The khmer software package: enabling efficient nucleotide sequence analysis

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(-/-) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(-/-) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/-) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/-) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(-/-) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation

The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

The Law and Psychology of Suspicion and Police Decision-Making

Police officers decide to detain and search civilians under uncertainty and risk, and both false positive and false negative errors can be costly. The courts apply the reasonable suspicion standard of proof to evaluate the constitutionality of nonconsensual stops and searches, placing an ambiguous and subjective assessment of a poorly understood psychological state at the center of laws, policies, and trainings on police-civilian contact. The law and psychology of suspicion may have important effects on the frequency, accuracy, and reporting of policing decisions. Investigating those effects requires an understanding of the policy landscape of police decision-making and the basic psychology of suspicion. In this dissertation, I explore suspicion as a legal concept and as a psychological experience. I describe the role of the reasonable suspicion standard in judicial evaluations of the constitutionality of police practices, and the implications for the guidelines and trainings that agencies provide to officers. I contend that legal and quantitative analyses of policing practices should incorporate an understanding of the psychology of individual decision-making and the incentives created by the regulatory environment. The constitutional analysis assumes that civilian behavior, situational circumstances, and prior knowledge all affect an officer’s experience of suspicion and subsequent actions. Very little is known, however, about the basic psychology of suspicion and how it might affect judgment and decision-making. I investigate the psychological properties and covariates of interpersonal suspicion as reported by lay participants in a series of studies, establishing a baseline to which I will compare the effects of training and professional experience in future research. Using latent variable models and automated text analyses, I find that during experiences of interpersonal suspicion of a stranger, people tend to question the stranger’s intentions and experience intuition, attentiveness, and wariness. In these situations, distrust is more closely associated with emotional arousal than interpersonal suspicion. On average, female participants report slightly higher situational interpersonal suspicion relative to male participants, and participants who identify as Black or African American report lower suspicion relative to those who identify as White, Latino, or Hispanic. Relative to participants, the people who are targets of situational suspicion are more often described as male, Black, and Latino. On average, participants report a similar degree of suspicion across perceived target gender and racial categories, but there are significant differences among the associated emotions, inferences, and behavioral responses. Participants describing male and Black targets report experiencing greater fear and believing that the target’s behavior was dangerous. Participants describing male targets are more likely to report inferring that the target’s behavior was criminal, relative to participants describing female targets.The dispositional tendency toward interpersonal suspicion is associated with neuroticism and low agreeableness in two samples of university students, and these findings are insensitive to variations in measurement instruments. In a simulation where university students take on the role of a police officer and report their suspicion in response to either Black or White male targets, I find that aggregate measures of dispositional interpersonal suspicion are uncorrelated with ratings of situational suspicion in response to the stimuli, which do not differ significantly by race of the target. An exploratory analysis suggests that dispositional suspicion, as measured by a single item, is associated with higher ratings of situational suspicion in response to White targets only.My findings suggest that during experiences of interpersonal suspicion of strangers, people tend to question the stranger’s intentions and experience intuition, attentiveness, and wariness, and that the type of cognitive arousal associated with suspicion may be context-specific. In the concluding discussion, I also identify findings that could be particularly relevant in the legal context, including the salience of intuition in experiences of suspicion and the variation associated with target race in the correlates of suspicion. I aim to advance the current understanding of suspicion and establish a foundation for future research on its role in legal decision-making

The Law and Psychology of Suspicion and Police Decision-Making

Police officers decide to detain and search civilians under uncertainty and risk, and both false positive and false negative errors can be costly. The courts apply the reasonable suspicion standard of proof to evaluate the constitutionality of nonconsensual stops and searches, placing an ambiguous and subjective assessment of a poorly understood psychological state at the center of laws, policies, and trainings on police-civilian contact. The law and psychology of suspicion may have important effects on the frequency, accuracy, and reporting of policing decisions. Investigating those effects requires an understanding of the policy landscape of police decision-making and the basic psychology of suspicion. In this dissertation, I explore suspicion as a legal concept and as a psychological experience. I describe the role of the reasonable suspicion standard in judicial evaluations of the constitutionality of police practices, and the implications for the guidelines and trainings that agencies provide to officers. I contend that legal and quantitative analyses of policing practices should incorporate an understanding of the psychology of individual decision-making and the incentives created by the regulatory environment. The constitutional analysis assumes that civilian behavior, situational circumstances, and prior knowledge all affect an officer’s experience of suspicion and subsequent actions. Very little is known, however, about the basic psychology of suspicion and how it might affect judgment and decision-making. I investigate the psychological properties and covariates of interpersonal suspicion as reported by lay participants in a series of studies, establishing a baseline to which I will compare the effects of training and professional experience in future research. Using latent variable models and automated text analyses, I find that during experiences of interpersonal suspicion of a stranger, people tend to question the stranger’s intentions and experience intuition, attentiveness, and wariness. In these situations, distrust is more closely associated with emotional arousal than interpersonal suspicion. On average, female participants report slightly higher situational interpersonal suspicion relative to male participants, and participants who identify as Black or African American report lower suspicion relative to those who identify as White, Latino, or Hispanic. Relative to participants, the people who are targets of situational suspicion are more often described as male, Black, and Latino. On average, participants report a similar degree of suspicion across perceived target gender and racial categories, but there are significant differences among the associated emotions, inferences, and behavioral responses. Participants describing male and Black targets report experiencing greater fear and believing that the target’s behavior was dangerous. Participants describing male targets are more likely to report inferring that the target’s behavior was criminal, relative to participants describing female targets. The dispositional tendency toward interpersonal suspicion is associated with neuroticism and low agreeableness in two samples of university students, and these findings are insensitive to variations in measurement instruments. In a simulation where university students take on the role of a police officer and report their suspicion in response to either Black or White male targets, I find that aggregate measures of dispositional interpersonal suspicion are uncorrelated with ratings of situational suspicion in response to the stimuli, which do not differ significantly by race of the target. An exploratory analysis suggests that dispositional suspicion, as measured by a single item, is associated with higher ratings of situational suspicion in response to White targets only. My findings suggest that during experiences of interpersonal suspicion of strangers, people tend to question the stranger’s intentions and experience intuition, attentiveness, and wariness, and that the type of cognitive arousal associated with suspicion may be context-specific. In the concluding discussion, I also identify findings that could be particularly relevant in the legal context, including the salience of intuition in experiences of suspicion and the variation associated with target race in the correlates of suspicion. I aim to advance the current understanding of suspicion and establish a foundation for future research on its role in legal decision-making

Sequencing Primer

<p>This is a presentation showing the various popular sequencing technolgies that are widely available in mid-2015</p