Microstructure-property relationships in Al-Cu-Li-Ag-Mg Weldalite (tm) alloys, part 2

The microstructure and mechanical properties of the ultrahigh strength Al-Cu-Li-Ag-Mg alloy, Weldalite (tm) 049, were studied. Specifically, the microstructural features along with tensile strength, weldability, Young's modulus and fracture toughness were studied for Weldalite (tm) 049 type alloys with Li contents ranging from 1.3 to 1.9 wt. pct. The tensile properties of Weldalite 049 and Weldalite 049 reinforced with TiB2 particles fabricated using the XD (tm) process were also evaluated at cryogenic, room, and elevated temperatures. In addition, an experimental alloy, similar in composition to Weldalite 049 but without the Ag+Mg, was fabricated. The microstructure of this alloy was compared with that of Weldalite 049 in the T6 condition to assess the effect of Ag+Mg on nucleation of strengthening phases in the absence of cold work

Psychomotor stimulant self administration as a function of dosage per injection in the Rhesus monkey

The relationships between drug dosage per injection and response rate, and drug dosage per injection and total daily drug intake were ascertained in Rhesus monkeys which self-administered cocaine, pipradrol, methylphenidate and phenmetrazine intravenously. The study demonstrated the monkeys would self-administer all of these compounds over a wide range of dosages. Furthermore, the magnitude of reinforcement, i.e., dosage per injection, and the rate of responding in self-administering these compounds were inversely related. However, total daily drug intake was independent of the dosage per injection over a wide range of dosages. The results indicate that either the subjects can compensate for large changes in unit dosage so that daily drug intake remains stable or that a direct effect of these compounds functions in limiting their self-administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46379/1/213_2004_Article_BF00401789.pd

The effects of stimulants and depressants on cocaine self-administration behavior in the Rhesus monkey

The effects of acute intramuscular pretreatment with several dosages of a variety of centrally acting compounds on intravenous cocaine self-administration behavior were ascertained. Pretreatment with morphine and pentobarbital produced no change in this behavior until dosages (2.0 mg/kg and 15.0 mg/kg respectively) were administered which grossly depressed grooming, exploratory, and locomotor activity behaviors, d -amphetamine (0.5–4.0 mg/kg) and phenmetrazine (2.0–12.0 mg/kg) pretreatment produced a dose-related decrease in cocaine self-administration. Trifluoperazine in dosages of 0.01–0.1 mg/kg increased the frequency of this behavior; whereas, higher dosages (0.2, 0.4 mg/kg) grossly depressed behavior. Imipramine (10–50 mg/kg) produced a dose-related decrease in cocaine self-administration. Potential mechanisms of these drug—behavior and drug—drug interactions are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46388/1/213_2004_Article_BF00421274.pd

Acute B-Cell Inhibition by Soluble Antigen Arrays Is Valency-Dependent and Predicts Immunomodulation in Splenocytes

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.9b00328.Antigen valency plays a fundamental role in directing the nature of an immune response to be stimulatory or tolerogenic. Soluble Antigen Arrays (SAgAs) are an antigen-specific immunotherapy that combats autoimmunity through the multivalent display of autoantigen. While mechanistic studies have shown SAgAs to induce T and B-cell anergy, the effect of SAgA valency has never been experimentally tested. Here, SAgAs of discrete antigen valencies were synthesized by click chemistry and evaluated for acute B-cell signaling inhibition as well as downstream immunomodulatory effects in splenocytes. Initial studies using the Raji B-cell line demonstrated SAgA valency dictated the extent of calcium flux. Lower valency constructs elicited the largest reductions in B-cell activation. In splenocytes from mice with experimental autoimmune encephalomyelitis, the same valency-dependent effects were evident in the downregulation of the costimulatory marker CD86. The reduction of calcium flux observed in Raji B-cells correlated strongly with downregulation in splenocyte CD86 expression after 72 hours. Here, a thorough analysis of SAgA antigenic valency illustrates that low, but not monovalent, presentation of autoantigen was ideal for eliciting the most potent immunomodulatory effects.Madison and Lila Self Graduate Fellowship at the University of KansasNIH T32 GM00854

