cssi/SciSciGPT-SciSciNet huggingface dataset:
Sanguinate: A Novel Blood Substitute Product

Tissue hypoxia secondary to profound anemia can lead to end organ damage with irreversible morbidity and mortality. Patients may choose not to receive blood products for religious reasons or may be unable to receive blood products due to alloimmunization. Artificial blood products have been explored as options for an alternative for blood transfusions, and prior synthetic oxygen carriers have been associated with an increased risk of myocardial infarction and stroke. Sanguinate is purified bovine hemoglobin (Hgb) that has been pegylated and combined with carbon monoxide which may suppress vasoconstriction and provide anti-inflammatory effects. The bovine hemoglobin then carries oxygen for release to areas with a low partial pressure of oxygen. Administration to 29 patients under FDA emergency provisions showed clinical improvements in one or more conditions in 86% of patients and no serious adverse events. Increases in blood pressure of 10-20 mmHg were seen with prior Sanguinate infusions presumably due to the colloid osmotic pressure of the pegylated protein solution. Some of the patients with elevated blood pressures developed fluid overload and increased troponin levels, especially the patients with end stage renal disease. Further efficacy and safety data are needed. From November 2015 through April 2016, Sanguinate was prophylactically administered to adults with profound anemia on 26 occasions at Pennsylvania Hospital with the goal of preventing hypoxic events. Inclusion criteria included: age > 18, a Hgb Average patient age was 62 years (range 21-90.) Average pre- treatment Hgb was 4.3 g/dL (range 2.2- 5.9 g/dL.) Overall survival was 61.5%. Table 1 contains a full list of patient characteristics. No serious adverse events, defined as death, a life-threatening adverse event, disruption in ability to conduct normal life functions, or prolongation of hospitalization, were attributed to Sanguinate; ten deaths were attributed to end organ damage related to profound anemia. Of the patients who survived, there were no long-term deficits, including injuries secondary to hypoxia, observed. Sanguinate administration before irreversible hypoxic events has the potential to bridge episodes of acute anemia in patients for whom blood is not an option and may address an unmet medical need with the potential to improve outcomes. Disclosures No relevant conflicts of interest to declare.
The Radiopharmaceutical Chemistry of the Radioisotopes of Iodine

Radioisotopes of iodine have been incorporated into a wide variety of radiopharmaceuticals ranging from small, low molecular weight compounds to large molecules like antibodies. Because of the routine availability of radioisotopes of iodine with different nuclear decay properties, radioiodination is an attractive strategy because the same chemistry can be utilized for both radionuclide imaging and targeted radiotherapy. Over the years, various methods have been developed for the synthesis of radioiodinated compounds. This chapter gives an overview of these methods as well as their potential advantages and disadvantages. Some useful tips and tactics for the radioiodination chemistry are provided. Important milestones in radioiodination chemistry are summarized and some thoughts about the future of radioiodination as a radiopharmaceutical chemistry strategy are provided.
Impact of Selector Devices in Analog RRAM-Based Crossbar Arrays for Inference and Training of Neuromorphic System

The impact of selector devices on the inference and training accuracy of a resistive random access memory (RRAM)-based neuromorphic computing system is rarely studied. In this paper, we analyze the weighted sum and weight update functions in a one-selector–one-RRAM (1S–1R)-based crossbar arrays. We first develop a Verilog-A model based on the lateral evolution of the filament to describe analog conductance tuning in the filamentary RRAM. We then perform an array-level SPICE simulation on the 1S–1R arrays, where the exponential and threshold selectors are employed. In the inference stage, the read-out current is vulnerable to the inevitable IR drop caused by the wire resistance. Our finding reveals that the use of a threshold selector allows the 1S–1R device to have a linear I–V relation, improving the immunity to the IR drop. On the other hand, the threshold selector distorts analog RRAM’s linear weight update during the training stage. Instead, an introduction of exponential selector enables the desirable properties of analog RRAM to be maintained even in the 1S–1R device. These results indicate that different selectors suitable for each operation mode (inference or training) are preferred in the neuromorphic computing system.
Spirit in Flames

The question about the relationship between ecology, the “science of the household” as the word’s etymology suggests, and lifeworld (Lebenswelt), originally Edmund Husserl’s term (in Crisis in European Science and Transcendental Phenomenology) referring to the phenomenology of human experience, requires that both concepts be reconsidered, for “ecology” is largely a concept based on the metaphysics and “systems” theory of modern science, on the one hand, and “life-world,” as the quotation above suggests, functions as a foundation for phenomenology, on the other. “The Lebenswelt is the object of an immediate experience (intuition), which is the necessary point of departure of phenomenological research,” comments James Edie in Edmund Husserl’s Phenomenology (Edie, 1987, pp. 84–85). Indeed, as Edie points out, Husserl defines phenomenology as Ruckgang auf die Lebenswelt,“a going-back to the prepredicative or prethematic region of experience which is prior to any thought about experience” (84). Both ecology, especially in its evolutionary dimension, and phenomenology, especially in regard to the lifeworld, share a quest for origins, to answer the basic question, “Whence did we and our world come about?” Evolutionary ecology looks at the question “objectively,” phenomenology “subjectively,” and this dichotomy, with its metaphysics and discourse communities, has largely come to characterize the rift between the sciences and the humanities, respectively.
The Interactions Between the Mechanistic Target of Rapamycin (Mtor) and the Microbiome

