cssi/SciSciGPT-SciSciNet huggingface dataset:
Glycosaminoglycans regulate elastase inhibition by oxidized secretory leukoprotease inhibitor.

Secretory leukoprotease inhibitor (SLPI) is one of the major physiological inhibitors protecting respiratory epithelium from attack by excess human leukocyte elastase (HLE), a serine protease released by neutrophils upon activation in response to inflammatory stimuli. Reaction with N-chlorotaurine, a major long-lived oxidant generated by activated neutrophils, oxidized all four methionine residues, but no other amino acids, in SLPI, resulting in substantial diminution of its elastase inhibitory activity. Oxidation of the P 1 ' residue, Met 73 , accounted for most of the diminution in activity since a site-directed mutant of SLPI with leucine at the P 1 ' position retained much higher residual activity after reaction with N-chlorotaurine. The diminished activity of oxidized SLPI could be almost completely restored when an iduronate-containing glycosaminoglycan, such as heparin, heparan sulfate, or dermatan sulfate, was added to the reaction medium. Addition of sulfated glucuronate-containing glycosaminoglycan, chondroitin 4- or 6-sulfate, to the medium resulted in smaller but significant restoration of the lost activity, whereas the effects of hyaluronic acid and keratan sulfate were negligible. Kinetic analysis revealed that glycosaminoglycans greatly accelerated the association of oxidized SLPI and HLE, whereas iduronate-containing glycosaminoglycans also stabilized the enzyme-inhibitor complex formed. Based on these findings, we suggest that oxidized SLPI is a functionally active form of the inhibitor but that expression of its elastase inhibitory activity is regulated by sulfated uronate-containing glycosaminoglycans. Because its methionine residues have already been oxidized, this form of SLPI is resistant to the oxidant species that selectively attacks methionine residues in proteins. These findings indicate that SLPI may play a previously unexpected role in elastase inhibitory function in the lungs when significant inflammation is present.
Effects of in vivo neuraminidase on the regulation of erythropoiesis. II: Modulation of erythroid colony formation by thymic regulatory cells.

Effects of the enzyme vibrio-cholerae neuraminidase (VCN) on the marrow-derived erythropoietic progenitor CFU-E and thymic regulatory cells were examined in vitro 1 and 24 h after i.v. injection of the enzyme. An in vivo enzymatic modification of bone marrow and thymic helper regulatory cell function occurs within 1 h after i.v. injection of VCN and results in suppression of both CFU-E colony formation and thymic helper cell function. These inhibitory effects of neuraminidase, however, are no longer detectable by 24 h after injection. More importantly, these inhibitory effects can be reversed by adding thymocytes from control animals to cocultures of enzymatically modified marrow or thymic regulatory cells. These findings: 1) suggest that regulatory cells from the bone marrow and thymus may be enzymatically modified in vivo in a reversible manner, suggesting a noncytotoxic effect of the enzyme on accessory cells, and 2) confirm the importance of sialic acid for the helper function but not for the suppressor function of thymocytes and CFU-E colony formation in vitro.
Arginine Supplementation of Sickle Transgenic Mice Leads to a Rapid Decrease in MCHC and Percent Dense Cells and a Slow Increase When Supplementation Is Discontinued.

Nitric oxide (NO) is produced from arginine by nitric oxide synthase (NOS) and is essential to the maintenance of vascular tone. Plasma arginine levels are reduced in sickle cell anemia patients, and we have previously reported that S+S− Antilles mice have lower plasma arginine than control mice (C57BL). Long term arginine supplementation (5% arginine in chow) restored plasma arginine levels in S+S− Antilles mice to that found in C57BL mice, and, in S+S− Antilles mice, MCHC and the percent high density red cells were reduced. Our observation that Ca++-activated K+ channel [K(Ca) channel or Gardos channel] activity is reduced in supplemented vs non-supplemented S+S− Antilles mice can account for reduced red cell density and dense cell formation (Blood 99: 1103, 2002). The time course of arginine induced changes in red cell indices in sickle transgenic mice has not yet been studied. Using the Advia 120 Hematology System, we found that, within 7 days after the onset of arginine supplementation, MCHC* (CHCM in the Advia system) fell from 33.4±0.5 g/dL to 31.0±0.2 (mean ±SD, P 37 g/dL) decreased from 10.5±4.3 % to 4.5±1.6 (P<0.01, N=6). MCV rose from 43.6±0.8 fL to 46.4±0.5 (P<0.00003, N=6). Reticulocyte counts and mean corpuscular hemoglobin did not vary significantly. Although plasma arginine levels increase within a few hours of oral administration and persist for only a few hours, no change in red cell indices was observed 7 days after discontinuing arginine supplementation, and the indices slowly returned to baseline levels after 40 days. In summary, MCHC* and the percent high density RBCs decrease significantly within 7 days of the onset of arginine supplementation. When arginine supplementation is withdrawn, the return to baseline values is much slower and required more than 40 days to complete. These observations have important implications for arginine supplementation in sickle cell anemia patients. In particular, the persistence of decreased MCHC* and reduced percent high density RBCs for an extended period of time after supplementation was withdrawn parallels our previously reported observation of persistent improvement of perfusion in sickle transgenic mice after supplementation was withdrawn and suggests that daily administration of arginine may not be necessary once an induction period has passed.
Messenger RNAs localized to distal projections of human stem cell derived neurons

