Cultural Resources Investigations for the Oncor Permian Basin – Culberson 138 kV Transmission Line Project, Culberson, Reeves, and Ward Counties, Texas

URS Corporation (URS) was retained by Oncor Electric Delivery Company, LLC (Oncor) to conduct an intensive cultural resources survey of the new Permian Basin - Culberson 138 kilovolt (kV) Double-Circuit Transmission Line Project (Project) right-of-way (ROW) located in Culberson, Reeves, and Ward Counties, Texas. The proposed 70-foot (ft) (21-meter [m]) wide Project ROW encompasses approximately 825 acres and traverses a total of approximately 97 miles of rural lands between the existing Oncor Permian Basin Switching Station, located approximately four miles west of Monahans, Texas in Ward County, to the existing Oncor Culberson Switching Station, located approximately 17 miles south of the Texas/New Mexico state line in Culberson County. This includes 88.7 miles of the original route, along with 8.3 miles of additional segments that were evaluated. Currently, the Project is not subject to federal funding or permitting; therefore, no review under Section 106 of the National Historic Preservation Act of 1966, as amended, is required. Should the Project subsequently become subject to federal funding or permitting, the cultural resources investigations and site evaluations reported herein will be updated and coordinated with the Texas Historical Commission (THC) as part of fulfilling any Section 106 requirements that may arise at a later date. While the majority of the Project is located on private land, an approximately 6-mile long segment of the Project ROW traverses lands owned by University Lands (UL), which is a political subdivision of the State of Texas. Consequently, this portion of the project falls within the purview of the Antiquities Code of Texas, which requires the THC to review actions that have the potential to disturb prehistoric or historic sites in the public domain. In order to comply with the Antiquities Code, Antiquities Permit No. 7848 was obtained from the THC for the UL-owned lands, and the survey methods for this portion of the Project followed the THC’s archaeological survey standards for Texas. For the remaining areas of the Project, all cultural resources investigations were carried out in conformance with the methodologies outlined in the THC-approved Generic Research Design for Archaeological Surveys of Oncor Electric Delivery Electric Transmission Line Projects in Texas (PBS&J 2008). The cultural resources survey was conducted between December 7, 2015 and May 5, 2016, and consisted of an intensive 100 percent pedestrian survey and shovel testing within the Project ROW. The survey resulted in the identification of 16 newly-recorded sites and one previously recorded site (41WR85). Site forms were completed for each of the 16 newly identified archaeological sites, and trinomials were obtained from the Texas Archeological Research Laboratory. In addition, 16 isolated finds (IFs) were identified; however no site forms were prepared for IFs. All sites within the Project ROW were located in areas of eroded and/or mixed soils, lacked diagnostic artifacts, and were found to exhibit poor integrity context due to prior disturbances. Based on these observations, the portions of these sites within the Project ROW do not meet National Register of Historic Places (NRHP) and State Antiquities Landmark (SAL) eligibility requirements. However, because each of these sites appears to extend beyond the current Project ROW boundary, they have not been evaluated in their entirety and their overall NRHP and SAL eligibility is recommended to be Undetermined. Due to a lack of research potential and integrity, all IFs are recommended as not eligible for NRHP or SAL designation. During the survey, a small bedrock cavity was observed at site 41CU835. Due to safety concerns about the surrounding ground stability, this feature could not be fully investigated. The ground immediate adjacent to the cavity, as well as the upper two feet of the cavity, did not present any indications that it was culturally related, or that the cavity extended much deeper. The entirety of the observed cavity appeared to be too narrow to have served as an effective place of interment. However, based on survey level data, the cultural utilization of this feature could not be entirely ruled out. It was recommended that construction activities avoid this cavity and that site monitoring during construction be conducted, until such time as any cultural association is definitively ruled out, or until it can be confirmed that no construction impacts to the cavity would take place. A geomorphological assessment revealed that selected areas within the Project ROW potentially exhibit the necessary pedologic and geomorphic conditions for the deep burial and preservation of cultural deposits. These areas represent a combined total of 15.5 linear miles (25 kilometers) of Project ROW. In accordance with the Generic Research