Type 2 Diabetes mellitus (T2DM) is one of the most prevalent diseases and is associated with several co-morbidities, including obesity, metabolic syndrome, and cardiovascular complications. The mechanistic Target of Rapamycin (mTOR) is a highly conserved protein kinase that integrates inputs from nutrients, insulin, growth factors, and environmental cues to control cellular metabolism. mTOR is dysregulated in insulin resistance and T2DM. Recent studies reveal that the gut microbiome interacts with mTOR to modulate nutrient absorption and homeostasis, but the mechanisms are not understood. mTOR nucleates two distinct complexes, namely mTORC1 and mTORC2, to regulate cell metabolism. mTORC1 receives inputs from nutrients and transmits signals to promote anabolic cell growth and inhibit catabolic autophagy. While mTORC2 phosphorylates Akt downstream of the insulin signaling pathway to regulate cell proliferation. Both mTORC1 and mTORC2 complexes network with multiple signaling pathways to control cellular growth, metabolism, and homeostasis. Recent advances in genomics, proteomics, and metabolomics research enabled identifying several gut microbiota species. These big data resources shed light on the interactions between the gut microbiome, dysbiosis, and mTOR in diabetes, metabolic syndrome, and obesity pathogenesis.
3D human nonalcoholic hepatic steatosis and fibrosis models

This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic studies. Using a photolithographic biofabrication method with a photomask featuring hexagonal units, liver cells, including a human hepatic cell line (HepG2-C3A) and a human hepatic stellate cell line (LX-2) were embedded in gelatin methacryloyl hydrogel. Hepatic steatosis was induced by supraphysiological concentration of free fatty acids; hepatic fibrosis was induced by transforming growth factor-β1. Induction of steatosis was confirmed by Oil Red O and BODIPY staining and was inhibited with toyocamycin and obeticholic acid. Induction of fibrosis was confirmed by immunostaining for collagen type I and alpha smooth muscle actin and inhibited by rapamycin and curcumin treatment. This model was further preliminarily validated using primary human hepatocytes in a similar setup. These constructs provide a viable, biologically relevant, and higher throughput model of hepatic steatosis and fibrosis and may facilitate the study of the mechanisms of disease and testing of liver-directed drugs.
Intrinsically disordered substrates dictate SPOP subnuclear localization and ubiquitination activity.

Speckle-type POZ protein (SPOP) is a ubiquitin ligase adaptor that binds substrate proteins and facilitates their proteasomal degradation. Most SPOP substrates present multiple SPOP-binding (SB) motifs and undergo liquid–liquid phase separation with SPOP. Pancreatic and duodenal homeobox 1 (Pdx1), an insulin transcription factor, is downregulated by interaction with SPOP. Unlike other substrates, only one SB motif has previously been reported within the Pdx1 C-terminal intrinsically disordered region (Pdx1-C). Given this difference, we aimed to determine the specific mode of interaction of Pdx1 with SPOP and how it is similar or different to that of other SPOP substrates. Here, we identify a second SB motif in Pdx1-C, but still find that the resulting moderate valency is insufficient to support phase separation with SPOP in cells. Although Pdx1 does not phase separate with SPOP, Pdx1 and SPOP interaction prompts SPOP relocalization from nuclear speckles to the diffuse nucleoplasm. Accordingly, we find that SPOP-mediated ubiquitination activity of Pdx1 occurs in the nucleoplasm and that highly efficient Pdx1 turnover requires both SB motifs. Our results suggest that the subnuclear localization of SPOP–substrate interactions and substrate ubiquitination may be directed by the properties of the substrate itself.
Cooperative Target protection from a superior Attacker

Abstract The problem of cooperative protection in the presence of a superior opponent is considered. The note addresses the Target–Attacker–Defender problem. The challenging case where the Attacker is faster than the Target and the Defender and also more lethal than the Defender is considered. This note presents novel cooperative strategies for the Target and Defender where they need to rendezvous and to coordinate their close range strategy in order to deny capture of the Target by the Attacker.
Environmental Conditions to Promote Healthy Childhood Brain/Behavioral Development: Informing Early Preventive Interventions for Delivery in Routine Care

Abstract Environmental experiences early in life have strong and enduring consequences for cognitive, emotional, and neurobiological development and related physical and mental health trajectories. The powerful influence of early caregiver nurturance and stimulation on promoting positive neurodevelopmental outcomes has been demonstrated across species. These findings elucidate the environmental conditions known to facilitate healthy neurodevelopment and underscores the potential for modifiable psychosocial factors in the environment to be harnessed to inform early preventive interventions to promote health and adaptive development. A framework for early preventive interventions to enhance nurturing and responsive caregiving for implementation during early sensitive periods of brain development delivered within existing health or educational infrastructures is proposed. Emotional development during sensitive periods is an important, under-recognized, and abundantly modifiable predictor of mental and physical health outcomes that warrants investment of resources, and integration of interventions into public health infrastructure for children worldwide. Future studies are needed to further clarify whether and when sensitive periods are present for key developmental domains to inform the optimal timing and targets of these interventions. Numerous available empirically supported early interventions may be modified and applied in briefer and more feasible modalities of delivery to broader populations of developing children. As well established in growth and development across species, essential environmental inputs that are particularly important at specified developmental periods facilitate optimal growth trajectories. Such principles hold great potential in application to early child neurodevelopment to facilitate a thriving and resilient human population.
The Use of Modified Surrogate End Points in Cancer Clinical Trials.

