Rock and a hard place, A: exploring Fremont territoriality through the pinnacle architecture of Douglas Creek, Rio Blanco County, Colorado

2022 Summer.Includes bibliographical references.Fremont occupations in northwestern Colorado's Douglas Creek have long captured the attention of travelers and archaeologists. Spanish explorers in the 18th century dubbed its canyon corridor "El Cañon Pintado", due to the impressive rock art peppered throughout. Researchers in the 20th century were captivated by the masonry architecture perched on pinnacle landforms in the area and some wagered that they may have served defensive purposes. This was a warranted premise, considering the known territorial tendencies of Fremont peoples in the Uinta Basin, and the social and environmental changes that occurred around the time of the pinnacle occupations from 1000–1550 CE. This thesis represents the first synthetic study of seven pinnacle structures in Douglas Creek and undertakes to determine whether they were indeed defensive in nature through three research themes. Examined first are the physical conditions associated with the pinnacle sites and finds that they are in naturally defensible settings, such as inconspicuous locations on the landscape and areas with steep slopes, dangerous cliffs, and protective blinds. Architectural components of the structures are then assessed to understand how much planning and effort went into their construction. The results show that the masonry construction attests to attention and care on behalf of the architects, although the structures are not always so meticulously built, perhaps signaling a lack of resources on their part. Finally, viewsheds of each pinnacle site are analyzed, and the results reveal that they provide commanding views of the canyon corridor, arable land, and some storage granaries (another form of masonry architecture attributed to the Fremont). These results suggest that the Douglas Creek Fremont were engaged in a mostly passive form of defensibility but retained the option to actively engage in conflicts. This thesis offers these foregoing insights about the territorial postures assumed by Douglas Creek Fremont during a time of socioeconomic stress stemming from drought, demographic shifts, and increased regional conflicts

Lepton Jets in (Supersymmetric) Electroweak Processes

We consider some of the recent proposals in which weak-scale dark matter is accompanied by a GeV scale dark sector that could produce spectacular lepton-rich events at the LHC. Since much of the collider phenomenology is only weakly model dependent it is possible to arrive at generic predictions for the discovery potential of future experimental searches. We concentrate on the production of dark states through $Z^0$ bosons and electroweak-inos at the Tevatron or LHC, which are the cleanest channels for probing the dark sector. We properly take into account the effects of dark radiation and dark cascades on the formation of lepton jets. Finally, we present a concrete definition of a lepton jet and suggest several approaches for inclusive experimental searches.Comment: 23 pages, 13 figures, published version, added section 3.3 expanding on lepton jet's morpholog

An Early and Comprehensive Millimetre and Centimetre Wave and X-ray Study of SN 2011dh: a Non-Equipartition Blast Wave Expanding into a Massive Stellar Wind

Only a handful of supernovae (SNe) have been studied in multiwavelengths from the radio to X-rays, starting a few days after the explosion. The early detection and classification of the nearby Type IIb SN 2011dh/PTF 11eon in M51 provides a unique opportunity to conduct such observations. We present detailed data obtained at one of the youngest phase ever of a core-collapse SN (days 3–12 after the explosion) in the radio, millimetre and X-rays; when combined with optical data, this allows us to explore the early evolution of the SN blast wave and its surroundings. Our analysis shows that the expanding SN shock wave does not exhibit equipartition (ϵe/ϵB ∼ 1000), and is expanding into circumstellar material that is consistent with a density profile falling like R−2. Within modelling uncertainties we find an average velocity of the fast parts of the ejecta of 15 000 ± 1800 km s−1, contrary to previous analysis. This velocity places SN 2011dh in an intermediate blast wave regime between the previously defined compact and extended SN Type IIb subtypes. Our results highlight the importance of early (∼1 d) high-frequency observations of future events. Moreover, we show the importance of combined radio/X-ray observations for determining the microphysics ratio ϵe/ϵB

Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma

Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM

Functional network disorganization and cognitive decline following fractionated whole-brain radiation in mice

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain\u27s functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of temporally evolving neural dynamics as they relate to cerebral hemodynamics for bridging with human studies. In order to adequately study the underlying mechanisms of RT-induced cognitive dysfunction, the development of clinically mimetic RT protocols in animal models is needed. To address these challenges, we developed a fractionated whole-brain RT protocol (3Gy/day for 10 days) and applied longitudinal wide field optical imaging (WFOI) of neural and hemodynamic brain activity at 1, 2, and 3 months post RT. At each time point, mice were subject to repeated behavioral testing across a variety of sensorimotor and cognitive domains. Disruptions in cortical neuronal and hemodynamic activity observed 1 month post RT were significantly worsened by 3 months. While broad changes were observed in functional brain organization post RT, brain regions most impacted by RT occurred within those overlapping with the mouse default mode network and other association areas similar to prior reports in human subjects. Further, significant cognitive deficits were observed following tests of novel object investigation and responses to auditory and contextual cues after fear conditioning. Our results fill a much-needed gap in understanding the effects of whole-brain RT on systems level brain organization and how RT affects neuronal versus hemodynamic signaling in the cortex. Having established a clinically-relevant injury model, future studies can examine therapeutic interventions designed to reduce neuroinflammation-based injury following RT. Given the overlap of sequelae that occur following RT with and without chemotherapy, these tools can also be easily incorporated to examine chemotherapy-related cognitive impairment

