para lograr evidencia válida. Metodología Se realizó una revisión de la literatura para desarrollar una lista de hitos potenciales. Un panel de expertos, que incluyó 23 profesores de la facultad cuyas responsabilidades eran directores de programa (4), directores de prácticas clínicas (16), vicedecanos (5) y un estudiante de medicina de 19 instituciones diferentes, llegaron a un consenso sobre estos hitos a través de 2 rondas del protocolo de Delphi modificado. La técnica Delphi construye un contenido válido y es un método aceptado para desarrollar un consenso mediante la obtención de opiniones de expertos a través de múltiples rondas de preguntas. Resultados De los 39 hitos iniciales, se eliminaron 12 al final de la primera ronda debido al bajo acuerdo sobre la importancia del hito o debido a su redundancia con otros hitos. Se revisaron 12 hitos adicionales para mejorar la claridad o eliminar la redundancia, y se añadió uno basado en las sugerencias del panel de expertos. De los 28 hitos que llegaron a la segunda ronda, se alcanzó un consenso con un alto nivel de acuerdo para 24 de los hitos. Estos hitos se esquematizaron a los dominios de competencia de los hitos de la residencia de MUE del ACGME , así como a las actividades profesionales recomendadas para acceder a la residencia de la Association of American Medical Colleges ( AAMC ) para mejorar la validez de contenido. Conclusiones Este estudio llegó a un consenso apoyado por expertos para una lista de 24 hitos relevantes para evaluar el rendimiento de los estudiantes de medicina de cuarto año al finalizar su práctica clínica en MUE . Los hallazgos son útiles para el desarrollo de un método válido para evaluar el rendimiento de los estudiantes de medicina a medida que éstos se acercan a la residencia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108261/1/acem12443-sup-0002-DataSupplementS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108261/2/acem12443.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108261/3/acem12443-sup-0001-DataSupplementS1.pd

Characterization of an Extensive Interface on Vitronectin for Binding to Plasminogen Activator Inhibitor-1: Adoption of Structure in an Intrinsically Disordered Region

Copyright © 2019 American Chemical Society. Small-angle neutron scattering (SANS) measurements were pursued to study human vitronectin, a protein found in tissues and the circulation that regulates cell adhesion/migration and proteolytic cascades that govern hemostasis and pericellular proteolysis. Many of these functions occur via interactions with its binding partner, plasminogen activator inhibitor-1 (PAI-1), the chief inhibitor of proteases that lyse and activate plasminogen. We focused on a region of vitronectin that remains uncharacterized from previous X-ray scattering, nuclear magnetic resonance, and computational modeling approaches and which we propose is involved in binding to PAI-1. This region, which bridges the N-terminal somatomedin B (SMB) domain with a large central β-propeller domain of vitronectin, appears unstructured and has characteristics of an intrinsically disordered domain (IDD). The effect of osmolytes was evaluated using circular dichroism and SANS to explore the potential of the IDD to undergo a disorder-to-order transition. The results suggest that the IDD favors a more ordered structure under osmotic pressure; SANS shows a smaller radius of gyration (Rg) and a more compact fold of the IDD upon addition of osmolytes. To test whether PAI-1 binding is also coupled to folding within the IDD structure, a set of SANS experiments with contrast variation were performed on the complex of PAI-1 with a vitronectin fragment corresponding to the N-terminal 130 amino acids (denoted the SMB-IDD because it contains the SMB domain and IDD in linear sequence). Analysis of the SANS data using the Ensemble Optimization Method confirms that the SMB-IDD adopts a more compact configuration when bound to PAI-1. Calculated structures for the PAI-1:SMB-IDD complex suggest that the IDD provides an interaction surface outside of the primary PAI-1-binding site located within the SMB domain; this binding is proposed to lead to the assembly of higher-order structures of vitronectin and PAI-1 commonly found in tissues