The use of various surrogate end points in cancer clinical trials is erupting. Such measures reflect the efficacy of a studied intervention and may form the basis of a future approval by the United...
Lysis of virus-infected target cells by antibody-dependent cellular cytotoxicity: II. Reversibility of the heat inactivation of K cell killing and relationship of Fc receptor capping to lysis

Abstract The heat inactivation of human blood mononuclear cells active in antibody-dependent cellular cytotoxicity (ADCC) is largely reversed after 24 hr in culture at 37 °C. The reactivation process is inhibited by actinomycin D, cycloheximide, and emetine but not by mitomycin-C, indicating that recovery requires RNA and protein synthesis but not DNA synthesis. The ability of lymphocytes to cap surface immunoglobulin (SIg) and IgG-Fc receptors (FcR) was also studied. As with ADCC effector cell activity, both SIg and FcR capping were abolished by heating, and the kinetics of inactivation was similar to that of the inactivation of ADCC effector activity. In addition, the heat inactivation of capping was reversible in culture and followed kinetics of reactivation similar to that of K cell reactivation. These results suggest the participation of heat-labile proteins at or near the surface of the effector cell, which are also apparently involved in the capping of surface receptors. Presumably these heat-labile proteins are membrane-associated enzymes, but they may also be cytoskeletal structures such as microfilaments or microtubules whose heat-sensitivity is currently unknown. The mounting of lethal hits may involve the same membrane machinery which is responsible for capping or a capping process itself.
Variations in the susceptibility to Coxsackievirus B3-induced myocarditis among different strains of mice.

This study was undertaken to examine the inherent predisposition of different inbred strains of mice to develop Coxsackievirus B3-induced myocarditis. A time course study established the pertinent, differential parameters of the disease and their corresponding genetic control. The A.BY/SnJ (H-2b), A.SW/SnJ (H-2s), A.CA/SnJ (H-2f), B10.S/SgSf (H-2s), B10.PL/SgSf (H-2u), and C3H.NB/SnJ (H-2p) strains were found to vary widely in the extent and duration of viremia, in the temporal appearance and titer of neutralizing antibody, and in the prevalence, severity, and duration of myocardial disease. The A.BY/SnJ (H-2b), A.SW/SnJ (H-2s), A.CA/SnJ (H-2f), and C3H.NB/SnJ (H-2p) mice developed continuing, chronic myocardial disease, whereas B10.S/SgSf (H-2s) and B10.PL/SgSf (H-2u) did not. The four strains that displayed prolonged myocarditis also produced heart-specific myocardial autoantibodies. Heart-specific autoantibodies were not found in the B10.S/SgSf and B10.PL/SgSf animals. Differences in prevalence and titer of these heart-specific autoantibodies were noted among the three A strain H-2 congenic lines. The influence of the major histocompatibility complex (MHC) on disease production was demonstrated by comparison of the three A strain and two B10 strain H-2 congenics. Differences between A.SW/SnJ (H-2s) and B10.S/SgSf (H-2s) suggested non-MHC control of disease. These studies additionally indicate that the genetic regulation of susceptibility to CB3 infection and the direct virus-induced inflammation differ from the later immunopathic myocarditis.
Hybrid consensus-based formation control of agents with second order dynamics

In this paper, a novel hybrid consensus based formation controller is designed for agents moving in the x-y plane to drive them to a goal point while maintaining a specified formation. The proposed hybrid automaton consists of two discrete states, each with continuous dynamics: a regulation state and a formation keeping state. The controller in the regulation state is designed to drive the agent to a goal position while the formation keeping controller ensures that the agents achieve a specified geometric formation prior to reaching their goalposition. The proposed controller creates hybrid dynamics from the interactions between the continuous and discrete states. The analysis and design of hybrid systems is generally more difficult than that of purely discrete or purely continuous systems since the discrete dynamics may affect the continuous evolution and vice versa. Therefore, the stability of the hybrid approach is proven by using multiple Lyapunov functions and also considers the switching conditions between the regulation and the formation states. The Lyapunov based approach demonstrates that the formation errors converge to a small bounded region around the origin and the size of the bound can be adjusted by using the switching conditions. Convergence to goal position while in formation is also demonstrated in the same Lyapunov analysis, and simulation results verify the theoretical conjectures.
The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein.

