American Indian Sacred Religious Sites and Government Development: A Conventional Analysis in an Unconventional Setting

For centuries, American Indians have regarded specific lands as essential to their livelihood, government, culture, and religion. Congress and the courts have at times recognized the important relationship between tribes and their lands. Recognition has not always coincided with protection; during the nineteenth century and part of the twentieth century a series of governmental actions resulted in the tribes surrendering title and possession to many of their ancestral lands. Recently, however, American Indians have become increasingly active litigants in a variety of contexts. In one set of cases, Indians challenged government development projects on public lands, contending that because the projects interfered with Indian sacred sites, they violated the free exercise clause. This Note focuses on the sacred lands cases and argues that courts have improperly transferred conventional free exercise analysis to an unfamiliar setting. As a result, these decisions fail to give adequate consideration to sincere Indian religious interests, and seem to conflict frequently with vital principles underlying the free exercise clause. Part I outlines the development of the Supreme Court\u27s current tripartite approach to free exercise issues. Part II examines the application of this approach to a series of earlier cases in which Indian free exercise claims did not involve sacred sites. Part III analyzes the sacred lands cases and concludes that they are inconsistent with both mainstream free exercise cases and the earlier Indian religious cases. After surveying possible legislative alternatives, Part IV offers recommendations for restructuring current free exercise analysis so that it leads to fairer evaluation of sacred site issues

Multicomponent metal-organic framework membranes for advanced functional composites.

The diverse chemical and structural properties of metal-organic frameworks (MOFs) make them attractive for myriad applications, but their native powder form is limiting for industrial implementation. Composite materials of MOFs hold promise as a means of exploiting MOF properties in engineered forms for real-world applications. While interest in MOF composites is growing, research to date has largely focused on utilization of single MOF systems. The vast number of different MOF structures provides ample opportunity to mix and match distinct MOF species in a single composite to prepare multifunctional systems. In this work, we describe the preparation of three types of multi-MOF composites with poly(vinylidene fluoride) (PVDF): (1) co-cast MOF MMMs, (2) mixed MOF MMMs, and (3) multilayer MOF MMMs. Finally, MOF MMMs are explored as catalytic membrane reactors for chemical transformations

Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in Geriatric Patients Under Anesthesia?

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring

Outcome Prediction for Unipolar Depression

Although effective drug and non-drug treatment for unipolar depressive illness exist, different individuals respond differently to different treatments. It is not uncommon for a given patient to lw switched several times from one treatment to another until an effective remedy for that particular patient is found. This process is costly in terms of time, money and suffering. It is thus desirable to determine at the outset the likdy response of a patient to the available treatments, so that the optimal one can be selected. Although prior attempts at outcome prediction with linear regression models have failed, recent work on this problem has indicated that the nonlinear predictive techniques of backpropagation and quadratic regression call account for a significant proportion of the variance in the data. The present research applies the nonlinear predictive technique of kernel regression to this problcrn, and employs cross-validation to test the ability of the resulting model to extract, from extremely noisy dinical data, information with predictive value. The importance of comparison with a suitable null hypothesis is illustrated.Office of Naval Research (N00014-95-1-0409

The development and neural basis of referential gaze perception

Infants are sensitive to the referential information conveyed by others’ eye gaze, which could be one of the developmental foundations of theory of mind. To investigate the neural correlates of gaze–object relations, we recorded ERPs from adults and 9-month-old infants while they watched scenes containing gaze shifts either towards or away from the location of a preceding object. In adults, object-incongruent gaze shifts elicited enhanced ERP amplitudes over the occipito-temporal area (N330). In infants, a similar posterior ERP component (N290) was greater for object-incongruent gaze shifts, which suggests that by the age of 9 months infants encode referential information of gaze in a similar way to adults. In addition, in infants we observed an early frontal ERP component (anterior N200), which showed higher amplitude in response to the perception of object-congruent gaze shifts. This component may reflect fast-track processing of socially relevant information, such as the detection of communicative or informative situations, and could form a developmental foundation for attention sharing, social learning and theory of mind