The Making of a Self-Neglect Severity Scale

Research in elder self-neglect has lagged behind that of other forms of mistreatment, despite the fact that self-neglect is the most common allegation reported to Adult Protective Service agencies throughout the US. The lack of a gold-standard to measure self-neglect has hampered efforts to study this phenomenon. Researchers designed the Self-neglect Severity Scale (SSS) based on interviews with Adult Protective Service workers and a national expert panel. The SSS is based on observation and interview and is administered in the home to include an environmental assessment. It was piloted, extensively field tested and then revised. The CREST SSS was developed using survey data and consultation with experts in the field. This instrument utilizes observer ratings, interview responses, and assesses subjects physical and environmental domains. It also assesses functional status as it relates to health and safety issues. After field and pilot testing the SSS was finalized and is currently undergoing reliability and validity testing. The CREST SSS was developed as a state scale to provide a common language for describing cases of self-neglect. It is the first self-neglect severity scale available to researchers. If found to be both reliable and valid it can be used in future intervention studies

Amygdala involvement in self-blame regret

Regret-related brain activity is dependent on free choice, but it is unclear whether this activity is a function of more subtle differences in the degree of responsibility a decision-maker exerts over a regrettable outcome. In this experiment, we show that trial-by-trial subjective ratings of regret depend on a higher subjective sense of responsibility, as well as being dependent on objective responsibility. Using fMRI we show an enhanced amygdala response to regret-related outcomes when these outcomes are associated with high, as compared to low, responsibility. This enhanced response was maximal in participants who showed a greater level of enhancement in their subjective ratings of regret engendered by an objective increase in responsibility. Orbitofrontal and cingulate cortex showed opposite effects, with an enhanced response for regret-related outcomes when participants were not objectively responsible. The findings indicate that the way the brain processes regret-related outcomes depends on both objective and subjective aspects of responsibility, highlighting the critical importance of the amygdala

HST/WFPC2 and VLA Observations of the Ionized Gas in the Dwarf Starburst Galaxy NGC 4214

We present new H alpha and [O III] 5007 narrow band images of the starbursting dwarf galaxy NGC 4214, obtained with the WFPC2 onboard HST, together with VLA observations of the same galaxy. The HST images resolve features down to physical scales of 2-5 pc, revealing several young (<10 Myr) star forming complexes of various ionized gas morphologies (compact knots, complete or fragmentary shells) and sizes (10-200 pc). Our results are consistent with a uniform set of evolutionary trends: The youngest, smaller, filled regions that presumably are those just emerging from dense star forming clouds, tend to be of high excitation and are highly obscured. Evolved, larger shell-like regions have lower excitation and are less extincted due of the action of stellar winds and supernovae. In at least one case we find evidence for induced star formation which has led to a two-stage starburst. Age estimates based on W(H alpha) measurements do not agree with those inferred from wind-driven shell models of expanding H II regions. The most likely explanation for this effect is the existence of a 2 Myr delay in the formation of superbubbles caused by the pressure exerted by the high density medium in which massive stars are born. We report the detection of a supernova remnant embedded in one of the two large H II complexes of NGC 4214. The dust in NGC 4214 is not located in a foreground screen but is physically associated with the warm ionized gas.Comment: 41 pages, including 9 figures and 7 tables. To appear in the November issue of the Astronomical Journa

Food- and drug-reinforced responding: Effects of DITA and d -amphetamine

Intravenous pretreatment with DITA (0.1–1.0 mg/kg) decreased the rate of food-reinforced lever pressing in rhesus monkeys. Response rate decreases were dose-dependent but showed the development of tolerance. Self-administration of DITA was initiated and maintained in each of three monkeys when 30 lever presses were required to produce each injection. Maximal response rate during periods of drug availability was maintained by 0.03 mg/kg/injection while higher and lower doses (0.01 and 0.10 mg/kg/injection) maintained lower response rates. Response rate in periods of food availability immediately preceding drug periods was relatively constant across sessions; response rate in periods of food availability immediately following drug periods, however, decreased with increasing amounts of drug self-administered. Replication of initial self-administration doses produced results comparable to original determinations in contrast to the tolerance observed with DITA effects upon food-reinforced responding. DITA was about 3 times less potent than d -amphetamine in maintaining response rates in drug periods and in decreasing the rate of subsequent food-reinforced responding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46391/1/213_2004_Article_BF00437608.pd

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

About Attitudes and Perceptions: Finding the Proper Way to Consider Latent Variables in Discrete Choice Models

We provide an in-depth theoretical discussion about the differences between attitudes and perceptions, as well as an empirical exercise to analyze its effects. This discussion is of importance, as the large majority of papers considering attitudinal latent variables, just consider those as attributes affecting directly the utility of a certain alternative while systematic taste variations are rarely taken into account and perceptions are normally completely ignored. The results of our case study show that perceptions may indeed affect the decision making process and that they are able to capture a significant part of the variability that is normally explained by alternative specific constants. In the same line, our results indicate that attitudes may be a reason for systematic taste variations, and that a proper categorization of the latent variables, in accordance with the underlying theory, may outperform the customary assumption of linearity