Abstract The human papillomavirus (HPV) E5 proteins are predicted from DNA sequence analysis to be small hydrophobic molecules, and the HPV type 6 (HPV-6) and HPV-11 E5 proteins share several structural similarities with the bovine papillomavirus type 1 (BPV-1) E5 protein. Also similar to the BPV-1 E5 protein, the HPV-6 and HPV-16 E5 proteins exhibit transforming activity when assayed on NIH 3T3 and C127 cells. In this study, we expressed epitope-tagged E5 proteins from both the "low-risk" HPV-6 and the "high-risk" HPV-16 in order to permit their immunologic identification and biochemical characterization. While the HPV-6 and HPV-16 E5 proteins fail to form disulfide-linked dimers and oligomers, they did resemble the BPV-1 E5 protein in their intracellular localization to the Golgi apparatus, endoplasmic reticulum, and nuclear membranes. In addition, the HPV E5 proteins also bound to the 16-kDa pore-forming protein component of the vacuolar ATPase, a known characteristic of the BPV-1 E5 protein. These studies reveal a common intramembrane localization and potential cellular protein target for both the BPV and HPV E5 proteins.
X-ray photoemission spectroscopy study of LaCuO3.

The metallic rhombohedral (R3\ifmmode\bar\else\textasciimacron\fi{}c), perovskite ${\mathrm{LaCuO}}_{3}$ has been synthesized under a high pressure of oxygen. The Cu 2${\mathit{p}}_{3/2}$ x-ray photoemission spectroscopy (XPS) peak exhibits a shift of 2.6 eV to higher binding energy relative to that of Cu ii in CuO and ${\mathrm{La}}_{2}$${\mathrm{CuO}}_{4}$. The modified Auger parameter is of comparable magnitude in the two compounds and the ${\mathit{L}}_{3}$VV Auger-electron kinetic energy is shifted by 2.8 eV relative to that of CuO. These shifts are representative of Cu iii in an octahedral site linked to neighboring Cu iii via a single 180\ifmmode^\circ\else\textdegree\fi{} Cu-O-Cu bridge in a metallic phase. This spectrum is therefore a useful standard for comparison with the XPS spectra of the p-type high-${\mathit{T}}_{\mathit{c}}$ copper oxides. The present standard is the XPS spectrum of the insulator ${\mathrm{NaCuO}}_{2}$, which contains Cu iii in square coplanar coordination and which is bridged to neighboring Cu iii by two oxygen bridges having a Cu-O-Cu bond angle approaching 90?; its chemical shift is 1.3 eV smaller than that of metallic ${\mathrm{LaCuO}}_{3}$.
Freedom and Corporate Responsibility: The Niger Delta Case

This article briefly introduces a new argument concerning corporate social responsibility, based in an analysis of values expressed by the recent and contemporary liberal economists Milton Friedman and Michael Jensen. I will provide the gist of the argument by considering implications of Friedman’s very familiar view, that “…there is one and only one social responsibility of business - to use its resources and engage in activities to increase its profits so long as it stays within the rules of the game.” Harvard professor Michael Jensen has argued from slightly different premises to a similar conclusion, that “social welfare is maximized when all firms in an economy attempt to maximize their own total firm value.” Vestiges of such influential argument are also easily spotted in American corporate culture (See Palmer, 2007). I suggest that these authors’ positions allow for possibilities that undermine their broader fundamental values, however. I will concentate especially on Friedman’s classic treatment of liberal politics and capitalist economics, Capitalism and Freedom, in which he alludes to the importance of accepting and promoting individual freedom. Such values demand governmental and social stability, and so, in some cases, particularly where business activity may destabilize society, it would appear that freedom may be seriously threatened by corporate activity that follows Friedman’s narrow prescription. Nowhere is this more evident, at present, than in the Niger River Delta, where the promise and profits of oil have produced a society in great disarray. A case study of the delta situation indicates the problems of the narrow view of business goals and business responsibility, and this article will go on to consider possible solutions to those problems that delineate general sorts of responsibilities. The solutions require corporations to take a much broader view of their activity: I suggest that Friedman’s flaw reflects a general weakness of liberal individualism, nicely exposed in Amartya Sen’s arguments that lead to the conclusion that, “we have to see individual freedom as a social commitment.” That social commitment includes the goal of promoting individual freedom, but reaching for the goal may proceed along lines that are not so narrowly economic as Friedman would have, indicating new roles for business and government cooperation even in less extreme cases than that of the Niger Delta.
A native interactor scaffolds and stabilizes toxic ATAXIN-1 oligomers in SCA1

Recent studies indicate that soluble oligomers drive pathogenesis in several neurodegenerative proteinopathies, including Alzheimer and Parkinson disease. Curiously, the same conformational antibody recognizes different disease-related oligomers, despite the variations in clinical presentation and brain regions affected, suggesting that the oligomer structure might be responsible for toxicity. We investigated whether polyglutamine-expanded ATAXIN-1, the protein that underlies spinocerebellar ataxia type 1, forms toxic oligomers and, if so, what underlies their toxicity. We found that mutant ATXN1 does form oligomers and that oligomer levels correlate with disease progression in the Atxn1(154Q/+) mice. Moreover, oligomeric toxicity, stabilization and seeding require interaction with Capicua, which is expressed at greater ratios with respect to ATXN1 in the cerebellum than in less vulnerable brain regions. Thus, specific interactors, not merely oligomeric structure, drive pathogenesis and contribute to regional vulnerability. Identifying interactors that stabilize toxic oligomeric complexes could answer longstanding questions about the pathogenesis of other proteinopathies.
Introduction Studies in Captive Wolf Packs