Design, monitoring was recommended for any transmission pole excavations in the areas that were assessed as exhibiting high geoarchaeological potential. An interim draft report of the foregoing recommendations was submitted to the THC on April 27, 2017. On May 26, 2017, the THC concurred with all interim report recommendations. During preparations for the monitoring effort, URS was notified by Oncor that a majority of the Project had already been constructed, including those areas recommended for monitoring. The only location that had not yet been constructed was the bedrock cavity at site 41CU835. On May 24, 2017, a meeting between Oncor, URS, and the THC resulted in an agreement that monitoring should be undertaken during construction activities near the bedrock cavity at site 41CU835. In addition, it was agreed that spot-checks would be performed within a subset of the previously constructed structures within high geoarchaeological probability areas, including portions of the Project owned by UL. Following completion of these tasks, it was agreed that a comprehensive revised draft report of investigations and findings (current report) would be submitted to the THC for review and project closure. Subsequent investigations at the bedrock cavity at 41CU835 were carried out from July 10-11, 2017. During the site visit, it was established that the cavity is located approximately 30 m to the southeast of the proposed location of monopole structure No. 56/3. Following additional inspections, it was possible to rule out any prehistoric use of this natural feature. The immediate area around the cavity was taped off for safety reasons so that other related construction activities would not adversely impact the cavity or surrounding area. On July 11, 2017, monitoring was carried out for the excavation of monopole structure no. 56/3. Soil stratigraphy was recorded for the total depth of the excavation, which was 20 ft. No cultural materials were identified From August 12-13, 2017, URS archaeologists performed spot-checks for 99 monopoles, including 53 structures within the Project ROW extending approximately 10 kilometers (km) west of the Pecos River in Reeves County; 22 structures within the Project ROW extending approximately 4 km east of the Pecos River in Ward County; and 24 structures within the Project ROW extending approximately 4.5 km across Monument Draw within UL in Ward County. Spot-checking included visual inspection and photo documentation of disturbances, as well as ground surface inspection to identify cultural resources. The Project ROW around each monopole exhibited construction related disturbances from equipment access roads and from drilling operations. No evidence was found that indicated any deeply buried cultural resource sites were impacted from auguring. Within the intervening areas between monopoles, however, a total of two previously unrecorded, low-density historic surface scatters (41RV128 and 41RV129) and three new IFs (H-07, H08, and P-28) were identified and recorded. Both sites were found to exhibit poor integrity due to prior disturbances, and low research potential due to minimal information potential. The portions of these sites within the Project ROW were not found to meet NRHP and SAL eligibility requirements. However, because each of these sites appears to extend beyond of the current Project ROW boundary, they have not been evaluated in their entirety and their overall NRHP and SAL eligibility is recommended to be Undetermined. The three new IFs are recommended as not eligible for NRHP or SAL designation. Based on the final results of the survey, monitoring, and spot-checking investigations, no cultural resources sites eligible for listing in the NRHP or that merit SAL designation within the Project ROW will be affected by the Project, and it is recommended that the project be allowed to proceed. Should the dimensions of the Project ROW change, additional archaeological investigations may be warranted. Should any unmarked prehistoric or historic human remains or burials be encountered at any point during the project, the area of the remains is considered a cemetery under current Texas law. All cemeteries are protected under State law and cannot be disturbed. Section 28.03(f) of the Texas Penal Code provides that intentional damage or destruction inflicted on a human burial site is a state jail felony. If a cemetery is identified in the Project ROW, all work in the immediate area of the discovery must cease and the THC must be notified by contacting the History Programs Division at (512) 463-5853 and the Archeology Division at (512) 463-6096. Following consultation with the THC, a treatment or avoidance plan would be developed and implemented. No artifacts were collected during the survey. Pursuant to 13 TAC 26.17, correspondence, field records, and photographs generated during field investigations have been prepared for permanent curation at the Texas Archeological Research Laboratory, Austin, Texas

