Significance Testing Of Archeological Sites 41SR242, The Cornelio Alvarez SR. Site, Starr County, Texas

The Texas Department of Transportation (TxDOT), conducted National Register of Historic Places (NRHP) eligibility testing of the Cornelio Alvarez Sr. site (41SR242) as part of the State Loop (SL) 195 project (Project) (CSJ: 3632-01-001) in Starr County, Texas. Subsequent to the field investigations, SWCA Environmental Consultants (SWCA) conducted artifact analysis, reporting, and curation preparation for the multi-component historic and prehistoric site. Investigations were conducted in compliance with Section 106 of the National Historic Preservation Act (54 United State Code 30601) and the Antiquities Code of Texas (9 Natural Resources Code). The investigations assessed the site’s eligibility for listing on the NRHP (36 Code of Federal Regulations 60.4) and for designation as a State Antiquities Landmark (SAL; 13 Texas Administrative Code 26.8, 26.12). Christopher W. Ringstaff served as Principal Investigator under Texas Antiquities Permit Number 7912. TxDOT conducted the field investigations were from February 20–24, 2017, and April 10–14, 2017. Site 41SR242 is primarily a Middle to Late Archaic site with lesser Late Prehistoric and perhaps earlier components. The open occupational site is located on an upland margin landform in a tributary valley a few miles from the Rio Grande. The investigations revealed material assemblages consisting of diffusely scattered burned rock, debitage, and lithic tools, which were predominantly recovered from a 30- to 50- cm-thick stratum of mixed artifacts. However, a few concentrations of artifacts were identified, and each location yielded isolated intact features. Formation and post-depositional processes are generally not conducive to preservation of intact archeological surfaces, patterns, or site structure. Although the overall site lacks integrity and potential data yield, isolated discrete behavioral loci are present. Therefore, site 41SR242 is recommended as eligible for the NRHP and as an SAL. This recommendation pertains to the portions of the site within the APE. The site extends beyond the APE, and the areas outside of the APE have not been evaluated

Significance Testing of Archeological Site 41SR242, The Cornelio Alvarez Sr. Site, Starr County, Texas

The Texas Department of Transportation (TxDOT), conducted National Register of Historic Places (NRHP) eligibility testing of the Cornelio Alvarez Sr. site (41SR242) as part of the State Loop (SL) 195 project (Project) (CSJ: 3632-01-001) in Starr County, Texas. Subsequent to the field investigations, SWCA Environmental Consultants (SWCA) conducted artifact analysis, reporting, and curation preparation for the multi-component historic and prehistoric site. Investigations were conducted in compliance with Section 106 of the National Historic Preservation Act (54 United State Code 30601) and the Antiquities Code of Texas (9 Natural Resources Code). The investigations assessed the site’s eligibility for listing on the NRHP (36 Code of Federal Regulations 60.4) and for designation as a State Antiquities Landmark (SAL; 13 Texas Administrative Code 26.8, 26.12). Christopher W. Ringstaff served as Principal Investigator under Texas Antiquities Permit Number 7912. TxDOT conducted the field investigations were from February 20–24, 2017, and April 10–14, 2017. Site 41SR242 is primarily a Middle to Late Archaic site with lesser Late Prehistoric and perhaps earlier components. The open occupational site is located on an upland margin landform in a tributary valley a few miles from the Rio Grande. The investigations revealed material assemblages consisting of diffusely scattered burned rock, debitage, and lithic tools, which were predominantly recovered from a 30- to 50-cm-thick stratum of mixed artifacts. However, a few concentrations of artifacts were identified, and each location yielded isolated intact features. Formation and post-depositional processes are generally not conducive to preservation of intact archeological surfaces, patterns, or site structure. Although the overall site lacks integrity and potential data yield, isolated discrete behavioral loci are present. Therefore, site 41SR242 is recommended as eligible for the NRHP and as an SAL. This recommendation pertains to the portions of the site within the APE. The site extends beyond the APE, and the areas outside of the APE have not been evaluated

Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans

Many animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of Caenorhabditis elegans for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference. Calcium imaging and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory sensory neurons into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.Organismic and Evolutionary BiologyPhysic

Chemical Tuning Enhances Both Potency Toward Nrf2 and In Vitro Therapeutic Index of Triterpenoids

The transcription factor Nrf2 protects against a number of experimental pathologies, and is a promising therapeutic target. The clinical investigation of a potent Nrf2-inducing agent, the triterpenoid (TP) bardoxolone methyl (BARD), was recently halted due to adverse cardiovascular events in chronic kidney disease patients, although the underlying mechanisms are yet to be resolved. The majority of small molecule Nrf2 inducers are electrophilic and trigger Nrf2 accumulation via the chemical modification of its redox-sensitive repressor Keap1. Therefore, it is pertinent to question whether the therapeutic targeting of Nrf2 could be hindered in many cases by the inherent reactivity of a small molecule inducer toward unintended cellular targets, a key mechanism of drug toxicity. Using H4IIE-ARE8L hepatoma cells, we have examined the relationship between (a) Nrf2 induction potency, (b) toxicity and (c) in vitro therapeutic index (ratio of b:a) for BARD and a number of other small molecule activators of Nrf2. We show that BARD exhibits the highest potency toward Nrf2 and the largest in vitro therapeutic index among compounds that have been investigated clinically (namely BARD, sulforaphane and dimethylfumarate). Through further examination of structurally related TPs, we demonstrate that an increase in potency toward Nrf2 is associated with a relatively smaller increase in toxicity, indicating that medicinal chemistry can be used to enhance the specificity of a compound as an inducer of Nrf2 signaling whilst simultaneously increasing its therapeutic index. These findings will inform the continuing design and development of drugs targeting Nrf