Zusammenfassung Ein- und dreijahrige Wolfe verschiedenen Ranges und verschiedenen Geschlechts wurden in den Heimatzwinger eines oder mehrerer zweijahriger Wolfe von bekanntem Rang eingefuhrt. Ebenso wurde umgekehrt ein ortsansassiger Testwolf in einen fremden Zwinger gebracht. Hochrangige ortsansassige Wolfe waren aggressiver den Fremden gegenuber als die rangniederen; das heimische Alpha-♂ war am aggressivsten Fremden gegenuber (sogar im Heimzwinger der Letztgenannten); als sie mit dem Alpha-♂ ihres Rudels gepaart wurde, neigte sie dazu, dessen Aggression gegen Fremde anzuregen. Einjahrige Wolfe zeigten mehr Furcht und Verteidigung als dreijahrige, einige der dreijahrigen zeigten angriffshemmende “passive Gleichgultigkeit”. Mannliche und weibliche einjahrige α-Tiere waren in Anwesenheit eines alten Leitwolfes in ihrem Heimatzwinger den zweijahrigen gegenuber dominant, doch alleine im Zwinger der Zweijahrigen waren sie unterlegen. Es ist moglich, das zwei getrennte Gruppen oder Rudel sich zusammenschliesen, weil beide eine soziale Bindung zu einem alteren Wolf haben.
Solving the all-pair shortest path problem on interval and circular-arc graphs

We show that, given the interval model of an unweighted n-vertex interval graph, the information for the all-pair shortest paths can be made available very efficiently, both in parallel and sequentially. After sorting the input intervals by their endpoints, an O(n) space data structure can be constructed optimally in parallel, in O(log n) time using O(n/log n) CREW PRAM processors. Using the data structure, a query on the length of the shortest path between any two input intervals can be answered in O(1) time using one processor, and a query on the actual shortest path can be answered in O(1) time using k processors, where k is the number of intervals on that path. Our parallel algorithm immediately implies a new sequential result: After an O(n) time preprocess, shortest paths can be reported optimally. Our techniques can be extended to solve the problem on circular-arc graphs, both in parallel and sequentially, in the same complexity bounds. The previously best known sequential algorithm for computing the all-pair shortest paths in interval graphs lakes O(n/sup 2/) time and uses O(n/sup 2/) space to store the lengths of the all-pair shortest paths. >
The binding of estrogens in the liver of the rat: Demonstration and endocrine influences

Abstract The existence of an estrophilic macromolecule in the cytoplasm of rat liver is established, and some of its characteristics are examined by use of a Dextran-coated charcoal assay under conditions which minimize metabolism. The estrophile sediments at 4–5 s with aggregates of 8–9 s in either Tris-EDTA or Tris-magnesium buffer. The best resolution is achieved in magnesium buffers at high ionic strength. Estrogens bind to this protein with high association constants ( K a , for estradiol = 6.0 × 10 9 M −1 ) whereas androgens and glucocorticoids bind much less firmly. In experiments designed to examine the effect of various hormonal manipulations on the concentration of this estrophile in liver, the following observations were made: (1) There is no effect of 5μg estradiol-benzoate in intact females; (2) Ovariectomy causes a 2–3 fold increase in capacity which decreases significantly, but not to control values, after the administration of 5 μg estradiol-benzoate; (3) Hypophysectomy causes a 5-fold decrease in capacity.
Role of F‐actin in Thermal Gelation of Fish Actomyosin

The thermal gelation processes of the myosin-natural actomyosin system were investigated to determine the role of F-actin in thermal gelation of actomyosin. The dynamic viscoelastic behavior during thermal gelation changed considerably depending on the (F-actin)/ (myosin) ratio. F-actin gave the viscosity to an actomyosin sol but did not affect the elasticity development occurring in the 30 - 46°C range. The decrease in storage modulus in the 46 - 53°C range was directly induced by the presence of F-actin. The gel of myosin alone showed the highest elasticity, while that of myosin containing a small amount of F-actin had the highest elastic modulus.
PKC‐α shows variable patterns of translocation in response to different stimulatory agents