On Toroidal Horizons in Binary Black Hole Inspirals

We examine the structure of the event horizon for numerical simulations of two black holes that begin in a quasicircular orbit, inspiral, and finally merge. We find that the spatial cross section of the merged event horizon has spherical topology (to the limit of our resolution), despite the expectation that generic binary black hole mergers in the absence of symmetries should result in an event horizon that briefly has a toroidal cross section. Using insight gained from our numerical simulations, we investigate how the choice of time slicing affects both the spatial cross section of the event horizon and the locus of points at which generators of the event horizon cross. To ensure the robustness of our conclusions, our results are checked at multiple numerical resolutions. 3D visualization data for these resolutions are available for public access online. We find that the structure of the horizon generators in our simulations is consistent with expectations, and the lack of toroidal horizons in our simulations is due to our choice of time slicing.Comment: Submitted to Phys. Rev.

Novel C-Terminal Hsp90 Inhibitor for Head and Neck Squamous Cell Cancer (HNSCC) with in vivo Efficacy and Improved Toxicity Profiles Compared with Standard Agents

The final publication is available at Springer via http://dx.doi.org/10.1245/s10434-011-1971-1.Background - Current therapies for HNSCC, especially platinum agents, are limited by their toxicities and drug resistance. This study evaluates a novel C-terminal Hsp90 inhibitor (CT-Hsp90-I) for efficacy and toxicity in vitro and in vivo in an orthotopic HNSCC model. Our hypothesis is that C-terminal inhibitors exhibit improved toxicity/efficacy profiles over standard therapies and may represent a novel group of anticancer agents. Methods - MDA-1986 HNSCC cells were treated with doses of 17-AAG or KU363 (a CT-Hsp90-I) and compared for antiproliferation by GLO-Titer and trypan blue exclusion and for apoptosis by PARP cleavage and caspase-3 inactivation by Western analysis. In vivo studies in Nu/Nu mice examined an orthotopic model of MDA-1986 cells followed by drug dosing intraperitoneally for a 21-day period (mg/kg/dose: cisplatin = 3.5, low-dose KU363 = 5, high-dose KU363 = 25, 17-AAG = 175). Tumor size, weight, and toxicity (body score) were measured 3×/week. Results - The IC50 levels for KU363 = 1.2–2 μM in MDA-1986. KU363 induces apoptosis at 1 μM with cleavage of PARP and inactivation of caspase-3 levels after 24 h. Client proteins Akt and Raf-1 were also downregulated at 1–3 μM of drug. In vivo, 100% of controls had progressive disease, while 100% of cisplatin animals showed some response, all with significant systemic toxicity. High-dose KU363 showed 88% of animals responding and low-dose KU363 showed 75% responding. KU363 animals showed significantly less toxicity (P < 0.01) than cisplatin or 17-AAG. Conclusion - This novel CT-Hsp90-I KU363 manifests potent anticancer activity against HNSCC, showing excellent in vivo efficacy and reduced toxicity compared with standard agents justifying future translational evaluation

A Novel Intralymphatic Nanocarrier-Delivery System for Cisplatin Therapy in Breast Cancer with Improved Tumor Efficacy and Lower Systemic Toxicity In Vivo

Background A lymphatically delivered nanoconjugate of cisplatin was evaluated in an orthotopic mouse model of locoregionally metastatic breast cancer (LABC) to determine if it can overcome some of the limitations of standard cisplatin therapy such as high systemic toxicity. Methods Human breast cancer cells (107 MDA-MB-468LN) were injected into the mammary fat pad of female nu/nu mice. Once tumor volume reached 50 mm3; intravenous cisplatin or subcutaneous hyaluronan-cisplatin [HA-cisplatin] nanoconjugate was given 1/week × 3 at 3.3 mg/kg (platinum basis). Results Nanoconjugates co-localized with the tumors after subcutaneous peritumoral injection and demonstrated improved efficacy to intravenous cisplatin. After one month, renal tubular hemorrhage and edema were more prevalent in the intravenous formulation compared to subcutaneous HA-cisplatin nanoconjugates. Conclusions This nanocarrier delivery platform focuses drug in the areas where tumor burden is greatest, potentially reducing systemic toxicity, and has future applicability as a neoadjuvant or adjuvant therapy for LABC