cssi/SciSciGPT-SciSciNet huggingface dataset:
Dantrolene suppresses spontaneous Ca2+ release without altering excitation-contraction coupling in cardiomyocytes of aged mice.

Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca2+ homeostasis including altered Ca2+ cycling through the sarcoplasmic reticulum (SR). The ryanodine receptor antagonist dantrolene exerts antiarrhythmic effects by preventing spontaneous diastolic Ca2+ release from the SR. We tested the hypothesis that dantrolene prevents spontaneous Ca2+ release without altering excitation-contraction coupling in aged myocardium. Left ventricular cardiomyocytes isolated from young (3 to 4 mo) and aged (24–26 mo) C57BL/6 mice were loaded with the Ca2+ indicator fluo-4. Amplitudes of action potential-induced Ca2+ transients at 1-Hz pacing were similar between young and aged mice, yet cell shortening was impaired in aged mice. Isoproterenol (1 μM) increased Ca2+ transient amplitude and cell shortening to identical levels in young and aged; dantrolene (1 μM) had no effect on Ca2+ transients or cell shortening during pacing. Under Ca2+ overload conditions induced with 10 mM extracellular Ca2+ concentration, spontaneous Ca2+ waves were of diminished amplitude and associated with lower SR Ca2+ content in aged versus young mice. Despite no effect in young mice, dantrolene increased SR Ca2+ content and Ca2+ wave amplitude in aged mice. In the presence of isoproterenol following rest from 1-Hz pacing, Ca2+ spark frequency was elevated in aged mice, yet the time to spontaneous Ca2+ wave was similar between young and aged mice; dantrolene decreased Ca2+ spark frequency and prolonged the time to Ca2+ wave onset in aged mice with no effect in young mice. Thus dantrolene attenuates diastolic Ca2+ release in the aged murine heart that may prove useful in preventing cardiac dysfunction.
Ethical Philanthropy in Academic Psychiatry

Objective: From an ethical perspective, psychiatrists cannot accept gifts of significant monetary value from their patients. This guideline raises important questions regarding institutional practices related to gift-giving in academic psychiatry. The first aim of this article is to explain the ethical tensions and shared ethical commitments of the professions of psychiatry and philanthropy. The second aim is to outline a series of steps that may be undertaken to assure ethical philanthropic practices within an institution, including the establishment of a committed advisory workgroup and the creation of ground rules and safeguards for gift-giving. Each situation should be evaluated for “ethical risk,” and specific measures to safeguard donors should be considered. Method: The author outlines methods to manage, minimize, or eliminate conflict of interest issues, including identification and disclosure of conflicting interests, role separation, goal clarification, confidentiality protections, proper timing...
A cell type–restricted mRNA surveillance pathway triggered by ribosome extension into the 3′ untranslated region

The accuracy of eukaryotic gene expression is monitored at multiple levels. Surveillance pathways have been identified that degrade messenger RNAs containing nonsense mutations, harboring stalled ribosomes or lacking termination codons. Here we report a previously uncharacterized surveillance pathway triggered by ribosome extension into the 3′ untranslated region. This ribosome extension–mediated decay, REMD, accounts for marked repression of protein synthesis from a human α-globin gene containing a prevalent antitermination mutation. REMD can be mechanistically distinguished from other surveillance pathways by its functional linkage to accelerated deadenylation, by its independence from the NMD factor Upf1 and by cell-type restriction. This unusual pathway of mRNA surveillance is likely to act as a modifier of additional genetic defects and may reflect post-transcriptional controls particular to erythroid and other differentiated cell lineages.
Gene–environment interactions reexamined: Does mother's marital stability interact with the dopamine receptor D2 gene in the etiology of childhood attention-deficit/hyperactivity disorder?

Potential candidate Gene x Environment interactions in the etiology of childhood attention-deficit/hyperactivity disorder (ADHD) are examined between the dopamine receptor D2 gene (DRD2) and putative family environmental risk factors that reflect mothers' marital stability. Specifically, interactions were tested between DRD2 and mothers' marital status, number of marriages or cohabiting relationships, and age at first marriage. Moderate relations were found among the marital stability measures, and mother's marital status and number of marriages or cohabiting relationships (but not age at first marriage) were risk factors for their children's ADHD. All three mother's marital stability variables were associated with either the child's or mother's DRD2 genotypes. Gene x Environment interactions were found for children's ADHD diagnoses between children's DRD2 genotypes and mother's marital status and number of marriages or cohabiting relationships. It is of interest that these interactions were strengthened with the progressive addition of sets of covariates intended to control for alternative causal pathways that represent background genetic and environmental context confounds. The present findings highlight the importance of considering both the nexus of putative environmental risk factors and whether their etiology and effects are truly environmental in future Gene x Environment interaction research.
Membranoproliferative Glomerulonephritis: Pathogenetic Heterogeneity and Proposal for a New Classification

Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury that results from subendothelial and mesangial deposition of Igs caused by persistent antigenemia and/or circulating immune complexes. The common causes of Ig-mediated MPGN include chronic infections, autoimmune diseases, and monoclonal gammopathy/dysproteinemias. On the other hand, MPGN also can result from subendothelial and mesangial deposition of complement owing to dysregulation of the alternative pathway (AP) of complement. Complement-mediated MPGN includes dense deposit disease and proliferative glomerulonephritis with C3 deposits. Dysregulation of the AP of complement can result from genetic mutations or development of autoantibodies to complement regulating proteins with ensuing dense deposit disease or glomerulonephritis with C3 deposits. We propose a new histologic classification of MPGN and classify MPGN into 2 major groups: Ig-mediated and complement-mediated. MPGN that is Ig-mediated should lead to work-up for infections, autoimmune diseases, and monoclonal gammopathy. On the other hand, complement-mediated MPGN should lead to work-up of the AP of complement. Initial AP screening tests should include serum membrane attack complex levels, an AP functional assay, and a hemolytic assay, followed by tests for mutations and autoantibodies to complement-regulating proteins.
Pick‐up ions at Pluto

Methane molecules escaping from Pluto's atmosphere are ionized, and the resulting ions are picked up by the solar wind. The mass loading associated with this ion pick-up can produce a cometlike interaction of the solar wind with Pluto. Heavy ion gyroradii are as large as a half million km in the weak interplanetary magnetic field that exists at 30 AU, which is about an order of magnitude larger than the size of the 'interaction region'. We have calculated velocity space distributions of pick-up ions using numerically determined ion trajectories. The predicted pick-up ion fluxes are high enough to be detectable by standard charged particle detectors as far upstream of Pluto as 10 exp 6 km.
Family Functioning and Family Typology after an Adolescent or Young Adult’s Sudden Violent Death:

This study compared perceptions of family functioning in families bereaved by an adolescent or young adult child’s sudden violent death (accident, homicide, or suicide), parents’ perceptions of family functioning based on parental role, and described the family typologies represented in a population-based sample of parents. A sample of 135 bereaved parents provided data over three time points. Results of the study showed that bereaved mothers and fathers rated their families as more flexible than did a normative sample, and fathers rated their families as less close than the normative group. Clinical and methodological implications for the findings are discussed.
Pseudo-toxic-shock Syndrome Due to a Drug Reaction

A case is reported of a 13-year-old girl who had an illness initially thought to be toxic shock syndrome but subsequently noted to be a toxic reaction to the anticonvulsant, carbamazepine. The patient was never hypotensive but she was febrile and had a desquamative rash and involvement of three organ systeans. Staphylococcus aureus was recovered from the patient's blood and vagina.
Agency governance and enforcement: the influence of mission on environmental decisionmaking

Administrative agencies seeking to impose sanctions for regulatory violations can handle matters internally or through civil or criminal courts. Organizational culture, legal constraints, and political and private actors may influence governance and hence choice of enforcement venue. An enforcement behavior model is constructed and tested empirically using a 1990–1997 sample of Environmental Protection Agency (EPA) air, water, and hazardous waste penalty cases involving individuals. While EPA's enforcement arm embraces the mission of its regulatory arm—minimizing environmental harm—in part, it also has attributes of a police and prosecution force—specifically deterring (and maximizing social welfare) or incapacitating individual violators. Nevertheless, EPA may fail to minimize violations of and generally deter non-culpable individuals who are affiliated with large firms. © 2002 by the Association for Public Policy Analysis and Management.
Teaching the principles of biotechnology transfer: A service-learning approach

As concerns about genetically modified crops, biotechnology and technology transfer have come to the forefront of media coverage and governmental policies, such issues clearly have implications on the life of every citizen around the world. To combat uncertainties about biotechnology and technology transfer with firsthand knowledge of these subjects, a biotechnology servicelearning course was designed. This class examines interdisciplinary issues regarding the transfer of biotechnology and agricultural and medical technologies through the utilization of didactic and service-learning activities. The course provides a forum to discuss global issues with respect to biotechnology transfer, which are becoming more commonly addressed by scientists, social scientists and politicians in our society. The objectives of this undergraduate course are (1) to broaden the perspective of students on global issues related to technology transfer from developed countries to developing countries, (2) to examine the efficacy of technology transfer to developing countries through case studies, (3) to critically evaluate current opinions regarding the benefits and costs of technology transfer to both developed and developing countries, and (4) to become aware of and involved with community organizations addressing the needs for and methodologies involved in technology transfer to developing countries. Establishing a service-learning evironment During the course term, students are guided through an exploration of interactions between developed countries and developing countries with regards to whether technology can and should be effectively transferred to developing countries to combat current social ills such as hunger, disease and poverty. The course is composed of both lecture and service components and is offered to undergraduates at all levels and of all majors. During the lecture module, brief lectures are dispersed among class discussions throughout the class period. Lectures are designed to present new information and model critical thinking patterns. In-class discussions allow students to present personal views with each other, to collectively synthesize new perspectives on the topics presented in class, and to engage in discussions addressing what responsibilities developed countries have in providing access to the latest advances in agricultural and medical technologies and what approaches to knowledge and wealth sharing are most appropriate. Reflective writing assignments allow students to demonstrate their mastery of concepts discussed in class and to present questions about the lecture and/or discussion material. Most students elect to complete such writings using a guideline provided in class that encourages them to include a summary and evaluation of both materials covered in class and assigned readings, which include journal articles, commentaries and reviews.
Improved Lower Bound on the Indirect Coulomb Energy

