cssi/SciSciGPT-SciSciNet huggingface dataset:
Prosocial effects of an oxytocin metabolite, but not synthetic oxytocin receptor agonists, in a mouse model of autism

Abstract Currently, there are no established pharmaceutical strategies that effectively treat social deficits in autism spectrum disorder (ASD). Oxytocin, a neurohormone that plays a role in multiple types of social behaviors, has been proposed as a possible therapeutic against social impairment and other symptoms in ASD. However, from the standpoint of pharmacotherapy, oxytocin has several liabilities as a standard clinical treatment, including rapid metabolism, low brain penetrance, and activity at the vasopressin (antidiuretic hormone) receptors. The present studies describe findings from a preclinical screening program to evaluate oxytocin receptor (OXTR) agonists and oxytocin metabolites for potential clinical use as more optimal treatments. We first investigated two synthetic oxytocin analogs, TC-OT-39 and carbetocin, using in vitro cell-based assays for pharmacological characterization and behavioral tests in the BALB/cByJ mouse model of ASD-like social deficits. Although both TC-OT-39 and carbetocin selectively activate the OXTR, neither synthetic agonist had prosocial efficacy in the BALB/cByJ model. We next evaluated two oxytocin metabolites: OT(4–9) and OT(5–9). While OT(5–9) failed to affect social deficits, the metabolite OT(4–9) led to significant social preference in the BALB/cByJ model, in a dose-dependent manner. The increased sociability was observed at both 24 h and 12 days following the end of a subchronic regimen with OT(4–9) (2.0 mg/kg). Overall, these results suggest that the prosocial effects of oxytocin could be mediated by downstream activity of oxytocin metabolites, raising the possibility of new pathways to target for drug discovery relevant to ASD.
Anthropogenic stresses on the world’s big rivers

The world’s big rivers and their floodplains were central to development of civilization and are now home to c. 2.7 billion people. They are economically vital whilst also constituting some of the most diverse habitats on Earth. However, a number of anthropogenic stressors, including large-scale damming, hydrological change, pollution, introduction of non-native species and sediment mining, challenge their integrity and future, as never before. The rapidity and extent of such change is so great that large-scale, and potentially irreparable, transformations may ensue in periods of years to decades, with ecosystem collapse being possible in some big rivers. Prioritizing the fate of the world’s great river corridors on an international political stage is imperative. Future sustainable management, and establishment of environmental flow requirements for the world’s big rivers, must be supported through co-ordinated international funding, and trans-continental political agreement to monitor these rivers, finance their continual upkeep and help ameliorate increasing anthropogenic pressures. To have any effect, all of these must be set within an inclusive governance framework across scales, organizations and local populace. Stressors such as large-scale damming, hydrological change, pollution, the introduction of non-native species and sediment mining are challenging the integrity and future of large rivers, according to a synthesis of the literature on the 32 biggest rivers.
Soft Tissue Neck Injury

Soft tissue neck injuries in sports do not occur infrequently. They usually occur with high-velocity trauma and in contact sports. Most injuries are due to blunt neck trauma, but penetrating injury is also possible. The most common neck injury is the usually benign cervical strain. However, more severe injuries may occur due to the presence of vascular, digestive, and airway structures located in the neck. It is important to be able to recognize the signs and symptoms suggestive of more serious injury and know how to stabilize them, as they can quickly become life-threatening.
Syndecan-1 Is a Multifunctional Regulator of Myeloma Pathobiology: Control of Tumor Cell Survival, Growth, and Bone Cell Differentiation