Debiasing the NEOWISE Cryogenic Mission Comet Populations

We use NEOWISE data from the four-band and three-band cryogenic phases of the Wide-field Infrared Survey Explorer mission to constrain size distributions of the comet populations and debias measurements of the short- and long-period comet (LPC) populations. We find that the fit to the debiased LPC population yields a cumulative size−frequency distribution (SFD) power-law slope (β) of −1.0 ± 0.1, while the debiased Jupiter-family comet (JFC) SFD has a steeper slope with β = −2.3 ± 0.2. The JFCs in our debiased sample yielded a mean nucleus size of 1.3 km in diameter, while the LPCs' mean size is roughly twice as large, 2.1 km, yielding mean size ratios (〈D_(LPC)〉/〈D_(JFC)〉) that differ by a factor of 1.6. Over the course of the 8 months of the survey, our results indicate that the number of LPCs passing within 1.5 au are a factor of several higher than previous estimates, while JFCs are within the previous range of estimates of a few thousand down to sizes near 1.3 km in diameter. Finally, we also observe evidence for structure in the orbital distribution of LPCs, with an overdensity of comets clustered near 110° inclination and perihelion near 2.9 au that is not attributable to observational bias

An Early & Comprehensive Millimeter and Centimeter Wave and X-ray Study of Supernova 2011dh: A Non-Equipartition Blastwave Expanding into A Massive Stellar Wind

Only a handful of supernovae (SNe) have been studied in multi-wavelength from radio to X-rays, starting a few days after explosion. The early detection and classification of the nearby type IIb SN2011dh/PTF11eon in M51 provides a unique opportunity to conduct such observations. We present detailed data obtained at the youngest phase ever of a core-collapse supernova (days 3 to 12 after explosion) in the radio, millimeter and X-rays; when combined with optical data, this allows us to explore the early evolution of the SN blast wave and its surroundings. Our analysis shows that the expanding supernova shockwave does not exhibit equipartition (e_e/e_B ~ 1000), and is expanding into circumstellar material that is consistent with a density profile falling like R^-2. Within modeling uncertainties we find an average velocity of the fast parts of the ejecta of 15,000 +/- 1800 km/s, contrary to previous analysis. This velocity places SN 2011dh in an intermediate blast-wave regime between the previously defined compact and extended SN IIb subtypes. Our results highlight the importance of early (~ 1 day) high-frequency observations of future events. Moreover, we show the importance of combined radio/X-ray observations for determining the microphysics ratio e_e/e_B.Comment: 9 pages, 5 figures, submitted to Ap

The Sloan Digital Sky Survey Quasar Catalog I. Early Data Release

We present the first edition of the Sloan Digital Sky Survey (SDSS) Quasar Catalog. The catalog consists of the 3814 objects (3000 discovered by the SDSS) in the initial SDSS public data release that have at least one emission line with a full width at half maximum larger than 1000 km/s, luminosities brighter than M_i^* = -23, and highly reliable redshifts. The area covered by the catalog is 494 square degrees; the majority of the objects were found in SDSS commissioning data using a multicolor selection technique. The quasar redshifts range from 0.15 to 5.03. For each object the catalog presents positions accurate to better than 0.2" rms per coordinate, five band (ugriz) CCD-based photometry with typical accuracy of 0.05 mag, radio and X-ray emission properties, and information on the morphology and selection method. Calibrated spectra of all objects in the catalog, covering the wavelength region 3800 to 9200 Angstroms at a spectral resolution of 1800-2100, are also available. Since the quasars were selected during the commissioning period, a time when the quasar selection algorithm was undergoing frequent revisions, the sample is not homogeneous and is not intended for statistical analysis.Comment: 27 pages, 4 figures, 4 tables, accepted by A

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): PartA = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W

Deep Underground Science and Engineering Laboratory - Preliminary Design Report

The DUSEL Project has produced the Preliminary Design of the Deep Underground Science and Engineering Laboratory (DUSEL) at the rehabilitated former Homestake mine in South Dakota. The Facility design calls for, on the surface, two new buildings - one a visitor and education center, the other an experiment assembly hall - and multiple repurposed existing buildings. To support underground research activities, the design includes two laboratory modules and additional spaces at a level 4,850 feet underground for physics, biology, engineering, and Earth science experiments. On the same level, the design includes a Department of Energy-shepherded Large Cavity supporting the Long Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates one laboratory module and additional spaces for physics and Earth science efforts. With input from some 25 science and engineering collaborations, the Project has designed critical experimental space and infrastructure needs, including space for a suite of multidisciplinary experiments in a laboratory whose projected life span is at least 30 years. From these experiments, a critical suite of experiments is outlined, whose construction will be funded along with the facility. The Facility design permits expansion and evolution, as may be driven by future science requirements, and enables participation by other agencies. The design leverages South Dakota's substantial investment in facility infrastructure, risk retirement, and operation of its Sanford Laboratory at Homestake. The Project is planning education and outreach programs, and has initiated efforts to establish regional partnerships with underserved populations - regional American Indian and rural populations