Reports from numerous laboratories suggest that protein kinase C (PKC) translocation to substrate target sites may vary depending on cell type and experimental conditions. We have proposed that acutely variable targeting of PKC to different substrate sites could greatly expand the functional properties of individual isoforms in individual cell types (Li et al., 2001). Confocal microscopy and PKC alpha-enhanced green fluorescent protein (PKC alpha-EGFP) fusion protein expression were utilized to investigate the spatial and temporal pattern of PKC alpha translocation to different stimulating agents in A7r5 smooth muscle cells. Phorbol 12, 13 dibutyrate (PDBu 10(-8) M) caused a slow but irreversible relocation of the fusion protein from the cytosol to the plasmalemma. By comparison, thapsigargin (10(-5) M) and A23 187 (2 x 10(-5) M) induced a rapidly transient translocation to the cell membrane which was completed within 4 min. In contrast to these agents, angiotensin II (Ang II, 10(-6) M) caused only partial relocalization of cytosolic PKC alpha-EGFP to brightly fluorescing patches at the cell periphery. Localization at peripheral patches was completed within seconds and the fusion protein returned to the cytosol within 2 min. The PKC inhibitor staurosporine blocked cellular contraction to PDBu but not A(23 187) and had no effect on PKC alpha-EGFP translocation. By comparison, the calcium chelators EDTA and BAPTA-AM blocked the contraction to A(23 187), attenuated the contraction to PDBu, and abolished the translocation of PKC alpha-EGFP by both agents. The results show that in a single cell type the spatial and temporal characteristics of individual PKC isoform translocation may differ markedly. This further suggests the existence of potentially complex mechanisms which regulate the rate and location of target site availability.
Mineralization induction effects of osteopontin, bone sialoprotein, and dentin phosphoprotein on a biomimetic collagen substrate

Native bone tissue is composed of a matrix of collagen, noncollagenous proteins, and calcium phosphate minerals, which are primarily hydroxyapatite. The SIBLING (small integrin-binding ligand, N-linked glycoprotein) family of proteins is the primary noncollagenous protein group found in mineralized tissues. In this work, the mineralization induction capabilities of three of the SIBLING members, bone sialoprotein (BSP), osteopontin (OPN), and the calcium-binding subdomain of dentin sialophosphoprotein, dentin phosphoprotein (DPP), are directly compared on a biomimetic collagen substrate. A self-assembled, loosely aligned collagen fibril substrate was prepared, and then (125) I-radiolabeled adsorption isotherms were developed for BSP, OPN, and DPP. The results showed that BSP exhibited the highest binding capacity for collagen at lower concentrations, followed by DPP and OPN. However, at the highest concentrations, all three proteins had similar adsorption levels. The adsorption isotherms were then used to identify conditions that resulted in identical amounts of adsorbed protein. These substrates were prepared and placed in simulated body fluid for 5, 10, and 24 h at 37°C. The resulting mineral morphology was assessed by atomic force microscopy, and the composition was determined using photochemical assays. Mineralization was seen in the presence of all the proteins. However, DPP was seen to be the only protein that formed individual mineral nodules similar to those seen in developing bone. This suggests that DPP plays a significant role in the biomineralization process and that the incorporation of DPP into tissue engineering constructs may facilitate the induction of biomimetic mineral formation.
Olanzapine transfer by human placenta.

SUMMARY 1. The present study assessed the human transplacental transport of olanzapine, a new antipsychotic drug effective in the treatment of schizophrenia. 2. Using the normal-term placenta perfused single cotyledon system, we show that: (i) 5–14% of labelled olanzapine crosses from the maternal to foetal compartments in 4 h; (ii) transport depends significantly on binding characteristics, especially of albumin; (iii) no oxidative metabolites of olanzapine appear in the placental perfusate over 4 h; and (iv) approximately 17% of olanzapine, on average, is converted to the glucuronide, which is transferred by the placenta at a rate slightly slower than the parent drug.
THE STOCHASTIC MODEL OF MENTAL TESTING THEORY AND AN APPLICATION

An axiomatization of mental test theory is presented. The presentation deals explicitly with the following concepts: true score, parallel forms, reliability, validity, and combined test score.
The N.M.R. spectra of some bicyclo [2.2.1] heptanols

The high-resolution N.M.R. spectra of a series of bicyclo [2.2.1] heptanols are discussed. Three unusual features are observed: (a) relatively large 4 J's; (b) unequal J endo-endo's and J exo-exo's; and (c) unusual magnetic shieldings. These are presented as empirical phenomena and only little attempt is made to discuss their implications.
Interference effects in the quasimolecular K x-ray production probability for 10-MeV Cl/sup 16 +/-Ar collisions

The impact-parameter dependence of the quasimolecular $K$ x rays emitted in collisions of 10-MeV ${\mathrm{Cl}}^{16+}$ with Ar has been measured. The coincidence spectra show a clear impact-parameter-dependent structure. The results are in good agreement with dynamical calculations which take into account the interference between the $1s\ensuremath{\sigma}$ decay amplitudes in the incoming and the outgoing halves of the trajectory.
Filled elastomers: A theory of filler reinforcement based on hydrodynamic and interphasial effects