For a Coulomb system of particles of charge e, it has previously been shown that the indirect part of the repulsive Coulomb energy (exchange plus correlation energy) has a lower bound of the form — Ce 2/3 ∫ ρ (x) 4/3 dx, where ρ is the single particle charge density. Here we lower the constant C from the 8.52 previously given to 1.68. We also show that the best possible C is greater than 1.23.
Intracellular uptake of poly(ethylene glycol) and folic acid modified magnetite nanoparticles

Superparamagnetic magnetite nanoparticles were surface-modified with poly (ethylene glycol) (PEG) or folic acid, to resist the protein adsorption and avoid their recognition by macrophage cells, and to improve their cell internalization and ability to target specific cells. The nanoparticle uptake into human osteosarcoma cells, MG63, was visualized using both fluorescence and confocal microscopy, and quantified using inductively coupled plasma emission spectroscopy (ICP) measurement. Fluorescence and confocal microscopy results showed that the nanoparticles were internalized into the cells after the cells were cultured for 48h in the medium containing the nanoparticles modified with PEG or folic acid. ICP measurements indicated that both the PEG and folic acid modification increased the amount of the nanoparticle uptake into the cells, in comparison with that of unmodified nanoparticles.
Kinetoplastid RNA-editing-associated protein 1 (REAP-1): a novel editing complex protein with repetitive domains

Kinetoplastid RNA editing consists of the addition or deletion of uridines at specific sites within mitochondrial mRNAs. This unusual RNA processing event is catalyzed by a ribonucleoprotein (RNP) complex that includes editing site-specific endoribonuclease, RNA ligase and terminal uridylnucleotidyl transferase (Tutase) among its essential enzymatic activities. To identify the components of this RNP, monoclonal antibodies were raised against partially purified editing complexes. One antibody reacts with a mitochondrially located 45 kDa polypeptide (p45) which contains a conserved repetitive amino acid domain. p45 co-purifies with RNA ligase and Tutase in a large ( approximately 700 kDa) RNP, and anti-p45 antibody inhibits in vitro RNA editing. Thus, p45 is the first kinetoplastid RNA-editing-associated protein (REAP-1) that has been cloned and identified as a protein component of a functional editing complex.
Chédiak-Higashi Syndrome: An Accelerated Phase with Hereditary Elliptocytosis: Case Report and Review of the Literature

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder which possibly results from defective regulation of fusion of primary lysozomal granules, with delayed microbial killing. 1,2 The condition is characterized by partial oculocutaneous albinism, frequent pyogenic infections, abnormally large granules in the leukocytes and other granule-containing cells (including platelets, melanocytes, renal tubular cells, pneumocytes, gastric cells, hepatocytes, neuronal cells and fibroblasts). 3-5 About 50%80% of patients with CHS enter into an “accelerated phase,” manifested by fever, jaundice, hepatosplenomegaly, lymphadenopathy and widespread lymphohistiocytic organ infiltrates with hemophagocytosis, leading to pancytopenia, hypertriglyceredemia and hemodilution, and bleeding disorders secondary to low platelet and fibrinogen levels. 3,6,7 Attention to the disease was reportedly first drawn in 1940 by a physician who recognized peculiar leukocytes in a four-year-old Cuban girl and referred her to Dr. Chediak. Subsequently in 1952, Chediak described the full clinical and hematological features in four members of the same family. 8 All the children were similarly affected, exhibiting pale hair and photophobia, with frequent infection and lymphadenopathy, and all died at an early age. It was then that the large inclusion-like granules were noted in the blood and bone marrow granulocytes. 9
Parallelism between sulfur and selenium amino acids in protein synthesis in the skin of zinc-deficient rats.

SummaryFeeding animals a diet low in either zinc or selenium causes an abnormal condition of skin and hair. It has been established (7, 8) that the uptake of L-cystine-35S and L-methionine-35S in the skin protein of the ZnD rats was significantly lower than in the zinc-supplemented pair-fed controls (ZnS), i.e., 30 and 60%, respectively. Studies were made to investigate the parallelism between the sulfur (Met and Cyst) and selenium (Se Met and Se Cyst) amino acids in protein synthesis in the skin from ZnD rats. Results indicate that at 24 hr the specific activity (cpm/mg protein) present in the skin of the ZnD rats was 25 and 58% of that of the pair-fed controls, after injection of L-75Se Met and L-75Se Cyst, respectively. No significant differences were observed in the 75Se content of the liver, kidney and muscle between the two groups, which was also true with the sulfur amino acids. These results clearly establish a parallelism between sulfur and selenium amino acids in protein synthesis and strongly s...
The Potentiating Effect of ACTH and of Cortisone on Pressor Response to Intravenous Infusion of L-Nor-Epinephrine.∗:

