Bitcoin: Order Without Law in the Digital Age

Modern law makes currency a creature of the state and ultimately the value of its currency depends on the public’s trust in that state. While some nations are more capable than others at instilling public trust in the stability of their monetary institutions, it is nonetheless impossible for any legal system to make the pre-commitments necessary to completely isolate the governance of its money supply from political pressure. This proposition is true not only today, where nearly all government institutions manage their money supply in the form of central banking, but also true of past private banking regimes circulating their notes under the shadow of public law. However, bitcoin represents a potential third currency regime far more resistant to state control because it mints currency units that exist in no physical place, places a numerical ceiling on the number of units that can be created, and relies on scientific principles from cryptography to guarantee that ceiling and verify any person-to-person transfer. The trust required is not in any government but in the decentralized order of those who verify bitcoin transactions and those who create the software these verifiers choose to run on their connected computers. This Article explores the fundamental structure of bitcoin, first by demystifying it as a technology, and second by showing how its decentralized order contrasts with other currency regimes. Unlike governments that use the power of law to compel action, bitcoin relies on a system of built-in incentives to encourage behavior that benefits not only those seeking to use bitcoin, but also bitcoin miners—those who voluntarily undertake the task of maintaining the payment network. While currently bitcoin is too volatile to compete with all but the worst government-issued currencies, the qualities of this system may give bitcoin a long-term advantage over many currencies. As the bitcoin ecosystem continues to grow, its nonlegal order can help it climb the rungs of stability created by distrust in government. The technology underpinning bitcoin is the next point of innovation in the digital age—the same era that has already seen software create institutional disruption from Amazon, Facebook, and Uber, among many others. As bitcoin gains in popularity, it offers a platform for other kinds of technological alternatives to traditional legal regimes, like smart contracts. Bitcoin’s order without currency law will facilitate other forms of order with less law. This is a propitious time for fundamental examination of bitcoin. Despite experiencing significant speculation and volatility throughout late 2017 and early 2018, its ten-year history demonstrates a downward trend in volatility and an upward trend in market capitalization

Intrinsic regulation of quiescence and radioresistance in intestinal stem cells

The intestinal epithelium regenerates every 5-7 days, a process that is facilitated by a pool of intestinal stem cells. Over the past decade, it has become apparent that the intestinal stem cell pool is diverse, containing at least two populations. Active stem cells (aISCs) are moderately proliferative and contribute to homeostatic regeneration, while reserve stem cells (rISCs) are slowly proliferative and facilitate regeneration following damage-induced loss of the aISC population. The genetic mechanisms required for the production and maintenance of rISCs are unknown. Sox9 is a transcription factor that has been shown to maintain stem cell populations in various tissues. In the intestinal epithelium, Sox9 is expressed in a gradient that negatively correlates with proliferative capacity. Transit-amplifying progenitors express the lowest levels of Sox9, while aISCs express intermediate levels, and cells expressing the highest levels of Sox9 are consistent with slowly cycling rISCs. In this dissertation, I will address the role that Sox9 plays in maintaining rISC function within the intestinal epithelium. I find that Sox9 is not only necessary for the production of a quiescent rISCs, but that it is also uniformly necessary for maintaining radioresistance within the rISC pool. This work identifies Sox9 as a novel intrinsic regulator of the rISC state.Doctor of Philosoph

How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Next generation genomic sequencing technologies (including whole genome or whole exome sequencing) are being increasingly applied to clinical care. Yet, the breadth and complexity of sequencing information raise questions about how best to communicate and return sequencing information to patients and families in ways that facilitate comprehension and optimal health decisions. Obtaining answers to such questions will require multidisciplinary research. In this paper, we focus on how psychological science research can address questions related to clinical genomic sequencing by explaining emotional, cognitive, and behavioral processes in response to different types of genomic sequencing information (e.g., diagnostic results and incidental findings). We highlight examples of psychological science that can be applied to genetic counseling research to inform the following questions: (1) What factors influence patients’ and providers’ informational needs for developing an accurate understanding of what genomic sequencing results do and do not mean?; (2) How and by whom should genomic sequencing results be communicated to patients and their family members?; and (3) How do patients and their families respond to uncertainties related to genomic information?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147034/1/jgc40193.pd

Erratum to: How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147141/1/jgc40372.pd

CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α

Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle-drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared to standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demonstrated that the addition of CRLX101 to standard chemoradiotherapy significantly increased therapeutic efficacy by inhibiting DNA repair and HIF-1α pathway activation in tumor cells. Notably, CRLX101 was more effective than oxaliplatin at enhancing the efficacy of chemoradiotherapy, with CRLX101 and 5-fluorouracil (5-FU) producing the highest therapeutic efficacy. Gastrointestinal toxicity was also significantly lower for CRLX101 compared to CPT when combined with radiotherapy. Our results offer a preclinical proof of concept for CRLX101 as a modality to improve the outcome of neoadjuvant chemoradiotherapy for rectal cancer treatment, in support of ongoing clinical evaluation of this agent (LCC1315 {"type":"clinical-trial","attrs":{"text":"NCT02010567","term_id":"NCT02010567"}}NCT02010567)

SOX9 Maintains Reserve Stem Cells and Preserves Radioresistance in Mouse Small Intestine

Reserve intestinal stem cells (rISCs) are quiescent/slowly cycling under homeostatic conditions, allowing for their identification with label-retention assays. rISCs mediate epithelial regeneration after tissue damage by converting to actively proliferating stem cells (aISCs) that self renew and demonstrate multipotency, which are defining properties of stem cells. Little is known about the genetic mechanisms that regulate the production and maintenance of rISCs. High expression levels of the transcription factor Sox9 (Sox9high) are associated with rISCs. This study investigates the role of SOX9 in regulating the rISC state

Blithewold Mansion: A Vision for the Visitors Center

The Visitor Center is one of the most important programmatic elements of the estate. The building tends to get overlooked due to its small size and unclear signage. It currently houses a ticket booth, an information center and a gift shop, but there isn’t much space leftover for employees, guests or expansion

Spitzer mid-infrared spectroscopy of compact symmetric objects: What powers radio-loud active galactic nuclei?

We present low- and high-resolution mid-infrared (mid-IR) spectra and photometry for eight compact symmetric objects (CSOs) taken with the Infrared Spectrograph on the Spitzer Space Telescope. The hosts of these young, powerful radio galaxies show significant diversity in their mid-IR spectra. This includes multiple atomic fine-structure lines, H2 gas, polycyclic aromatic hydrocarbon (PAH) emission, warm dust from T = 50 to 150 K, and silicate features in both emission and absorption. There is no evidence in the mid-IR of a single template for CSO hosts, but 5/8 galaxies show similar moderate levels of star formation (<10 M_sun/yr from PAH emission) and silicate dust in a clumpy torus. The total amount of extinction ranges from A_V ~ 10 to 30, and the high-ionization [Ne V] 14.3 and 24.3 um transitions are not detected for any galaxy in the sample. Almost all CSOs show contributions both from star formation and active galactic nuclei (AGNs), suggesting that they occupy a continuum between pure starbursts and AGNs. This is consistent with the hypothesis that radio galaxies are created following a galactic merger; the timing of the radio activity onset means that contributions to the IR luminosity from both merger-induced star formation and the central AGN are likely. Bondi accretion is capable of powering the radio jets for almost all CSOs in the sample; the lack of [Ne V] emission suggests an advection-dominated accretion flow mode as a possible candidate. Merging black holes (BHs) with M_BH > 10^8 M_sun likely exist in all of the CSOs in the sample; however, there is no direct evidence from these data that BH spin energy is being tapped as an alternative mode for powering the radio jets.Comment: 22 pages, 14 figures; published in Ap

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Immunotherapy holds tremendous promise for improving cancer treatment1. Administering radiotherapy with immunotherapy has been shown to improve immune responses and can elicit an “abscopal effect”2. Unfortunately, response rates for this strategy remain low3. Herein, we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NPs formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent upon NP surface properties. We showed that AC-NPs deliver tumor specific proteins to antigen-presenting cells and significantly improve the efficacy of αPD-1 treatment using the B16F10 melanoma model, generating up to 20% cure rate as compared to 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+/Treg and CD8+/Treg ratios. Our work presents a novel strategy for improving cancer immunotherapy with nanotechnology