The identification of mRNAs in distal projections of model organisms has led to the discovery of multiple proteins that are locally synthesized for functional roles such as axon guidance, injury signaling and regeneration. The extent to which local protein synthesis is conserved in human neurons is unknown. Here we used compartmentalized microfluidic chambers to characterize the transcriptome of distal projections of human embryonic stem cells differentiated using a protocol which enriched for glutamatergic neurons (hESC-neurons). Using gene expression analysis, we identified mRNAs proportionally enriched in these projections, representing a functionally unique local transcriptome as compared to the human neuronal transcriptome inclusive of somata. Further, we found that the most abundant mRNAs within these hESC-neuron projections were functionally similar to the axonal transcriptome of rat cortical neurons. We confirmed the presence of two well characterized axonal mRNAs in model organisms, β-actin and GAP43, within hESC-neuron projections using multiplexed single molecule RNA-FISH. Additionally, we report the novel finding that oxytocin mRNA localized to these human projections and confirmed its localization using RNA-FISH. This new evaluation of mRNA within human projections provides an important resource for studying local mRNA translation and has the potential to reveal both conserved and unique translation dependent mechanisms.
Mobile DNA in Health and Disease.

More than half the human genome is derived from transposable elements (also known as mobile DNA or “jumping genes”); some of these elements have been repurposed over time in the service of evolution. “Live” mobile elements are a rare cause of genetic disease.
How Parents Influence Their Children’s Friendships

Friendships are among the central ingredients of children’s lives, from as early as age 3 and, in some cases, even earlier. Children’s relationships with their peers directly affect their well-being, provide an opportunity to learn and practice social skills, and may establish enduring patterns of relating to others (cf. Rubin, 1980). Parents typically recognize the importance of children’s friendships and often try to help their children establish and maintain rewarding friendships. Even parents who have no specific intention of influencing their child’s friendships can hardly avoid doing so, through the settings they choose to live in, their reactions to the child’s social behavior, and the values they convey through their own relationships with others. Whether or not these parental influences are intended, and whether or not they are recognized by the parents themselves, they are among parents’ most important legacies to their children.
Mapping elemental contamination on Palmyra Atoll National Wildlife Refuge

Palmyra Atoll, once a WWII U.S. Navy air station, is now a U.S. National Wildlife Refuge with nearly 50km2 of coral reef and 275ha of emergent lands with forests of Pisonia grandis trees and colonies of several bird species. Due to the known elemental and organic contamination from chemicals associated with aviation, power generation and transmission, waste management, and other air station activities, a screening survey to map elemental concentrations was conducted. A map of 1944 Navy facilities was georeferenced and identifiable features were digitized. These data informed a targeted survey of 25 elements in soils and sediment at locations known or suspected to be contaminated, using a hand-held X-ray fluorescence spectrometer. At dozens of locations, concentrations of elements exceeded established soil and marine sediment thresholds for adverse ecological effects. Results were compiled into a publically available geospatial dataset to inform potential remediation and habitat restoration activities.
Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting.

This article is a report on a symposium entitled “Physiological Regulation of Drug Metabolism and Transport” sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2017 meeting in Chicago, IL. The contributions of physiologic and pathophysiological regulation of drug-metabolizing enzymes and transporters to interindividual variability in drug metabolism are increasingly recognized but in many cases are not well understood. The presentations herein discuss the phenomenology, consequences, and mechanism of such regulation. CYP2D6 transgenic mice were used to provide insights into the mechanism of regulation of this enzyme in pregnancy, via hepatocyte nuclear factor 4α, small heterodimer partner, and retinoids. Regulation of intestinal and hepatic drug-processing enzymes by the intestinal microbiota via tryptophan and its metabolites was investigated. The potential impact of parasitic infections on human drug metabolism and clearance was assessed in mice infected with Schistosoma mansoni or Plasmodium chabaudi chabaudi AS, both of which produced widespread and profound effects on murine hepatic drug-metabolizing enzymes. Finally, the induction of Abcc drug efflux transporters by fasting was investigated. This was demonstrated to occur via a cAMP, protein kinase A/nuclear factor-E2-related factor 2/Sirtuin 1 pathway via antioxidant response elements on the Abcc genes.
Dynamic coupling between conformations and nucleotide states in DNA gyrase.