Summary1. The pressor response to an intravenous infusion of 2.1-13.9 μg per minute of 1-nor-epinephrine was studied, using a constant rate infusion apparatus, in 3 patients before and during the administration of ACTH and cortisone. 2. Striking potentiation of the blood pressure response to nor-epinephrine was noted within 24 hours after administration of 90-180 mg ACTH daily or 150-200 mg cortisone daily. The potentiating effect disappeared within 36 hours after the omission of these agents.
Crozier Formation in the Gymnoascaceae: A Preliminary Note

In April, 1935, some pellets of hair and feathers were found about a buzzard roost near Lock Raven, Maryland. These balls of material, apparently regurgitated by the buzzards, were placed in a moist chamber in the laboratory. About two weeks later a fluffy, yellow, mycelial growth was observed. The fruiting fungus was tentatively identified by Dr. C. L. Shear of the Bureau of Plant Industry as being Arachniotus aureus (Eidam) Schr6ter. When cultures of a fungus regarded as the same species by Nannizzi were obtained from Baarn, Holland, and were compared with the organism from the buzzard castings, it became apparent that the two were quite distinct. A study of the original literature, as well as Saccardo's treatis of members of the family Gymnoascaceae, in the Sylloge Fungorum, shows clearly that the diagnoses are too inadequate to permit certain identification with them of fungi which may be found elsewhere. It seems certain that not only Nannizzi's species and the form from buzzard pellets, but also a dozen other species of the family now under cultivation in this laboratory, are actual bonafide members of the Gymnoascaceae. It is the writer's plan to make comparative studies of these during the next few years. The writer is indebted to Dr. D. S. Johnson for facilities in carrying out his work, to Dr. J. N. Couch for his helpful suggestions, to Dr. C. L. Shear for his continued interest, and to Dr. D. H. Linder for transmission of valuable information.
Laboratory Evaluation of Diflubenzuron, Penfluron, and Bay Sir 8514 as Female Sterilants Against the House

Relative potencies of diflubenzuron, penfluron, and Bay Sir 8514 (2-chloro-N-[[[4-(trifluoromethoxy) phenyl]amino]carbonyl]benzamide) were evaluated as female sterilants against Musca domestica L. by injection. Penfluron and Bay Sir 8514 were more than twice as potent sterilants as diflubenzuron. Penfluron was as potent or more potent than Bay Sir 8514. Moreover, female house flies injected with penfluron or Bay Sir 8514 remained sterile for more than 3 wk, but those injected with diflubenzuron regained fertility partially or completely 10 days post treatment. All 3 compounds prevented egg hatch whether the flies received the injection while they were virgins, after they were inseminated, or after they had laid their 1st batch of eggs.
Comparison of the hydroxylation of zoxazolamine and benzo[a]pyrene in human placenta: Effect of cigarette smoking

The in vitro hydroxylation of zoxazolamine was compared with the hydroxylation of benzo[a]pyrene (BP) in full-term placentas from 11 nonsmokers and from 13 women who smoked cigarettes during pregnancy. Cigarette smoking increased the average zoxazolamine and benzo[a]pyrene hydroxylase activities 13- and 39-fold, respectively. A 59-fold range in benzo[a]pyrene hydroxylase activity and a 28-fold range in zoxazolamine hydroxylase activity were found in the placentas of cigarette smokers. A plot of these two enzyme activities showed that zoxazolamine hydroxylase activity was highly correlated, with benzo[a]pyrene hydroxylase activity in the 24 placentas studied (r = 0.98; p less than 0.001). A strong correlation between the above enzymatic activities was also found in 8 placentas which had been stored for 2 yr at -20 degrees C (r = 0.95; p less than 0.001). The results suggest that benzo[a]pyrene and zoxazolamine are metabolized in the human placenta by the same enzyme or by different systems that are under the same regulatory control.
FLUMAZENIL: The Benzodiazepine Antagonist

SUMMARY: POTENTIAL USES There are several potential uses for flumazenil.21 One is for the reversal of residual benzodiazepine effects after sedation and anesthesia. Flumazenil may permit the anesthesiologist to provide a deeper level of sedation desired by some patients without delaying recovery. Flumazenil can also be used to reverse excess benzodiazepine effects that may unintentionally develop. Flumazenil may be used for the treatment of self-administered benzodiazepine overdose and for the reversal of sedation in the ICU to perform neurologic evaluations and to aid in the weaning from mechanical ventilation. Flumazenil also can help with the differential diagnosis of coma or disorientation to evaluate whether benzodiazepines are a contributory factor. With knowledge of benzodiazepine receptor function and the pharmacology of flumazenil, we can predict its effects and toxicities and better evaluate the addition of flumazenil to our armamentarium.
Legal Theory and Semiotics: The Legal Semiotics Critical Approach