Abstract Experimental evidence has by now established that (i) the hydrodynamic effect and (ii) the presence of stiff interphases (commonly referred to as bound rubber) “bonding” the underlying elastomer to the fillers are the dominant microscopic mechanisms typically responsible for the enhanced macroscopic stiffness of filled elastomers. Yet, because of the technical difficulties of dealing with these fine-scale effects within the realm of finite deformations, the theoretical reproduction of the macroscopic mechanical response of filled elastomers has remained an open problem. The object of this paper is to put forward a microscopic field theory with the capability to describe, explain, and predict the macroscopic response of filled elastomers under arbitrarily large nonlinear elastic deformations directly in terms of: (i) the nonlinear elastic properties of the elastomeric matrix, (ii) the concentration of filler particles, and (iii) the thickness and stiffness of the surrounding interphases. Attention is restricted to the prominent case of isotropic incompressible elastomers filled with a random and isotropic distribution of comparatively rigid fillers. The central idea of the theory rests on the construction of a homogenization solution for the fundamental problem of a Gaussian elastomer filled with a dilute concentration of rigid spherical particles bonded through Gaussian interphases of constant thickness, and on the extension of this solution to non-Gaussian elastomers filled with finite concentrations of particles and interphases by means of a combination of iterative and variational techniques. For demonstration purposes, the theory is compared with full 3D finite-element simulations of the large-deformation response of Gaussian and non-Gaussian elastomers reinforced by isotropic distributions of rigid spherical particles bonded through interphases of various finite sizes and stiffnesses, as well as with experimental data available from the literature. Good agreement is found in all of these comparisons. The implications of this agreement are discussed.
T-cell deficiency in immune complex glomerulonephritis

T-cell deficiency in immune complex glomerulonephritis. Mice chronically infected with the virus of lymphocytic choriomeningitis (LCM) develop immune complex glomerulonephritis. Others have shown that adoptive immunization of these mice by the i.p. injection of syngeneic immune spleen cells terminates the chronic viral carrier state. The present studies were designed to define the effector cell from the immune spleen responsible for adoptive immunization and to determine the effect of this procedure upon the immune complex nephritis which occurs in LCM carrier mice. The results indicate that the effector cell in adoptive immunization is a T-cell that functions directly as a killer cell when transferred to LCM carrier mice. Sixteen of nineteen adoptively immunized mice examined had less immune complex material deposited in their glomeruli than control unmanipulated litter mates. These data demonstrate that this animal model of immune complex glomerulonephritis is immunodeficient with respect to LCM virus-specific killer T-cells. Transfer of this cell population to the LCM carrier mouse diminishes the animal's viremia and improves its immune complex nephritis. In view of these observations, it is suggested that the rationale for the use of immunosuppressive therapy in spontaneously occurring glomerulonephritis should be carefully reconsidered. Deficit des lymphocytes T dans la glomerulonephrite des complexes immuns. Les souris infectees de facon chronique par le virus de la choriomeningite lymphocytaire (LCM) developpent une glomerulonephrite des complexes immuns. D'autres auteurs ont montre que l'immunisation passive de ces souris par l'injection intraperitoneale de cellules spleniques syngeniques immunes met un terme a l'etat de porteur chronique du virus. Les experiences rapportees ont eu pour but de definir la cellule effectrice de la rate immune responsable de l'immunisation passive et de determiner l'effet de cette immunisation sur la nephrite des complexes immuns qui survient chez la souris porteuse du virus LCM. Les resultats indiquent que la cellule effectrice dans l'immunisation passive est un lymphocyte T qui fonctionne directement comme une cellule K quand il est transfere a une souris porteuse de LCM. Onze parmi les quatorze souris ayant subi l'immunisation avaient moins de complexes immuns deposes dans les glomerules que les animaux de la meme portee non traites. Ces resultats montrent que ce modele animal de glomerulonephrite des complexes immuns est immunologiquement deficitaire en ce qui concerne les cellules K specifiques du virus LCM. Le transfert de cette population cellulaire a la souris porteuse du virus LCM diminue la viremie de l'animal et ameliore sa nephrite des immuns complexes. En fonction de ces observations il est suggere que les bases logiques de l'emploi d'immunosuppresseurs dans les glomerulonephrites de survenue spontanee soient soigneusement reconsiderees.
The effect of Ac dosage on the production of multiple forms of Wx protein by the wx m-9 controlling element mutation in maize

Summary. The WX m-9 autonomous controlling element mutation produces either a single or doublet type protein in 20 day endosperm, depending on the dosage of Ac. The single protein observed in one dose Ac endosperm is the product of wx m-9 to Wx revertants. The doublet observed in two and three dose Ac endosperm is the product of the Ac-containing, partially suppressed wx "-9 gene. Mutual exclusion of the activities of the wx m-9 gene and its included Ac element is postulated. A competition model is presented to account for the unexpected Ac dosage effect. One approach to the analysis of the Ac-Ds transposable controlling element system in maize is the comparison of the protein product of a gene suppressed by the controlling element with that of the unsuppressed gene (Hannah and Nelson 1976; Dooner and Nelson 1977). The Wx locus is especially well suited for such studies. This gene specifies a starch-bound glycosyl transferase which is responsible for the production of amylose in the endosperm and pollen (Nelson and Rines 1962; Tsai 1974). Gene activity can be analyzed at the enzymatic, phenotypic, and protein levels. The wx mutants m-l, m-6, and B4, mapped by Nelson (1968, 76), where a controlling element is inserted in the Wx gene, cannot be analyzed by this approach since they represent cases of complete gene suppression and no detectable gene product is produced (Echt and Schwartz 1981). The autonomous wx m-9 mutation, hereafter designated m-9, has an Ac controlling element at the Wx locus (McClintock 1963). This mutant only partially suppresses the activity of the Wx gene since the endosperm stains pale blue with iodine, indicative of the presence of a low amount of amylose. The m-9 mutant undergoes frequent reversions to Wx as well as mutations to a stable recessive wx allele which does not make amylose. This paper deals with an analysis of the proteins produced by the suppressed and revertant m-9 mutant. Evidence will be presented which suggests that Ac is located within the limits of the coding region of the Wx gene where it behaves as an intron in that its sequence is not represented in the protein specified by the m-9 gene.
Brightness acuity test and outdoor visual acuity in cataract patients.