Chemical tuning enhances both potency toward Nrf2 and<em> in vitro</em> therapeutic index of triterpenoids

The transcription factor Nrf2 protects against a number of experimental pathologies, and is a promising therapeutic target. The clinical investigation of a potent Nrf2-inducing agent, the triterpenoid (TP) bardoxolone methyl (BARD), was recently halted due to adverse cardiovascular events in chronic kidney disease patients, although the underlying mechanisms are yet to be resolved. The majority of small molecule Nrf2 inducers are electrophilic and trigger Nrf2 accumulation via the chemical modification of its redox-sensitive repressor Keap1. Therefore, it is pertinent to question whether the therapeutic targeting of Nrf2 could be hindered in many cases by the inherent reactivity of a small molecule inducer toward unintended cellular targets, a key mechanism of drug toxicity. Using H4IIE-ARE8L hepatoma cells, we have examined the relationship between (a) Nrf2 induction potency, (b) toxicity and (c) in vitro therapeutic index (ratio of b:a) for BARD and a number of other small molecule activators of Nrf2. We show that BARD exhibits the highest potency toward Nrf2 and the largest in vitro therapeutic index among compounds that have been investigated clinically (namely BARD, sulforaphane and dimethylfumarate). Through further examination of structurally related TPs, we demonstrate that an increase in potency toward Nrf2 is associated with a relatively smaller increase in toxicity, indicating that medicinal chemistry can be used to enhance the specificity of a compound as an inducer of Nrf2 signaling whilst simultaneously increasing its therapeutic index. These findings will inform the continuing design and development of drugs targeting Nrf2.</p

Release characteristics of selected carbon nanotube polymer composites

Multi-walled carbon nanotubes (MWCNTs) are commonly used in polymer formulations to improve strength, conductivity, and other attributes. A developing concern is the potential for carbon nanotube polymer nanocomposites to release nanoparticles into the environment as the polymer matrix degrades or is mechanically stressed. Here, we review characteristics related to release potential of five sets of polymer systems: epoxy, polyamide, polyurethane, polyethylene, and polycarbonate. Our review includes consideration of general characteristics and use of the polymer (as related to potential MWCNT release) and its MWCNT composites; general potential for nanomaterial release (particularly MWCNTs) due to degradation and mechanical stresses during use; and potential effects of stabilizers and plasticizers on polymer degradation. We examine UV degradation, temperature extremes, acid-base catalysis, and stresses such as sanding. Based on a high-level summary of the characteristics considered, the potential for release of MWCNT with typical, intended consumer use is expected to be low. © 2013 Elsevier Ltd. All rights reserved

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

Potential of dynamic ocean management strategies for western Pacific leatherback sea turtle bycatch mitigation in New Zealand

Western Pacific leatherback sea turtles (Dermochelys coriacea) are a priority bycatch mitigation concern due to the projected extinction of the population before the end of the 21st century. The species regularly occurs as bycatch in gillnet and surface longline fisheries. Here, we explore the potential for dynamic ocean management in an emerging hotspot of leatherback sea turtle bycatch in the New Zealand pelagic longline fishery. We compared spatial areas of different sizes built from single oceanographic covariates as well as built from a composite risk surface developed through ensemble random forests. We found that, individually, the Okubo–Weiss parameter, sea surface temperature (SST) anomaly, SST, moon phase, and distance to the SST front were important oceanographic covariates for leatherback sea turtle bycatch. However, the spatial areas built from the composite risk surface were the most effective at discriminating sets with and without bycatch across a range of risk cutoffs. When we also considered implementation metrics of spatial area and coherence as part of performance, the area derived from the composite risk surface with a risk of interaction per set greater than 52% performed best. This spatial area was ephemeral, occurring 1 or 2 weeks each year, and localized, occurring along the north coast of East Cape in the North Island of New Zealand. The apparent presence of discrete spatial areas with elevated risk may be useful to inform future management in the area. Considering implementation metrics in defining utility was useful for identifying tradeoffs between the total size and the underlying covariates delineating a spatial area. As such, we recommend these types of metrics to be included when designing spatial bycatch mitigation strategies elsewhere

Massive Spin-2 States as the Origin of the Top Quark Forward-Backward Asymmetry

We show that the anomalously large top quark forward-backward asymmetry observed by CDF and D\O\, can naturally be accommodated in models with flavor-violating couplings of a new massive spin-2 state to quarks. Regardless of its origin, the lowest-order couplings of a spin-2 boson to fermions are analogous to the coupling of the graviton to energy/momentum, leading to strong sensitivity of the effects associated with its virtual exchange to the energy scales at hand. Precisely due to this fact, the observed dependence of the asymmetry on the $t\bar t$ invariant mass fits nicely into the proposed framework. In particular, we find a vast parameter space which can lead to the central value for the observed forward-backward asymmetry in the high mass bin, while being in accord with all of the existing experimental constraints.Comment: added discussion of differential observables at the LHC, matches version accepted for publication in JHE