A central theme of the book is the question how to proceed practicing the law when a lawyer has acquired semiotic knowledge and skills. The very same issue is also a direct effect of considering the legal semiotic modus operandi. Semiotic steps in legal work are steps to take in texts. Before lawyers write, they read. What they read, even if it is a string of incoherent words, can be named a text. Everything Peirce said about the sign and its triadic embedding or Greimas about texts, belongs to a lawyer’s semiotic approach. That is an element of a lawyers’ self-awareness and professional attitude. The legal semiotics modus operandi requires no complicated application or sophisticated methods but a sharpened awareness about reading and texts. To be a lawyer begins with listening to- and reading spoken and written texts. Attention is therefore on (1) the particularities of a text, its superstructure, surface and engenderment, (2) on the Greimas squares as exemplified for daily uses in legal practice and (3) on the question why names play such a decisive meaningful role in law.
Pancreatic islet cell transplantation.

Experience with islet transplantation in experimental animals is extensive. These investigations are summarized as a background for the description of clinical experience with allotransplantation and autotransplantation of human islets of Langerhans.
The Lessons that Tolstoy and Father Sergius Hold for Public Administration: Revisiting Three Root Questions

This essay revisits three root questions relevant to public administration: To whom or what does one owe loyalty? Do we need complex institutions? What moral principles should guide public administration? The author draws inspiration from both the life of Leo Tolstoy and his short story titled Father Sergius. The two have many parallels with inherent lessons for individual public administrators. The essay comes to the conclusion that the principle of the good example can serve as a paradigm for the field of ethics.
PKC-epsilon deficiency alters progenitor cell populations in favor of megakaryopoiesis.

Background It has long been postulated that Protein Kinase C (PKC) is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCe remains elusive. Objective To delineate the role of PKCe in megakaryopoiesis. Approach and results We used a PKCe knockout mouse model to examine the effect of PKCe deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution. We also investigated platelet recovery in PKCe null mice and TPO-mediated signaling in PKCe null megakaryocytes. PKCe null mice have higher platelet counts due to increased platelet production compared to WT littermate controls (p<0.05, n = 8). Furthermore, PKCe null mice have more bone marrow megakaryocyte progenitor cells than WT littermate control mice. Additionally, thrombopoietin-mediated signaling is perturbed in PKCe null mice as Akt and ERK1/2 phosphorylation are enhanced in PKCe null megakaryocytes stimulated with thrombopoietin. Finally, in response to immune-induced thrombocytopenia, PKCe null mice recovered faster and had higher rebound thrombocytosis than WT littermate control mice. Conclusions Enhanced platelet recovery could be due to an increase in megakaryocyte progenitor cells found in PKCe null mice as well as enhanced thrombopoietin-mediated signaling observed in PKCe deficient megakaryocytes. These data suggest that PKCe is a negative regulator of megakaryopoiesis.
STUDIES ON HUMAN PREMATURE BIRTHS. II. IN VIVO EFFECT OF SMOKING AND IN VITRO EFFECT OF NICOTINE ON HUMAN UTERINE CONTRACITILITY.

Abstract 1. To the best of our knowledge, for the first time, in 17 gravidas near term in vivo effect of cigarette smoking has been reported objectively on the spontaneous activity of the human uterus. The effect of nicotine, per se, has also been evaluated on human pregnant and nonpregnant myometrial strips. 2. In more than half of the gravidas near term a definite increment in uterine activity was noticed during cigarette smoking. However, nicotine in vitro experiments on human myometrial strips did not show any oxytocic effect. 3. The significance and the mechanism of action of smoking on uterine contractility have been discussed.
A Data-Driven Methodology for Probabilistic Wind Power Ramp Forecasting

With increasing wind penetration, wind power ramps (WPRs) are currently drawing great attention to balancing authorities, since these wind ramps largely affect power system operations. To help better manage and dispatch the wind power, this paper develops a data-driven probabilistic WPR forecasting (p-WPRF) method based on a large number of simulated scenarios. A machine learning technique is first adopted to forecast the basic wind power forecasting scenario and produce the historical forecasting errors. To accurately model the distribution of wind power forecasting errors, a generalized Gaussian mixture model is developed and the cumulative distribution function (CDF) is also analytically deduced. The inverse transform method based on the CDF is used to generate a large number of forecasting error scenarios. An optimized swinging door algorithm is adopted to extract all the WPRs from the complete set of wind power forecasting scenarios. The p-WPRF is generated based on all generated scenarios under different weather and time conditions. Numerical simulations on publicly available wind power data show that the developed p-WPRF method can predict WPRs with a high level of reliability and accuracy.
The role of adenosine 1a receptor signaling on GFR early after the induction of sepsis

Sepsis and acute kidney injury (AKI) synergistically increase morbidity and mortality in the ICU. How sepsis reduces glomerular filtration rate (GFR) and causes AKI is poorly understood; one propos...
Out of proportion pulmonary hypertension in obstructive lung diseases.