The disparity between functional outdoor vision and the acuity measured in the standard refracting lane is well known among clinicians. A simple device, the brightness acuity tester (B.A.T.), was developed to predict a patient's functional outdoor acuity. The B.A.T. has an illuminated hemispheric bowl, 60 mm in diameter, with a 12-mm aperture. Fourteen normals and 50 patients with cataracts were tested using the B.A.T. and then tested outside in bright sunlight. The B.A.T. correlated extremely well (r = +0.84, P less than .0001) with the acuities measured outside. There was no decrease in visual acuity in the 14 normal patients, but there was a one to ten line decrease in vision among the cataract patients. Upon retesting, the B.A.T. scores did not vary, while outside testing scores did change due to variable outdoor ambient light levels on sunny days. The B.A.T. is a simple, repeatable, useful test for predicting functional outdoor acuity.
Some descriptive aspects of two-person non-zero-sum games. II

1 This research was supported in whole by the United States Air Force under Contract No. AF 49(638)-317 monitored by the Air Force Office of Scientific Research of the Air Research and Development Command. as s ported in whole by the It is to be noted that in G-type games a2 dominates a, and p2 dominates pi, and, hence, the outcome (a2, /82) may appear to be the rational joint choice. On the other hand, the outcome (al, /i) has a larger joint payoff than any other; further, since x1 > X4, the outcome (ai, /1) has a larger individual payoff than that associated with (a2, P/2). We regard (ac, P/) as the collaborative strategy, since only in this way may subjects maximize their return. Whether or not one may reasonably expect pairs of subjects to collaborate with one another is an open question. However, in an iterated version of such a game there are strong intuitive grounds for expecting the emergence of a collaborative strategy, especially when the number of trials becomes large.4 The specific game employed in the paper mentioned above is given by xl = 3, x2 = 0, xa = 5, and x4 = 1. Actually, three versions of this game, G1, G2, and G3, were used. The results reported in this paper have to do with three additional G-type games and with four non-G-type games. The non-Gtype games have the same general payoff
Enhancement of opioid-mediated analgesia: A solution to the enigma of placentophagia

Two major consequences of placentophagia, the ingestion of afterbirth materials that occurs usually during mammalian parturition, have been uncovered in the past several years. The first is that increased contact, associated with ingesting placenta and amniotic fluid from the surface of the young, causes an accelerated onset of maternal behavior toward those young. The second, which probably has importance for a broader range of mammalian taxa than the first, is that ingestion of afterbirth materials produces enhancement of ongoing opioid-mediated analgesia. The active substance in placenta and amniotic fluid has been named POEF, for Placental Opioid-Enhancing Factor. Recent research on both consequences is summarized, with particular attention to POEF, the generalizability of the enhancement phenomenon, its locus and mode of action, and its significance for new approaches to the management of pain and addiction.
Promoting Research as a Core Value in Master's-Level Counselor Education

Theory, practice, and research are all espoused to be core values within counselor education. The authors assert that research needs to become directly associated with theory and practice for it to be a concurrent core value. Action research is most simply defined as a form of research that is practitioner based. The authors propose infusing action research throughout master's-level curricula as a means of promoting research as a core value concurrent with theory and practice. A case illustration of an action research investigation in a Professional and Ethical Issues in Mental Health Counseling course is described.
Effect of severe calorie restriction on the lung in two strains of mice.

There is a body of literature in animal models that has suggested the development of emphysema following severe calorie restriction. This has led to the notion of “nutritional emphysema” that might have relevance in COPD patients. There have been few studies, however, that have looked closely at both the mechanics and lung structure in the same animals. In the present work, we examined lung mechanics and histological changes in two strains of mice that have substantial differences in alveolar size, the C57BL/6 and C3H/HeJ strains. We quantified the dynamic elastance and resistance at 2.5 Hz, the quasistatic pressure volume curve, and the alveolar chord lengths in lungs inflated to a lung capacity at 25–30 cmH2O. We found that after 2 or 3 wk of calorie restriction to 1/3 their normal diet, the lungs became stiffer with increased resistance. In addition, the lung capacity was also decreased. These mechanical changes were reversed after 2 wk on a normal ad libitum diet. Histology of the postmortem fixed lungs showed no changes in the mean alveolar chord lengths with calorie restriction. Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size, neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult.