Democracy and Dysfunction: Rural Electric Cooperatives and the Surprising Persistence of the Separation of Ownership and Control

Since the 1930s, corporate law scholarship has focused narrowly on the public corporation and the problem of the separation of ownership and control-a problem many now believe has been mitigated or even solved. With rare exceptions, scholars have paid far less heed to other business forms that still play important roles in the American economy. In this Article, we examine a significant and almost completely overlooked business form, the Rural Electric Cooperative (REC). RECs were founded in a moment of optimism during the New Deal. As with other cooperatives, their organizational rules differed sharply from those of for-profit corporations. They were owned by their customers, with each customer-member having one vote irrespective of their energy consumption, and it was hoped these owners would provide active oversight of the REC\u27s managers and activities. Reality has proven otherwise. Corporate governance innovations of the last forty years have passed RECs by, leaving an organizational sector mired in governance dysfunctions stemming from the separation of ownership and control. Here we explain why RECs evolved as they did and why New Deal planners seized on the cooperative form to electrify the countryside; how significant governance problems have persisted, largely unaddressed, from the 1930s to today; and how a change in corporate governance rules, allowing for a market for corporate control in RECs, could fix some persistent problems in this still-important sector. Alternatively, we propose that RECs take up a new public role as rural broadband internet providers with a reinvigorated federal regulator to police governance failures

The Advanced Automated Directional Solidification Furnace

The Advanced Automated Directional Solidification Furnace (AADSF) is a five zone tubular furnace designed for Bridgman-Stockbarger, other techniques of crystal growth involving multiple temperature zones such as vapor transport experiments and other materials science experiments. The five zones are primarily designed to produce uniform hot and cold temperature regions separated by an adiabatic region constructed of a heat extraction plate and an insert to reduce radiation from the hot to the cold zone. The hot and cold zone temperatures are designed to reach 1600 C and 1100 C, respectively. AADSF operates on a Multi-Purpose Experiment Support Structure (MPESS) within the cargo bay of the Space Shuttle on the United States Microgravity Payload (USMP) missions. Two successful flights, both employing the directional solidification or Bridgman Stockbarger technique for crystal growth have been made, and crystals of HgCdTe and PbSnTe grown in microgravity have been produced on USMP-2 and USMP-3, respectively. The addition of a Sample Exchange Mechanism (SEM) will enable three different samples to be processed on future flights including the USMP-4 mission

Geometric origin of mechanical properties of granular materials

Some remarkable generic properties, related to isostaticity and potential energy minimization, of equilibrium configurations of assemblies of rigid, frictionless grains are studied. Isostaticity -the uniqueness of the forces, once the list of contacts is known- is established in a quite general context, and the important distinction between isostatic problems under given external loads and isostatic (rigid) structures is presented. Complete rigidity is only guaranteed, on stability grounds, in the case of spherical cohesionless grains. Otherwise, the network of contacts might deform elastically in response to load increments, even though grains are rigid. This sets an uuper bound on the contact coordination number. The approximation of small displacements (ASD) allows to draw analogies with other model systems studied in statistical mechanics, such as minimum paths on a lattice. It also entails the uniqueness of the equilibrium state (the list of contacts itself is geometrically determined) for cohesionless grains, and thus the absence of plastic dissipation. Plasticity and hysteresis are due to the lack of such uniqueness and may stem, apart from intergranular friction, from small, but finite, rearrangements, in which the system jumps between two distinct potential energy minima, or from bounded tensile contact forces. The response to load increments is discussed. On the basis of past numerical studies, we argue that, if the ASD is valid, the macroscopic displacement field is the solution to an elliptic boundary value problem (akin to the Stokes problem).Comment: RevTex, 40 pages, 26 figures. Close to published paper. Misprints and minor errors correcte

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Absolute Flux Density Calibration of the Greenland Telescope Data for Event Horizon Telescope Observations

Starting from the observing campaign in April 2018, the Greenland Telescope (GLT) has been added as a new station of the Event Horizon Telescope (EHT) array. Visibilities on baselines to the GLT, particularly in the North-South direction, potentially provide valuable new constraints for the modeling and imaging of sources such as M87*. The GLT's location at high Northern latitudes adds unique challenges to its calibration strategies. Additionally, the performance of the GLT was not optimal during the 2018 observations due to it being only partially commissioned at the time. This document describes the steps taken to estimate the various parameters (and their uncertainties) required for the absolute flux calibration of the GLT data as part of the EHT. In particular, we consider the non-optimized status of the GLT in 2018, as well as its improved performance during the 2021 EHT campaign.Comment: 17 pages, 4 figures, EHT Memo Series 2023-L1-0

Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics

<p>Abstract</p> <p>Background</p> <p>Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFβ has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT.</p> <p>Methods</p> <p>Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. <it>In vivo </it>tumor assay was performed to investigate the role of Snail1 in tumor initiation.</p> <p>Conclusion</p> <p>TGFβ induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of <it>Snail1 </it>in mesenchymal cells results in decreased <it>Nanog </it>promoter luciferase activity and loss of self-renewal characteristics <it>in vitro</it>. These changes confirm the direct role of Snail1 in some TISC traits. <it>In vivo</it>, the down-regulation of <it>Snail1 </it>reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFβ induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates <it>Nanog </it>expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation.</p

Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study

Epigenetic alterations measured in blood may help guide breast cancer treatment. The multisite prospective study TBCRC 005 was conducted to examine the ability of a novel panel of cell-free DNA methylation markers to predict survival outcomes in metastatic breast cancer (MBC) using a new quantitative multiplex assay (cMethDNA)

Drug-Tolerant Cancer Cells Show Reduced Tumor-Initiating Capacity: Depletion of CD44+ Cells and Evidence for Epigenetic Mechanisms

Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44+ cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration, whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many “stemness” genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44+ tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms

Prostate Cancer Cell Lines under Hypoxia Exhibit Greater Stem-Like Properties

Hypoxia is an important environmental change in many cancers. Hypoxic niches can be occupied by cancer stem/progenitor-like cells that are associated with tumor progression and resistance to radiotherapy and chemotherapy. However, it has not yet been fully elucidated how hypoxia influences the stem-like properties of prostate cancer cells. In this report, we investigated the effects of hypoxia on human prostate cancer cell lines, PC-3 and DU145. In comparison to normoxia (20% O2), 7% O2 induced higher expressions of HIF-1α and HIF-2α, which were associated with upregulation of Oct3/4 and Nanog; 1% O2 induced even greater levels of these factors. The upregulated NANOG mRNA expression in hypoxia was confirmed to be predominantly retrogene NANOGP8. Similar growth rates were observed for cells cultivated under hypoxic and normoxic conditions for 48 hours; however, the colony formation assay revealed that 48 hours of hypoxic pretreatment resulted in the formation of more colonies. Treatment with 1% O2 also extended the G0/G1 stage, resulting in more side population cells, and induced CD44 and ABCG2 expressions. Hypoxia also increased the number of cells positive for ABCG2 expression, which were predominantly found to be CD44bright cells. Correspondingly, the sorted CD44bright cells expressed higher levels of ABCG2, Oct3/4, and Nanog than CD44dim cells, and hypoxic pretreatment significantly increased the expressions of these factors. CD44bright cells under normoxia formed significantly more colonies and spheres compared with the CD44dim cells, and hypoxic pretreatment even increased this effect. Our data indicate that prostate cancer cells under hypoxia possess greater stem-like properties

Universal WBC reduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75583/1/j.1537-2995.2000.40060751.x.pd