Endothelial colony-forming cells ameliorate endothelial dysfunction via secreted factors following ischemia-reperfusion injury

Damage to endothelial cells contributes to acute kidney injury (AKI) by leading to impaired perfusion. Endothelial colony-forming cells (ECFC) are endothelial precursor cells with high proliferative capacity, pro-angiogenic activity, and in vivo vessel forming potential. We hypothesized that ECFC may ameliorate the degree of AKI and/or promote repair of the renal vasculature following ischemia-reperfusion (I/R). Rat pulmonary microvascular endothelial cells (PMVEC) with high proliferative potential were compared with pulmonary artery endothelial cells (PAEC) with low proliferative potential in rats subjected to renal I/R. PMVEC administration reduced renal injury and hastened recovery as indicated by serum creatinine and tubular injury scores, while PAEC did not. Vehicle-treated control animals showed consistent reductions in renal medullary blood flow (MBF) within 2 h of reperfusion, while PMVEC protected against loss in MBF as measured by laser Doppler. Interestingly, PMVEC mediated protection occurred in the absence of homing to the kidney. Conditioned medium (CM) from human cultured cord blood ECFC also conveyed beneficial effects against I/R injury and loss of MBF. Moreover, ECFC-CM significantly reduced the expression of ICAM-1 and decreased the number of differentiated lymphocytes typically recruited into the kidney following renal ischemia. Taken together, these data suggest that ECFC secrete factors that preserve renal function post ischemia, in part, by preserving microvascular function

Functional B-1 progenitor cells are present in the hematopoietic stem cell-deficient embryo and depend on Cbfβ for their development

The fetal liver is a major hematopoietic site containing progenitor cells that give rise to nearly all blood cells, including B-1 cells. Because the fetal liver is not a de novo site of hematopoietic stem cell (HSC) or progenitor-cell emergence, it must be seeded by yolk sac (YS)-derived erythromyeloid progenitors at embryonic day (E) 8.5-E10 and aorta-gonado-mesonephros (AGM)-derived HSCs at E10.5-E11.5. Although the B-1 progenitor cell pool in the fetal liver is considered to be of HSC origin, we have previously proposed that YS-derived B-1 progenitors may also contribute to this pool. Until now, it has been impossible to determine whether HSC-independent B-1 progenitor cells exist in the fetal liver. Here, we demonstrate the presence of transplantable fetal-liver B-1 and marginal zone B progenitor cells in genetically engineered HSC-deficient embryos. HSC-deficient YS and AGM tissues produce B-1 progenitors in vitro and thus may serve as sites of origin for the B-1 progenitors that seed the fetal liver. Furthermore, we have found that core-binding factor beta (Cbfβ) expression is required for fetal-liver B-1 progenitor cell maturation and expansion. Our data provide, to our knowledge, the first evidence for the presence of B-1 progenitor cells in the fetal liver that arise independently of HSCs and implicate Cbfβ as a critical molecule in the development of this lineage

The feasibility of online video calling to engage patients with cystic fibrosis in exercise training.