Gyrase is an essential bacterial molecular motor that supercoils DNA using a conformational cycle in which chiral wrapping of > 100 base pairs confers directionality on topoisomerization. To understand the mechanism of this nucleoprotein machine, global structural transitions must be mapped onto the nucleotide cycle of ATP binding, hydrolysis and product release. Here we investigate coupling mechanisms using single-molecule tracking of DNA rotation and contraction during Escherichia coli gyrase activity under varying nucleotide conditions. We find that ADP must be exchanged for ATP to drive the rate-limiting remodeling transition that generates the chiral wrap. ATP hydrolysis accelerates subsequent duplex strand passage and is required for resetting the enzyme and recapturing transiently released DNA. Our measurements suggest how gyrase coordinates DNA rearrangements with the dynamics of its ATP-driven protein gate, how the motor minimizes futile cycles of ATP hydrolysis and how gyrase may respond to changing cellular energy levels to link gene expression with metabolism. Single-molecule measurements of DNA gyrase activity reveal conformational dynamics coupling ATP consumption to DNA supercoiling.
Ochratoxin/Citrinin as Nephrotoxins

The mycotoxins are a diverse group of secondary fungal metabolites. The diversity of chemical structure suggests that toxic mold metabolites may have the potential to cause diseases either after ingestion or contact on the skin. The mycotoxicoses that result from exposure to these compounds may be expressed as dysfunction of nervous system, the liver, the kidneys or potentially many other organs. Clearly, fungal infestation is not a requirement for the production of mycotoxicoses. Although the ability of certain mycotoxins to alter renal function in man has been debated only relatively recently, human contact with fungal toxins is not a new experience. Bagger (1931) had suggested that the earliest encounter of human mycotoxicoses were the ergotism episodes of the Middle Ages. It is likely that earlier occurrences also happened, but undoubtedly the frequency of such occurrences has decreased considerably in modern times. With the development of modern storage techniques for food, fungal contamination, as well as contamination by other microorganisms, has been greatly reduced and often is not considered a serious problem. Indeed, although human mycotoxicoses have not been ignored in recent times, it is nonetheless true that a much greater effort has been expended to address the problem of fungal contamination of animal feeds.
Unit Processes Against Unit Operations: The Educational Fights of the Thirties

Chemical Engineering started as a discipline concerned with the education of engineers who would work in chemical plants. Yet, in the early days of the development of this field, industrial chemistry was the most “acceptable” method of education of students.
Contextualizing LGB youth's experiences with victimization and risky behaviors: a qualitative approach to general strain theory

This study uses 20 in-depth interviews with lesbian, gay, and bisexual (LGB) young adults aged 18 to 25 years to integrate theoretical constructs from the sociology of sexuality with Agnew’s genera...
Development and validation of diagnostic markers for Fhb1 region, a major QTL for Fusarium head blight resistance in wheat

Functional markers were developed based on the critical sequence deletion of TaHRC in the Fhb1 region and validated to be diagnostic in a worldwide wheat collection. Wheat Fusarium head blight (FHB) is a devastating disease in wheat and barley worldwide. Growing FHB-resistant cultivars is an effective strategy to minimize FHB damage in wheat production. Fhb1 is a quantitative trait locus for FHB resistance with the largest effect on disease severity identified to date. With this study, we developed diagnostic DNA markers for Fhb1 by comparing the genomic sequences in Fhb1 region between near-isogenic lines contrasting in Fhb1 alleles and phenotypic effects of the markers. Two markers were developed based on a deletion mutation in an gene encoding a putative histidine-rich calcium-binding protein (TaHRC) and validated in different types of populations. Haplotype or sequence analyses of the two markers in the three sets of diversity panels demonstrated that they are diagnostic for Fhb1, and superior to all previously used markers in selection accuracy. They also have the advantages of low cost, easy assay, and are suitable for breeding programs with either high- or low-throughput marker laboratories.
Acute Kidney Injury following Cardiac Surgery: A Clinical Model.

Background Scientists use preclinical models of acute kidney injury (AKI) to decipher mechanisms and develop therapy, but translation of therapies to patients remains poor. Models that better resemble patients, including those within clinical care, should be considered. Summary Mice provide many advantages to the study of human disease including an ability to dictate precise experimental conditions. To best isolate and measure phenomena, scientists reduce experimental variability - identical animals, environmental conditions, experimental exposures, and outcome assessments. This technique reduces effect size variability and increases power but dissociates these model organisms from the clinical patients they intend to represent, potentially accounting for the poor translation of findings into patient care. Clinical research, conversely, is often plagued by heterogeneous patients, heterogenous environmental factors, and heterogenous renal insults. A compromise between these 2 extremes - a model of AKI that is more similar to human disease but still provides opportunities for rigorous investigation - should be utilized. Cardiac surgery provides a clinical model for the study of AKI due to mechanism overlap it shares with other clinical conditions (improved generalizability) and characteristics that provide distinct opportunities for research. The high rate of AKI following cardiac surgery and the relative homogeneity (decreased variability) of cardiac surgery subjects, their environment, and renal insults increase power and the opportunity to make discoveries and advance care. Moreover, the elective nature of cardiac surgery provides opportunities to perform detailed baseline assessments and pretreat select patients. Key Messages: Models that better reflect clinical AKI are needed to decipher mechanisms and develop effective treatments. Cardiac surgery is an important clinical model form for the study of AKI.
Examining Performance Assessment: Illuminating Teacher Development and The Construction of a Profession