Purpose of review Pulmonary hypertension is common (25-90%) in chronic obstructive pulmonary diseases (COPDs). Severe pulmonary hypertension, however, is quite rare (1-3%). The term 'out of proportion' pulmonary hypertension is still widely used. New guidelines instead propose to use the term 'Severe pulmonary hypertension' if mean pulmonary arterial pressure at least 35 mmHg or cardiac index (CI) is less than 2.0 l/min/m on right heart catheterization (RHC). Why only a minority of COPD patients develop severe pulmonary hypertension is unclear. Recent findings When present, severe pulmonary hypertension in COPD is associated with increased dyspnea and decreased survival and often does not closely correlate with degree of obstructive abnormality on pulmonary function testing. COPD patients with severe pulmonary hypertension experience circulatory limitation at maximum exercise, and not ventilatory limitation, which is typical for moderate-to-severe COPD patients with no or moderate pulmonary hypertension. Summary There is no conclusive evidence to support or completely reject the possibility of the use of specific pulmonary arterial hypertension (PAH) therapies in pulmonary hypertension associated with COPD. In mild-to-moderate COPD patients who have severe and progressive symptoms, and have evidence of severe pulmonary hypertension on RHC, specific PAH therapies may be used similar to WHO group-I PAH guidelines.
Dialogue as Meaning-Making

Virginia Woolf (1929) recognized and respected the inherent capability of language to embody an individual’s innermost values, beliefs, fears, and aspirations. In this sentence, she advises young writers that to be successful, they must understand that their words need to be portals to their intrinsic reality. Language has the capability to integrate one’s inner being with the outer world which surrounds them.
What defines a clinically meaningful outcome in the treatment of substance use disorders: reductions in direct consequences of drug use or improvement in overall functioning?

Background Sustained abstinence is currently the only accepted end-point for pharmacotherapy trials for most substance use disorders (SUD), with the exception of alcohol. Despite recent efforts, the identification of a non-abstinence alternative as a clinically meaningful end-point for drug use trials has been elusive. Argument and analysis The current standard for establishing a clinically meaningful outcome in SUD trials is to demonstrate that a reduction in drug use is associated with improvement in long-term functioning, but data indicate relatively weak associations between drug use and various psychosocial problem domains. This may be because assessments used most commonly to measure an individual's functioning do not specify whether aspects of functioning are a direct consequence of drug use. The acceptance of a non-abstinence-based end-point for alcohol use disorder trials was supported in part through associations with reductions in alcohol-related consequences, although measures designed to assess the direct consequences of drug use are rarely included in drug treatment efficacy trials. Conclusions The field of substance use disorders should include measures of negative psychosocial and health consequences of drug use, as opposed to overall functioning, in the effort to establish meaningful non-abstinence-based end-points.
Dynamics of Cerebrovascular Responses to Oxygen

The generation of vasoactive metabolites (Siesjo et al, 1971; Kogure et al, 1977) and ions (Dora et al, 1979) or their release into the extracellular space provides an ample explanation for the accompanying cerebrovascular dilation when arterial PO2 (PaO2) is reduced below 40 torr (Borgstrom et al, 1975). However, changes in cerebral blood flow (CBF) with alterations in PaO2 between 50 torr and higher which may reduce local cortical CBF (1CBF) by 80% (Leniger-Follert et al, 1976) are unexplained by changes in brain lactate and other metabolites (Siesjo et al, 1971: Kogure et al, 1977; Dora et al, 1979). Changes in 1CBF, brain tissue PO2 (PtO2), and pH have not been systematically studied over PaO2s ranging tram hyperoxia to moderate hypoxia. Our aim in this study was to determine whether changes in brain hydrogen ion concentration ((H+)) could account for alterations in cerebrovascular tone when PaO2 is reduced from hyperoxic to moderately hypoxic levels. Local tissue steady-state measurements over a wide range of PaO2 may provide a higher resolution than whole brain or regional measurements and enable the detection of more subtle changes than abrupt, acute and severe hypoxic insults (Dora et al, 1979).
Trends in Rates of Lower Extremity Amputation Among Patients With End-stage Renal Disease Who Receive Dialysis.