Introduction Physical activity, including structured exercise, is an essential component in the management of cystic fibrosis. The use of telehealth such as video-calling may be a useful method for the delivery of exercise and physical activity interventions, though the feasibility of this remains unknown. Methods Nine patients with cystic fibrosis (three female, six male, 30.9 ± 8.7 years) volunteered to participate. Participants completed an eight-week exercise training intervention conducted via Skype, using personalised exercises, with all sessions supervised by an exercise therapist. Feasibility was assessed by demand, implementation, practicality and acceptability. Changes in anthropometric, pulmonary, physical activity and quality of life variables were also assessed. Results Two male participants withdrew from the study, citing lack of available time. The remaining participants found use of Skype useful, with a mean satisfaction rating of 9/10, and three participants requesting to continue the sessions beyond the duration of the study. Mean compliance with sessions was 68%, with mean duration of sessions being 20 min. A total of 25% of calls suffered from technical issues such as video or audio lags. Anthropometric, pulmonary, physical activity and quality of life variables remained unchanged over the course of the study period. Discussion The use of Skype to deliver an exercise intervention to patients withcystic fibrosis was found to be technologically feasible, and acceptable among participants. Findings have implications for clinical practice and could allow care teams to engage patients remotely in exercise. Further research is required to assess the efficacy of this modality on increasing physical activity and associated health outcomes

Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence

Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans

Functional analysis of transcription factor binding sites in human promoters

BACKGROUND: The binding of transcription factors to specific locations in the genome is integral to the orchestration of transcriptional regulation in cells. To characterize transcription factor binding site function on a large scale, we predicted and mutagenized 455 binding sites in human promoters. We carried out functional tests on these sites in four different immortalized human cell lines using transient transfections with a luciferase reporter assay, primarily for the transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1. RESULTS: In each cell line, between 36% and 49% of binding sites made a functional contribution to the promoter activity; the overall rate for observing function in any of the cell lines was 70%. Transcription factor binding resulted in transcriptional repression in more than a third of functional sites. When compared with predicted binding sites whose function was not experimentally verified, the functional binding sites had higher conservation and were located closer to transcriptional start sites (TSSs). Among functional sites, repressive sites tended to be located further from TSSs than were activating sites. Our data provide significant insight into the functional characteristics of YY1 binding sites, most notably the detection of distinct activating and repressing classes of YY1 binding sites. Repressing sites were located closer to, and often overlapped with, translational start sites and presented a distinctive variation on the canonical YY1 binding motif. CONCLUSIONS: The genomic properties that we found to associate with functional TF binding sites on promoters -- conservation, TSS proximity, motifs and their variations -- point the way to improved accuracy in future TFBS predictions

A Hydrogen-Sulfide Derivative of Mesalamine Reduces the Severity of Intestinal and Lung Injury in Necrotizing Enterocolitis Through Endothelial Nitric Oxide Synthase

Necrotizing enterocolitis (NEC) remains a devastating disease that affects preterm infants. Hydrogen sulfide (H2S) donors have been shown to reduce the severity of NEC, but the optimal compound has yet to be identified. We hypothesized that oral H2S-Mesalamine (ATB-429) would improve outcomes in experimental NEC, and its benefits would be dependent on endothelial nitric oxide synthase (eNOS) pathways. NEC was induced in 5-day-old wild-type (WT) and eNOS knockout (eNOSKO) pups by formula feeding and stress. Four groups were studied in both WT and eNOSKO mice: 1) breastfed controls, 2) NEC, 3) NEC + 50 mg/kg mesalamine, and 4) NEC + 130 mg/kg ATB-429. Mesalamine and ATB-429 doses were equimolar. Pups were monitored for sickness scores and perfusion to the gut was measured by Laser Doppler Imaging (LDI). After euthanasia of the pups, intestine and lung were hematoxylin and eosin-stained and scored for injury in a blind fashion. TLR4 expression was quantified by Western blot and IL-6 expression by ELISA. P \u3c 0.05 was significant. Both WT and eNOSKO breastfed controls underwent normal development and demonstrated milder intestinal and pulmonary injury compared with NEC groups. For the WT groups, ATB-429 significantly improved weight gain, reduced clinical sickness score, and improved perfusion compared with the NEC group. In addition, WT ATB-429 pups had a significantly milder intestinal and pulmonary histologic injury when compared with NEC. ATB-429 attenuated the increase in TLR4 and IL-6 expression in the intestine. When the experiment was repeated in eNOSKO pups, ATB-429 offered no benefit in weight gain, sickness scores, perfusion, intestinal injury, pulmonary injury, or decreasing intestinal inflammatory markers. An H2S derivative of mesalamine improves outcomes in experimental NEC. Protective effects appear to be mediated through eNOS. Further research is warranted to explore whether ATB-429 may be an effective oral therapy to combat NEC