Mandated teacher performance assessments (TPAs) have recently become a popular form of high-stakes assessment in teacher education. For example, California requires all pre-service teachers to successfully complete a TPA before receiving a preliminary credential, and edTPA, a TPA distributed by Pearson, has been adopted by over 800 teacher education programs in the U.S. High stakes performance assessments are used as gatekeepers, consequently serving as a professionalizing tool. This paper uses sociolinguistics and critical discourse analysis of completed TPAs to explore the vision of the profession that the assessment communicates to novice teachers. Analysis demonstrates how pre-service teachers position themselves as well as how the demands of the assessment position them.
Risk and Protective Factors for Peer Victimization in Adolescents with ADHD

Youth with ADHD are more at-risk for peer victimization than their typically developing peers, and may not be benefiting from current interventions. Thus, we sought to examine risk (i.e., anxiety, ...
Data’s (In)Humanism: Re/presentations of State, Institutions, and Practices in Contemporary Educational Re/search:

This article addresses how researchers have drawn from qualitative methods when engaging with/in liminal populations, with a focus on historically marginalized populations and their rhetorical and ...
Drug-specific differences in the ability of opioids to manage burn pain

Burn injury pain is a significant public health problem. Burn injury treatment has improved tremendously in recent decades. However, an unintended consequence is that a larger number of patients now survive more severe injuries, and face intense pain that is very hard to treat. Although many efforts have been made to find alternative treatments, opioids remain the most effective medication available. Burn patients are frequently prescribed opioids in doses and durations that are significantly higher and longer than standard analgesic dosing guidelines. Despite this, many continue to experience unrelieved pain. They are also placed at a higher risk for developing dependence and opioid use disorder. Burn injury profoundly alters the functional state of the immune system. It also alters the expression levels of receptor, effector, and signaling molecules within the spinal cord's dorsal horn. These alterations could explain the reduced potency of opioids. However, recent studies demonstrate that different opioids signal preferentially via differential signaling pathways. This ligand-specific signaling by different opioids implies that burn injury may reduce the antinociceptive potency of opioids to different degrees, in a drug-specific manner. Indeed, recent findings hint at drug-specific differences in the ability of opioids to manage burn pain early after injury, as well as differences in their ability to prevent or treat the development of chronic and neuropathic pain. Here we review the current state of opioid treatment, as well as new findings that could potentially lead to opioid-based pain management strategies that may be significantly more effective than the current solutions.
Dietary antioxidants and the biochemical response to oxidant inhalation : III. Selenium influence on mouse lung response and tolerance to ozone.

We fed female strain A/St mice selenium (Se) test diets containing either no Se (−Se) or 1 ppm Se (+Se) for 11 wk. Both diets contained 55 ppm vitamin E. We then exposed three groups of mice from each dietary regimen to either 0.8 ppm (1568 μg/m3) O3 (low-level) continuously for 5 d, 10.0 ppm (19,600 μg/m3) O3 (high-level) for 12 h, or filtered room air, where the latter served as a control for both O3 exposures. After O3 exposures we analyzed the lungs for various physical and biochemical parameters, and compared the results to those obtained from the air controls. The results showed that the difference in dietary Se intake produced an eightfold difference in Se content and a three-fold difference in glutathione peroxidase (GP) activity in the lung, but few changes in other lung parameters. With low-level O3 exposure, NADPH production increased significantly in +Se mice, but did not change in −Se mice. With high-level O3 exposure we observed comparable effects for both dietary regimens, including animal mortality, which was 24% for −Se and 14% for +Se mice. Thus, it seems that diminished GP activity resulting from Se deficiency and the ensuing lack of increase in NADPH production were poorly correlated with mouse tolerance to O3. The lung Se content increased in both dietary regimens after O3 exposure, but the increase was greater after high-level O3 exposure. This suggests a “mobilization” of Se to the lung under O3 stress. It is possible that such a mobilization contributes to the lung reserve of antioxidants, and hence the comparable mortality in both dietary Se regimens.
Kinobead/LC-MS Phosphokinome Profiling Enables Rapid Analyses of Kinase-Dependent Cell Signaling Networks