Multiple myeloma is characterized by an accumulation of malignant plasma cells in the bone marrow coupled with an altered balance of osteoclasts and osteoblasts, leading to lytic bone disease. Although some of the cytokines driving this process have been characterized, little is known about the negative regulators. We show that syndecan-1 (CD 138), a heparan sulfate proteoglycan, expressed on and actively shed from the surface of most myeloma cells, induces apoptosis and inhibits the growth of myeloma tumor cells and also mediates decreased osteoclast and increased osteoblast differentiation. The addition of intact purified syndecan-1 ectodomain (1 to 6 nmol/L) to myeloma cell lines in culture leads to induction of apoptosis and dose-dependent growth inhibition, with concurrent downregulation of cyclin D1. The addition of purified syndecan-1 in picomolar concentrations to bone marrow cells in culture leads to a dose-dependent decrease in osteoclastogenesis and a smaller increase in osteoblastogenesis. In contrast to the effect on myeloma cells, the effect of syndecan-1 on osteoclastogenesis only requires the syndecan-1 heparan sulfate chains and not the intact ectodomain, suggesting that syndecan's effect on myeloma and bone cells occurs through different mechanisms. When injected in severe combined immune deficient (scid) mice, control-transfected myeloma cells (ARH-77 cells) expressing little syndecan-1 readily form tumors, leading to hind limb paralysis and lytic bone disease. However, after the injection of syndecan-1-transfected ARH-77 cells, the development of disease-related morbidity and lytic bone disease is significantly inhibited. Taken together, our data demonstrate, both in vitro and in vivo, that syndecan-1 has a significant beneficial effect on the behavior of both myeloma and bone cells and therefore may represent one of the central molecules in the regulation of myeloma pathobiology.
A comparative analysis of interferons and direct-acting antivirals on the expression of genes involved in hepatitis C pathogenesis.

The discovery of direct-acting antivirals (DAAs) has revolutionized the treatment of hepatitis C worldwide. In contrast, pegylated interferon-alpha (PEG IFN-α), the older regimen, had limited success. However, the effect of DAAs on the expression of immunomodulatory genes involved in liver pathologies remains ambiguous. The objective of this study was to explore and contrast the effects of DAAs and PEG IFN-α on the expression of selected immunomodulatory genes. Fifty individuals were enrolled in the study and they were divided into five categories; healthy individuals, treatment-naive, DAAs-responders, DAAs-nonresponders, and interferon-relapsers. The effect of the therapies on the expression of transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), suppressor of cytokine signaling 3 (SOCS-3), copper/zinc superoxide dismutase (Cu/Zn SOD), interleukin 10 (IL-10), and collagen type 1 was analyzed. Expression analysis of the selected genes was done through real time PCR. A significantly increased expression of TGF-β was observed in the patients who received DAAs or PEG IFN-α, which suggests that patients receiving anti-HCV therapies are prone to developing fibrosis. Moreover, DAAs-nonresponders had higher expression of TNF-α, SOCS-3, and IL-10. The elevated expression of TNF-α and SOCS-3 insinuates that DAAs-nonresponders may develop insulin resistance and steatosis in the future. Finally, in addition to TGF-β, high expression of collagen was found in interferon relapsers, which suggests that these patients are the most susceptible to developing cirrhosis. This article is protected by copyright. All rights reserved.
SR3: Customizable Recovery for Stateful Stream Processing Systems

Modern stream processing applications need to store and update state along with their processing, and process live data streams in a timely fashion from massive and geo-distributed data sets. Since they run in a dynamic distributed environment and their workloads may change in unexpected ways, multiple stream operators can fail at the same time, causing severe state loss. However, the state-of-the-art stream processing systems are mainly designed for low-latency intra-datacenter settings and do not scale well for running stream applications that contain large distributed states, suffering a significantly centralized bottleneck and high latency to recover state. They offer failure recovery mainly through three approaches: replication recovery, checkpointing recovery, and DStream-based lineage recovery, which are either slow, resource-expensive or fail to handle multiple simultaneous failures. We present SR3, a customizable state recovery framework that provides fast and scalable state recovery mechanisms for protecting large distributed states in stream processing systems. SR3 offers three recovery mechanisms --- the star-structured recovery, the line-structured recovery, and the tree-structured recovery --- to cater to the needs of different stream processing computation models, state sizes, and network settings. Our design adopts a decentralized architecture that partitions and replicates states by using consistent ring overlays that leverage distributed hash tables (DHTs). We show that this approach can significantly improve the scalability and flexibility of state recovery. We realize the SR3 design on a prototype integrated with the widely adopted Apache Storm framework. Large-scale experiments using real-world datasets demonstrate SR3's scalability, fast recovery, and flexibility properties.
Visualizing the teaching of data visualizations in social studies: A study of teachers’ data literacy practices, beliefs, and knowledge

Data literacy—the ability to comprehend, analyze, and interpret data and data visualizations—is inextricably linked to the goals of K–12 social studies education. In a society where data visualizat...
Host Adaptations of the Salmonella Typhi Typhoid Toxin and Its Orthologue from a Nontyphoidal Salmonella