Importance Patients with end-stage renal disease (ESRD) who receive dialysis are at high risk of lower extremity amputation. Recent studies indicate decreasing rates of lower extremity amputation in non-ESRD populations, but contemporary data for patients with ESRD who receive dialysis are lacking. Objectives To assess rates of lower extremity amputation among patients with ESRD who receive dialysis during a recent 15-year period; to analyze whether those rates differed by age, sex, diabetes, or geographic region; and to determine 1-year mortality rates in this population after lower extremity amputation. Design, Setting, and Participants This retrospective study of 3 700 902 records obtained from a US national registry of patients with ESRD who receive dialysis assessed cross-sectional cohorts for each calendar year from 2000 through 2014. Adult patients with prevalent ESRD treated with hemodialysis or peritoneal dialysis covered by Medicare Part A and B on January 1 of each cohort year were included. Data analysis was conducted from August 2017 to April 2018. Exposures Age, sex, diabetes, and hospital referral region. Main Outcomes and Measures Annual rates per 100 person-years of nontraumatic major (above- or below-knee) and minor (below-ankle) amputations. Results For each annual cohort, there were fewer women (47.5% in 2000, 46.2% in 2005, 44.9% in 2010, and 44.0% in 2014) than men, more than half the patients were white individuals (58.1% in 2000, 56.9% in 2005, 56.9% in 2010, and 56.7% in 2014), and a small proportion were employed (13.9% in 2000, 15.1% in 2005, 16.1% in 2010, and 16.5% in 2014). The rate of lower extremity amputations for patients with ESRD who receive dialysis decreased by 51.0% from 2000 to 2014, driven primarily by a decrease in the rate of major amputations (5.42 [95% CI, 5.28-5.56] in 2000 vs 2.66 [95% CI, 2.59-2.72] per 100 person-years in 2014). Patients with diabetes had amputation rates more than 5 times as high as patients without diabetes. Patients younger than 65 years had higher adjusted amputation rates than older patients, and men had consistently higher adjusted amputation rates than women. Adjusted 1-year mortality rates after lower extremity amputation for patients with ESRD who receive dialysis decreased from 52.2% (95% CI, 50.9%-53.4%) in 2000 to 43.6% (95% CI, 42.5%-44.8%) in 2013. In general, amputation rates decreased among all regions from 2000 to 2014, but regional variability persisted across time despite adjustment for differences in patient demographics and comorbid conditions. Conclusions and Relevance Although rates of lower extremity amputations among US patients with ESRD who receive dialysis decreased by 51% during a recent 15-year period, mortality rates remained high, with nearly half of patients dying within a year after lower extremity amputation. Our results highlight the need for more research on ways to prevent lower extremity amputation in this extremely high-risk population.
Fifth International Conference on Remediation of Contaminated Sediments

The International Conference on Remediation of Contaminated Sediments addresses the challenges of combining scientific and engineering advances with assessment and management frameworks and governing policies and regulations to achieve environmental protection goals in sediments remediation and containment. It is attended by scientists, engineers, regulators, site owners, and other environmental professionals representing universities, government agencies, consultants, and R&D and service firms from around the world. The first meetings in this series were held in Venice (2001, 2003), New Orleans (2005), and Savannah (2007).
Talking, reading, and writing like an educational psychologist: The role of discourse practices in graduate students' professional identity development

Abstract This study explored the role played by the development of discourse practices specific to a discipline in the professional identity development of graduate students. Qualitative methods were used to track 34 students at different stages of their doctoral programs, marked by important signposts of progress in their graduate studies in educational psychology. Grounded theory methods led to two themes: (a) students recognizing to varying degrees the need to change their ways of talking, reading, and writing, grounded in experiences with coursework, research activities, practicum sites, and various writing projects; and (b) formal and informal learning communities acting as sites to encourage students' development of disciplinary communication skills, including oral and written forms, as well as their professional identity. Findings highlighted how social science graduate students, throughout their program, developed their professional identity even as they acquired disciplinary discourse practices relevant to various professional situations they encounter.
Protective and therapeutic effects of exercise on stress-induced memory impairment

The objective of this paper was to systematically evaluate the potential preventive and therapeutic effects of exercise in attenuating stress-induced memory impairment. A systematic review was employed, searching PubMed, PsychInfo, Sports Discus and Google Scholar databases. For eligibility, studies had to be published in English, employ an experimental design, have the acute or chronic bout of exercise occur prior to, during or after the stressor, implement a psychophysiological stressor, and have an assessment of memory function occurring after the stressor. In total, 23 studies were evaluated, all of which were conducted among animal models. All 23 studies employed a chronic exercise protocol and a chronic stress protocol. Eight studies evaluated a preventive model, three employed a concurrent model, ten studies employed a therapeutic model, and two studies evaluated both a preventive and therapeutic model within the same study. Among the eight studies employing a preventive model, all eight demonstrated that the stress regimen impaired memory function. In all eight of these studies, when exercise occurred prior to the stressor, exercise attenuated the stress-induced memory impairment effect. Among the ten studies employing a therapeutic model, one study showed that the stress protocol enhanced memory function, one showed that the stress protocol did not influence memory, and eight demonstrated that the stress regimen impaired memory function. Among the eight studies showing that the stress protocol impaired memory function, all eight studies demonstrated that exercise, after the stressor, attenuated stress-induced memory impairment. Within animal models, chronic stress is associated with memory impairment and chronic exercise has both a preventive and therapeutic effect in attenuating stress-induced memory impairment. Additional experimental work in human studies is needed. Such work should also examine acute exercise and stress protocols.
The MYC Enhancer-ome: Long-Range Transcriptional Regulation of MYC in Cancer.

MYC is one of the most important oncogenes in cancer. Indeed, MYC is upregulated in 50–60% of all tumors. MYC overexpression can be achieved through a variety of mechanisms, including gene duplications, chromosomal translocations, or somatic mutations leading to increased MYC stability. However, recent studies have identified numerous tissue-specific noncoding enhancers of MYC that play major roles in cancer, highlighting long-range transcriptional regulation of MYC as a critical novel mechanism leading to MYC hyperactivation and as a potential target for new therapeutic strategies in the near future. Here we summarize the regions and mechanisms involved in the long-range transcriptional regulation of MYC, underscoring the relevance of MYC enhancers both in normal physiological development and in MYC-driven cancer initiation and progression.
Do age and mating status affect olfactory response of the parasitoid, Microplitis croceipes (Hymenoptera: Braconidae) to host-related plant odors?