Kinase-catalyzed protein phosphorylation is fundamental to eukaryotic signal transduction, regulating most cellular processes. Kinases are frequently dysregulated in cancer, inflammation, and degenerative diseases, and because they can be inhibited with small molecules, they became important drug targets. Accordingly, analytical approaches that determine kinase activation states are critically important to understand kinase-dependent signal transduction and to identify novel drug targets and predictive biomarkers. Multiplexed inhibitor beads (MIBs or kinobeads) efficiently enrich kinases from cell lysates for liquid chromatography-mass spectrometry (LC-MS) analysis. When combined with phosphopeptide enrichment, kinobead/LC-MS can also quantify the phosphorylation state of kinases, which determines their activation state. However, an efficient kinobead/LC-MS kinase phospho-profiling protocol that allows routine analyses of cell lines and tissues has not yet been developed. Here, we present a facile workflow that quantifies the global phosphorylation state of kinases with unprecedented sensitivity. We also found that our kinobead/LC-MS protocol can measure changes in kinase complex composition and show how these changes can indicate kinase activity. We demonstrate the utility of our approach in specifying kinase signaling pathways that control the acute steroidogenic response in Leydig cells; this analysis establishes the first comprehensive framework for the post-translational control of steroid biosynthesis.
Chronically elevated norepinephrine concentrations lower glucose uptake in fetal sheep

Fetal conditions associated with placental insufficiency and intrauterine growth restriction (IUGR) chronically elevate plasma norepinephrine (NE) concentrations. Our objective was to evaluate the effects of chronically elevated NE on insulin-stimulated glucose metabolism in normally grown, non-IUGR fetal sheep, which are independent of other IUGR-related reductions in nutrients and oxygen availability. After surgical placement of catheters, near-term fetuses received either a saline (control) or NE intravenous infusion with controlled euglycemia. In NE fetuses, plasma NE concentrations were 5.5-fold greater than controls, and fetal euglycemia was maintained with a maternal insulin infusion. Insulin secretion was blunted in NE fetuses during an intravenous glucose tolerance test. Weight-specific fluxes for glucose were measured during a euinsulinemic-euglycemic clamp (EEC) and a hyperinsulinemic-euglycemic clamp (HEC). Plasma glucose and insulin concentrations were not different between groups within each clamp, but insulin concentrations increased 10-fold between the EEC and the HEC. During the EEC, rates of glucose uptake (umbilical uptake + exogenous infusion) and glucose utilization were 47% and 35% lower (P < 0.05) in NE fetuses compared with controls. During the HEC, rates of glucose uptake were 28% lower (P < 0.05) in NE fetuses than controls. Glucose production was undetectable in either group, and glucose oxidation was unaffected by the NE infusion. These findings indicate that chronic exposure to high plasma NE concentrations lowers rates of net glucose uptake in the fetus without affecting glucose oxidation rates or initiating endogenous glucose production. Lower fetal glucose uptake was independent of insulin, which indicates insulin resistance as a consequence of chronically elevated NE.
Autism and Access to Care During the COVID-19 Crisis.

CASE: Brian is a 6-year-old boy who was diagnosed with autism spectrum disorder (ASD) and global developmental delay at age 2. He has no other health conditions of note. Brian lives with his parents and an older brother, who also has ASD, in a rural area 2 hours from the center where he was diagnosed. Brian has a history of intermittent self-injurious behaviors (head-banging, throwing himself onto the floor, etc.) that regularly result in bruising, intense and lengthy tantrums, and aggression toward family and teachers. Brian will occasionally indicate items that he wants, but otherwise has no functional communication skills. Over the past 18 months, Brian's challenging behaviors have waxed and waned. The regional special education program is not equipped to safely manage his behaviors, and there are no in-home or center-based agencies that provide applied behavior analysis (ABA) available. Brian's developmental pediatrician initiated guanfacine (eventually adding a small dose of aripiprazole) and referred the family to psychology for weekly telehealth behavioral parent training to address behavioral concerns using the Research Units in Behavioral Intervention curriculum.Brian's behavioral problems decreased during the initial weeks of the COVID-19 crisis, when he no longer had to leave home or attend special education. However, as summer continued, his behaviors worsened substantially (regular bruising and tissue damage, numerous after-hours consultations with his psychologist and developmental pediatrician, and one trip to the emergency department). The intensity of Brian's behaviors (maintained primarily by access to tangible items and escape from demands) made progress with behavioral supports slow and discouraging for his parents. Other psychosocial stressors coalesced for the family as well, including employment loss, limited social support because of social distancing requirements, and illness of one of his parents. The developmental pediatrician continued to modify the medication regimen over the summer, transitioning Brian from guanfacine to clonidine and increasing his aripiprazole incrementally (with clear increased benefit); hydroxyzine was also used as needed during the episodes of highest intensity.Despite the availability of best-practice guidelines for children with Brian's presenting concerns, a confluence of barriers (geographic, economic, ABA work force, global pandemic, etc.) present serious questions for his family and care team related to the next steps in Brian's care. Should he attend in-person school in the fall, knowing that the available program may have limited educational benefit and increase his risk of COVID-19 exposure (not to mention self-injury)? Would the potential benefits of cross-country travel to an intensive behavioral treatment program outweigh the associated psychosocial and economic stressors? How else can the virtual care team support this family?
Internet use and its impact on internalizing disorder symptoms and sleep in adolescents with an evening circadian preference.