Angiogenesis: A Cellular Response to Traumatic Injury

The development of new vasculature plays a significant role in a number of chronic disease states, including neoplasm growth, peripheral arterial disease, and coronary artery disease, among many others. Traumatic injury and hemorrhage, however, is an immediate, often dramatic pathophysiologic insult which can also necessitate neovascularization to promote healing. Traditional understanding of angiogenesis involved resident endothelial cells branching outward from localized niches in the periphery. Additionally, there are a small number of circulating endothelial progenitor cells which participate directly in the process of neovessel formation. The bone marrow stores a relatively small number of so-called pro-angiogenic hematopoietic progenitor cells (PACs) – that is, progenitor cells of a hematopoietic potential that differentiate into key structural cells and stimulate or otherwise support local cell growth/differentiation at the site of angiogenesis. Following injury, a number of cytokines and intercellular processes are activated or modulated to promote development of new vasculature. These processes initiate and maintain a robust response to vascular insult, allowing new vessels to canalize and anastomose and provide timely oxygen delivering to healing tissue. Ultimately as we better understand the key players in the process of angiogenesis we can look to develop novel techniques to promote healing following injury

Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia

Background: Interleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury. Methods: Adult male C57Bl6J mice were anesthetized, and a laparotomy was performed. Baseline intestinal perfusion was assessed by laser Doppler imaging. Intestinal ischemia was induced for 60 min by temporarily occluding the superior mesenteric artery. After ischemia, treatments were administered intraperitoneally before closure (Vehicle: 250 μL phosphate-buffered-saline, IL6 low dose (20 ng), IL6 medium dose (200 ng), or IL6 high dose (2 μg)). Animals were allowed to recover for 24 h, were reanesthetized, and their mesenteric perfusion was reassessed. Perfusion was expressed as percentage of baseline. Animals were then sacrificed, and the intestines were explanted for histological analysis. Separate frozen samples were homogenized and analyzed by ELISA for vascular endothelial growth factor (VEGF) and interferon gamma-induced protein 10. Results: IL6 increased mesenteric perfusion in low dose groups only, whereas it improved postischemic mucosal injury scores in both low and medium dose groups. No differences in perfusion or histology were seen when high dose IL6 was utilized. Intestinal VEGF was higher in the low dose IL6 group compared to vehicle, whereas IP-10 levels were lower in low and medium dose groups compared to vehicle. No differences were noted compared to vehicle in intestinal VEGF and IP-10 with high dose IL6 therapy

Mll1 is essential for the senescenceassociated secretory phenotype

Oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), while tumor-suppressive, also promote procarcinogenic effects by activating the DNA damage response (DDR), which in turn induces inflammation. This inflammatory response prominently includes an array of cytokines known as the senescence-associated secretory phenotype (SASP). Previous observations link the transcription-associated methyltransferase and oncoprotein MLL1 to the DDR, leading us to investigate the role of MLL1 in SASP expression. Our findings reveal direct MLL1 epigenetic control over proproliferative cell cycle genes: MLL1 inhibition represses expression of proproliferative cell cycle regulators required for DNA replication and DDR activation, thus disabling SASP expression. Strikingly, however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation. More broadly, MLL1 inhibition also reduces “SASP-like” inflammatory gene expression from cancer cells in vitro and in vivo independently of senescence. Taken together, these data demonstrate that MLL1 inhibition may be a powerful and effective strategy for inducing cancerous growth arrest through the direct epigenetic regulation of proliferation-promoting genes and the avoidance of deleterious OIS- or TIS-related tumor secretomes, which can promote both drug resistance and tumor progression