Typhoidal and nontyphoidal Salmonellae (NTS) cause typhoid fever and gastroenteritis respectively in humans. Typhoid toxin from typhoidal Salmonella contributes to typhoid disease progression and chronic infection, but little is known about its orthologue from NTS. We found that these two Salmonella toxins do not cause similar toxicities in vivo. The altered virulence outcomes are due to the altered glycan binding preferences of these two toxins, which are correlated to the glycan expression profiles of target host cells at the primary infection or intoxication sites of their associated bacteria. The co-crystal structures of the glycan-receptor binding PltB subunits of the toxins bound to specific glycan receptor moieties explain how PltBs of these two toxins display markedly different glycan binding preferences and contribute to the subsequent virulence outcomes. We also revealed that administration of either Javiana toxin or S. Javiana into an animal model provides cross-reactive protection for typhoid-related illnesses and mortality.
A Process Mining Approach for Resource Allocation Management in a Bike Sharing System

Bike Sharing System (BSS), an alternative transportation option in big cities worldwide, improves urban mobility in such a way as to meet efficiently the needs of citizens while at the same time being beneficial to the environment. A major challenge for BSS operators is the optimal resource allocation so as to have a full-time, flexible and operational system. Due to the multi-dimensional nature of the problem, an overall view of the system and a deep analysis are required. To our knowledge, no research has been conducted to date on taking a process mining view on BSS. The main idea and the scope of this paper is to analyze BSS as a process and employ process mining techniques to provide multi-perspective analysis and answer questions about the structure and operation of the system, so as to contribute to the optimal resource allocation management. From the analysis, it is shown that visual representations and animations can contribute to a better understanding of the functioning of the system and to the optimization of decision making.
Exercise 27: Immunoprecipitation

Antibodies or immunoglobulin binding proteins immobilized on sepharose or agarose beads can be used to bind immune complexes formed by antibody binding to antigen usually contained in an extract. The purified antigen is solubilized by boiling the beads in sample buffer. This process of pulling out a specific protein from a heterogeneous mixture of proteins from a cell extract is known as immunoprecipitation. The immunoglobulin binding proteins can be incubated with antibodies first, then incubated with the protein extract to pull out the specific protein from the extract. This is useful when antibody concentration is low. The antibody specific for the antigen is used to purify the protein out if the extract. Antibody may also be incubated with the cell extract to form the immune complex. Antibody or protein A immobilized beads may then be added to the antibody-antigen reaction, to pull out the immune complex. Proteins A, G and L are immunoglobulin binding proteins used for immunoprecipitation assays. Protein A is a 42 kDa surface protein produced by some strains of Staphylococcus aureus. Protein A binds to the Fc region of IgG. Protein G is produced by group C and G Streptococcus as a 58 and 65 kDa, protein respectively. Protein G also binds to the Fc region of IgG. Recombinant proteins containing protein A and G are also used for immunoprecipitation. Protein L is produced by Peptostreptococcus magnus, and is a 76 kDa protein that also bind immunoglobulin but binds to the light chain region of the molecule, specifically to kappa light chains. The immunoprecipitation assay is the basis for pull-down assays used to identify proteins in cell signaling pathways, identifying interacting protein partners in protein-protein I nteractions and in identifying DNA binding proteins in chromatin immunoprecipitation (ChIP). Immunoprecipitation assays are important in pulse chase experiments employing biosynthetically (35S-methionine) labeled proteins. The objective of this exercise is to learn how to perform the immunoprecipitation assay.
Beyond the Standard Model Searches with the Majorana Demonstrator Experiment

The Majorana Demonstrator experiment operated two modular arrays of p-type point contact high purity germanium (HPGe) detectors, of which 30 kg is enriched to 88% in Ge-76, to search for neutrinoless double beta decay. The data-taking campaign for double beta decay with enriched detectors was successfully concluded in March 2021, and data-taking with natural detectors is still ongoing. The Demonstrator has achieved excellent energy performance in a wide dynamic range covering 1 keV to 10 MeV. The extra-low background level and excellent energy performance achieved by the Demonstrator makes it competitive in various searches of physics beyond the Standard Model. If there is an axion-photon coupling, axions can be produced by the Primakoff conversion of photons in the Sun. Solar axions can inversely generate photon signals in germanium crystals, which can be coherently enhanced when the Bragg condition is satisfied. The Demonstrator is searching for solar axions with a novel method to correlate and leverage its high number of HPGe detectors. In this talk, we will discuss the status and results of recent searches for new physics with the Demonstrator, including the first reporting of a solar axion search.
On the Generalized Nonlinear Fuzzy Variational Inclusions