Study Objectives: This study sought to examine the relationship between internet use, sleep, and internalizing disorder symptoms in adolescents with an evening circadian preference. Methods: One hu...
A framework for developing community-focused medical physics outreach programs.

PURPOSE In STEM education and careers, underrepresented minorities (URMs) experience higher attrition than non-URM counterparts. Informal educational experiences, such as outreach, have been identified to increase URM awareness and enrollment in STEM. The objectives of this work were to (1) elucidate the current state of racial and ethnic diversity in medical physics and (2) provide a community-focused framework for building effective outreach programs geared toward K-12 URM students and their families. METHODS Self-reported racial and ethnic identity data from the American Association of Physicists in Medicine (AAPM) members were obtained to identify the percentage of URM members. Outreach programming was developed for home or away events. Home events occurred at the University of Wisconsin-Madison Department of Medical Physics; away events occurred at public community institutions that served URM and economically disadvantaged populations. Demonstrations, hands-on activities, and presentations covered radiation detection, radiotherapy, medical imaging, and medical physics career paths. High school students were asked about their awareness of medical physics prior to outreach events. Likert-scale surveys evaluated student level of agreement (1 = Strongly disagree to 5 = Strongly agree) that home events increased their career interests in medicine and physics and interest in pursuing STEM coursework. RESULTS Average percentage of AAPM URM members was 10.7% from 2014 to 2020. From 2016 to 2020, 42 outreach events occurred near or within the Madison metro area. Over 1900 individuals participated in outreach events, with 50 participants on average per event. The majority of home event participants indicated their interest in medical careers increased (65.4%) and were inspired to pursue more STEM courses (73.1%) after the program. CONCLUSIONS Our medical physics outreach program demonstrates a means of increasing awareness and interest around medical physics, particularly for underrepresented individuals. This article addresses gaps in the literature for how to create and implement effective, community-focused medical physics outreach programs.
Dramatic increase in lever-pressing activity in rats after training on the progressive ratio schedule of cocaine self-administration.

Transition from the highest rate of lever-pressing activity during the unloading (extinction) phase of a cocaine self-administration session to an extremely low activity rate during the remission phase is in many cases gradual. This makes it difficult to assess the duration of the unloading phase after a fixed ratio 1 (FR1) or breakpoint after a progressive-ratio (PR) self-administration session. In addition, 3–5 days of training under the PR schedule results in a dramatic and persistent increase in the rate of presses during PR sessions and in the unloading phase following FR1 self-administration sessions. The goals of this study were to find the definition of the last press demarcating the border between the unloading and remission phases of the session and to determine if this border was also affected by PR training. Rats were trained to self-administer cocaine under the FR1 schedule and then under the PR schedule of drug delivery. Distributions of inter-press intervals (IPIs) during the unloading phase in sessions before and after PR training were compared. It was found that the distribution of cocaine-induced IPIs during the unloading phase was lognormal, bimodal, and independent of previously injected cocaine unit doses. The first mode represented intervals within the short bouts of stereotypic presses and the second mode represented intervals between bouts. The two modes were approximately 0.7 s and 21 s during unloading prior to and 0.6 s and 1.5 s after PR self-administration training. The total number of presses per unloading phase increased eightfold. When the FR1 schedule was restored, the intervals between bouts remained very short for at least 7–10 days and only then started a gradual increase towards baseline levels. The last unloading press was defined as the press followed by the IPI longer than the defined criterion. PR training resulted in a substantial and long-lasting increase in lever-pressing activity during unloading. The duration of the unloading phase did not depend on the rate of lever-pressing activity.
Forest governance and post-conflict peace in Liberia: Emerging contestation and opportunities for change?