Background: Parasitic wasps (parasitoids) use volatile organic compounds released by herbivore-infested plants to locate their hosts. Response of parasitoids to plant odors may be plastic and dependent on their physiological state. Using Microplitis croceipes (Hymenoptera: Braconidae), a relatively specialized larval endoparasitoid of Heliothis virescens (Lepidoptera: Noctuidae), we asked whether age and mating status of parasitoids affect their olfactory response to host-related odors. Methods: Four odor stimuli of varying complexity were selected based on previous reports of parasitoid response to cotton volatiles: cis -3-hexenol (a green leaf volatile), α-pinene (a constitutive monoterpene), a 50/50 v/v binary mixture ( cis -3-hexenol + α-pinene), and H. virescens -infested cotton odors. Female M. croceipes used in Y-tube olfactometer bioassays were either mated or unmated, and grouped 1–3, 4–6, and 7–9 d-old. Female parasitoids used in electroantennogram (EAG) recording were mated and grouped 1–3, 4–6, 7–9 and 10–12 d-old. Results: In Y-tube olfactometer bioassays, neither age nor mating status played a major role in the attraction of parasitoids to test odor stimuli, with two exceptions: 4–6 d-old mated parasitoids showed attraction to the binary mixture, and 1–3 d-old mated parasitoids showed attraction to H. virescens -infested cotton. Age did not affect EAG response of parasitoids to test stimuli. Conclusions: The present results suggest that age and mating status do not play a major role in modulating olfactory responses of M. croceipes to host-related plant odors. Instead, plasticity of olfactory response may be limited in M. croceipes due to strong innate sensitivity to host-related odor cues.
Will Planetary Defense Change a Realist World

The emergence of international cooperation and a space epistemic community focused on advancing planetary defense is an unheralded accomplishment of the twenty-first century. The saga of planetary defense has even exceeded the dreams of functionalists, who believed that cooperation on technical matters could bridge political and social differences to tackle problems that afflicted humankind. Nevertheless, it would appear that planetary defense has not sparked a fundamental change in political thinking on Earth, or actually requires that sort of change to be successful. Defenses have advanced despite the existence of a world dominated by nation-states and traditional diplomatic norms and balance of power thinking. It remains to be seen, however, if further advances in space exploration in general and planetary defenses in particular will spark a more Cosmopolitan outlook, leading to the rise of Cosmopolitan institutions on Earth.
Book Review: Golden Kingdoms: Luxury Arts in the Ancient Americas by Joanne Pillsbury, Timothy Potts and Kim N. Richter

Golden Kingdoms: Luxury Arts in the Ancient Americas , by Joanne Pillsbury, Timothy Potts and Kim N. Richter. Los Angeles: Getty Museum, 2017, 328 pp., 428 color illus., 4 maps. $59.95 (cloth), ISBN 9781606065488. Reviewed by Julia Guernsey. Golden Kingdoms: Luxury Arts in the Ancient Americas is
One Message, Many Translations: Heterogeneity Revealed with Multicolor Imaging

mRNA translation and its regulation shape the human proteome. Lyon et al. (2019) and Boersma et al. (2019) introduce new orthogonal peptide-tagging systems to study translation in multiple reading frames. Both groups discovered diverse translation behavior of single mRNAs derived from the same genes.
A Price for Democracy? Religious Legislation and Religious Discrimination in Post-Soeharto Indonesia

Various studies have expressed concerns about the decline of religious freedom in Indonesia. These studies suffer from three limitations. First, they inadequately differentiate between various aspe...
A bio-pen for direct writing of single molecules on user-functionalized surfaces

Advancing ultrahigh resolution (below 10 nm) direct writing technologies could lead to impacts in areas as diverse as disease detection, genetic analysis and nanomanufacturing. Current methods based on electron-beams and photo- or dip-pen nanolithography are laborious and lack flexibility when aiming to create single molecule patterns for application specific integration. We hypothesize that a novel strategy could be developed to allow for writing of parallel and yet individually addressable patterns of single molecules on user-controlled surfaces. The strategy is based on using in vitro self-recognition of tubulin protein to assemble rigid protofilaments of microtubules, with one such microtubule to be subsequently used as a “bio-pen” capable of writing “inks” of single kinesin molecules in user-defined environments. Our results show that single kinesin inks could be written under the energy of adenosine triphosphate hydrolysis and observed by both atomic force and optical microscopy. Upon extending ink functionalities, the integration of soft and hard materials for nanostructure assembly and complex single molecule pattern formation is envisioned.
Checkpoint inhibitor-induced sarcoid choroidal granulomas.

Abstract Purpose To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma. Observations A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy. Conclusion Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event.