Abstract International peacebuilders intervened in post-conflict Liberia to influence the direction of forest governance. Peacebuilders promoted reforms designed to ensure that timber revenues could no longer fuel violence and serve as a catalyst for post-conflict reconstruction. These reforms have been contentious, and have not progressed as expected. The anticipated revenue, employment and community benefits of timber extraction have not materialized, and companies that were awarded concessions have failed to honor their contractual obligations and regularly violated Liberian law. This is because the reforms prioritizing state-centric timber extraction are recreating past arrangements that fostered corruption and patronage and exploited forest communities. This paper argues that these difficulties, along with a concerted effort by international and Liberian advocacy groups to publicize the plight of communities, have led peacebuilders to rethink the privileged status of timber extraction towards a policy goal that affords communities more rights in determining how forests are managed and used. The findings suggest that ready-made solutions for the governance of natural resources can be counterproductive and make peacebuilding more challenging. The findings also suggest that despite the substantial influence of international actors involved in peacebuilding, it is possible to challenge existing narratives that allow new policy choices to emerge
Is the Increasing Volume of Carotid Endarterectomy Justified

To the Editor: I read with interest the recent article by Huber et al1 regarding carotid endarterectomy (CEA) volume in Florida since the Asymptomatic Carotid Atherosclerosis Study (ACAS) advisory was released. In this article, the authors made one statement that is unwarranted. They state in the discussion that “the morbidity and mortality rates reported in the study are consistent with those from multicenter carotid endarterectomy trials.” However, data from Table 5 of their paper would appear to contradict this assertion. In the first report of the North American Symptomatic Carotid Endarterectomy Trial (NASCET),2 the mortality was 0.6%. In the ACAS,3 the perioperative mortality was 0.1%. In the study of Huber et al, the mortality in a mixed population of symptomatic and asymptomatic patients between the ages of 75 and 84 was 1.2%. Above age 84, the mortality was 2.2%. The latter value is close to 4 times higher than the NASCET mortality figure and 22 times higher than the ACAS rate. This is hardly comparable to multicenter trials. High rates of perioperative mortality in elderly patients have also recently been reported by Wennberg and colleagues.4 In their analysis of over 100 000 Medicare beneficiaries undergoing CEA in 1992 and 1993, the 30-day mortality rate was 2.46 for patients between the ages of 80 and 84 and 3.60 in patients over age 85. Huber …
Immunomodulation: a new role for statins?

Statins reduce the expression of the class II major histocompatibility complex (MHCII) by arterial cells, leading to a decreased T-cell response. This indicates that statins may be useful in treating graft atherosclerosis and other chronic inflammatory conditions. ( pages 1399–1402 )
Space geodetic observations and models of postseismic deformation due to the 2005 M7.6 Kashmir (Pakistan) earthquake

We use the L-band Advanced Land Observing Satellite (ALOS) and C-band Envisat interferometric synthetic aperture data and campaign GPS observations to study the postseismic deformation due to the 2005 magnitude 7.6 Kashmir (Pakistan) earthquake that occurred in the northwestern Himalaya. Envisat data are available from both the descending and ascending orbits and span a time period of ~4.5 years immediately following the earthquake (2005–2010), with nearly monthly acquisitions. However, the Envisat data are highly decorrelated due to high topography and snow cover. ALOS data are available from the ascending orbit and span a time period of ~2.5 years between 2007 and 2009, over which they remain reasonably well correlated. We derive the mean line-of-sight (LOS) postseismic velocity maps in the epicentral area of the Kashmir earthquake using persistent scatterer method for Envisat data and selective stacking for ALOS data. LOS velocities from all data sets indicate an uplift (decrease in radar range), primarily in the hanging wall of the earthquake rupture over the entire period of synthetic aperture radar observations (2005–2010). Models of poroelastic relaxation predict uplift of both the footwall and the hanging wall, while models of viscoelastic relaxation below the brittle-ductile transition predict subsidence (increase in radar range) in both the footwall and the hanging wall. Therefore, the observed pattern of surface velocities indicates that the early several years of postseismic deformation were dominated by afterslip on the fault plane, possibly with a minor contribution from poroelastic rebound. Kinematic inversions of interferometric synthetic aperture radar and GPS data confirm that the observed deformation is consistent with afterslip, primarily downdip of the seismic asperity. To place constraints on the effective viscosity of the ductile substrate in the study area, we subtract the surface deformation predicted by stress-driven afterslip model from the mean LOS velocities and compare the residuals to models of viscoelastic relaxation for a range of assumed viscosities. We show that in order to prevent surface subsidence, the effective viscosity has to be greater than 1019 Pa s.
Nitric oxide reduces Ca2+ and Zn2+ influx through voltage-gated Ca2+ channels and reduces Zn2+ neurotoxicity

Abstract The translocation of synaptic Zn2+ from nerve terminals into selectively vulnerable neurons may contribute to the death of these neurons after global ischemia. We hypothesized that cellular Zn2+ overload might be lethal for reasons similar to cellular Ca2+ overload and tested the hypothesis that Zn2+ neurotoxicity might be mediated by the activation of nitric oxide synthase. Although Zn2+ (30–300 μM) altered nitric oxide synthase activity in cerebellar extracts in solution, it did not affect nitric oxide synthase activity in cultured murine neocortical neurons. Cultured neurons exposed to 300–500 μM Zn2+ for 5 min under depolarizing conditions developed widespread degeneration over the next 24 h that was unaffected by the concurrent addition of the nitric oxide synthase inhibitor NG-nitro- l -arginine. Furthermore, Zn2+ neurotoxicity was attenuated when nitric oxide synthase activity in the cultures was induced by exposure to cytokines, exogenous nitric oxide was added or nitric oxide production was pharmacologically enhanced. The unexpected protective effect of nitric oxide against Zn2+ toxicity may be explained, at least in part, by reduction of toxic Zn2+ entry. Exposure to nitric oxide donors reduced Ba2+ current through high-voltage activated calcium channels, as well as K+-stimulated neuronal uptake of 45Ca2+ or 65Zn2+. The oxidizing agents thimerosal and 2,2′-dithiodipyridine also reduced K+-stimulated cellular 45Ca2+ uptake, while akylation of thiols by pretreatment with N-ethylmaleimide blocked the reduction of 45Ca2+ uptake by a nitric oxide donor. The results suggest that Zn2+-induced neuronal death is not mediated by the activation of nitric oxide synthase; rather, available nitric oxide may attenuate Zn2+ neurotoxicity by reducing Zn2+ entry through voltage-gated Ca2+ channels, perhaps by oxidizing key thiol groups.
'Latinas/os' and the Politics of Knowledge Production: LatCrit Scholarship and Academic Activism as Social Justice Action

In this article, Professors Montoya and Valdes examine various ways of developing Latina/o legal studies in the United States. As background, they first outline and examine the three main models of knowledge-production established within legal academia during the past century or so: 1) the traditional or imperial model; 2) the safe-space or vanguard model, and; 3) the big-tent or democratic model. Using this historical template to contextualize current efforts in Latina/o legal studies both substantively and methodologically, they next review the record of LatCrit theorists over the past dozen years. With this analytical framework in place, they situate the LatCrit experiment as an example of the third, or democratic, approach to jurisprudential knowledge production. After discussing LatCrit theory and practices as a key programmatic effort in the development of contemporary Latina/o legal studies, Professors Montoya and Valdes conclude that methods and norms associated with the democratic model are generally best suited for the ongoing cultivation of this field. Nonetheless, Professors Montoya and Valdes counsel LatCrit and allied scholars to mix and match elements of each model to maximize the antisubordination punch of any critical text, project, or program. This strategic yet principled blending of techniques associated with the different knowledge-production models, they conclude more broadly, will generate over time the most incisive body of critical outsider jurisprudence in both individual and collective terms.
Cytokine gene polymorphisms in recurrent spontaneous abortions: a comprehensive review.

Problem Cytokine gene polymorphism studies in women with recurrent spontaneous abortion (RSA) are reviewed to provide comprehensive understanding and a direction for the future investigation. Method of study A search of PubMed was made to identify the published data between 2001 and 2007 regarding RSA and cytokine gene polymorphisms. Results Either allele and/or genotype frequencies of the following polymorphisms were reported to be significantly different between women with RSA and controls: IFN-γ +874AT, TA (P = 0.01), AA (P = 0.04); IL-6, −634CG CG/GG (P = 0.026); IL-10, −592CA CC (P = 0.016); IL-1B −511C (P = 0.035), −31T (P = 0.029); IL-1RA, IL1RN*2 (P = 0.002), and IL1RN*3 (P = 0.002). None of these studies was repeatedly reported by others to be significantly different. Among these, four cytokine polymorphisms (IFN-γ, +874AT; IL-1B −511C; IL-1RA, IL1RN*2, IL1RN*3) were refuted by others and rest of them were studied once. Conclusion Multiple cytokine polymorphisms were reported to be associated with RSA. However, a majority of studies were not confirmed by other investigators or refuted by others. Inconsistent study results might be related to: (i) the production of these cytokines is partly under genetic controls and other factors affect cytokine levels; (ii) ethnic background, environmental factors, and selection criteria for study populations are different and (iii) the possibilities exist that multiple cytokine gene polymorphisms or other genes in linkage disequilibrium may play a role in RSA.
Tax Fairness and Fairness in Tax Data Reporting

A recent Wall Street Journal opinion piece alleged that the Congressional Budget Office had demonstrated that the most affluent Americans "pay too much" in federal taxes. This short paper uses that opinion piece as a foil to explain some of the concepts behind Congressional Budget Office analyses, to review the contributions of different fiscal developments to the shift in relative tax burdens from 2007 to 2009, and to argue that the "progressivity" of a tax system is fundamentally an inquiry into relative rather than absolute norms.
Dopamine Increases Excitability of Pyramidal Neurons in Primate Prefrontal Cortex

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 (n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 microM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 microM) but not significantly altered by the D2 antagonist sulpiride (2.5 microM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.