In this paper, a new generalized nonlinear fuzzy variational inclusion in real Hilbert space is introduced. Using the auxiliary principle technique, a iterative algorithm to compute the approximate solution is constructed, and the convergence criteria is proved under some mild conditions.
Viruses, Genes, and Cancer: a Lineage of Discovery

Genetic dowries contain two sorts of genes that govern the proliferation of cells: one sort provides accelerators to activate the engines of the cell, and the other sort provides brakes. In this chapter, the author briefly narrates a story rich with illustrations of how science proceeds, of what it can and cannot do. It is a story that can be accessible by even the most general reader. It is a story that does great credit to the legacy of Howard Temin. The story begins with cells, those microscopic, irreducible, living bricks from which bodies are constructed. The ability of cells to multiply lies at the root of life, but it also prefigures the baleful threat of cancer. Giant strides were made to view cancer as a disease of individual cells and to study this disease not in an animal but in a petri dish, and also to exploit viruses that rapidly and reproducibly convert cells to cancerous growth. Bodies are divided into two lineages one lineage, the somatic lineage (from "soma," for body), and another lineage, the germinal lineage or germ line. Most cancer genes arise from damage in the somatic lineage and thus affect only a single individual. The discovery and exploration of proto-oncogenes provided a new view of the cancer cell, rich in detail and prospect.
Critical involvement of GPCR kinase-5 in E.coli induced pneumonia (INC7P.427)

G-protein coupled receptor kinases are serine/threonine kinases involved in a range of pathophysiological processes including inflammation. We recently demonstrated, deficiency of G-protein coupled receptor kinase-5 (GRK5) improves sepsis outcome in a polymicrobial septic. In this study we examined the role of GRK5 in various immunopathological features associated with E.coli induced pulmonary infection using wild type (WT) and GRK5 knockout (KO) mice. Interestingly, 12-hours post-infection, GRK5KO exhibited significantly reduced inflammation and bacterial load as well as decreased neutrophils in the lung. Ex vivo assays demonstrated, GRK5KO and WT neutrophils have similar capacity to kill bacteria suggesting an early increase in neutrophils in the KO mice might decrease bacterial load. Consistent with this prediction, 4 hours post-infection, GRK5KO mice had markedly elevated neutrophil numbers in the lungs, compared to the WT mice. Interestingly, at later time points after infection (12 hours) even though the neutrophil (Ly6G+) numbers were reduced in the KO, the number of efferocytosing macrophages (Ly6g+ F4/80+) were markedly higher in the GRK5KO animals, suggesting that GRK5 deficiency advances the inflammatory resolution phase (increased efferocytosing macrophages). Taken together, our results show that GRK5 deficiency improves pulmonary infection and inflammation likely via early-enhanced neutrophil recruitment as well as swifter clearance of neutrophils in the lung.
Insulin activates myelin basic protein (p42 MAP) kinase by a protein kinase C-independent pathway in rat adipocytes: Dissociation from glucose transport

Myelin basic protein kinase (MBPK) activity of rat adipocytes was measured directly or in gels after purification of p42 microtubule-associated protein kinase (MAPK). Insulin and phorbol esters provoked 2- to 3-fold increases in MBPK/MAPK activity within 5-10 min. Whereas phorbol ester effects were blocked by protein kinase C (PKC) depletion or inhibition, insulin effects were fully intact, indicating that insulin activates MBPK/MAPK independently of PKC. In contrast, PKC depletion or inhibition markedly inhibited insulin effects on [3H]2-deoxyglucose uptake, suggesting that this effect requires PKC, rather than a factor within the ras/MAPK cascade.
The Mechanical Significance of Clasping Leaf Sheaths in Grasses: Evidence from Two Cultivars of Avena sativa

L'objectif de cette etude est de determiner si les gaines tubulaires foliaires d'Avoine contribuent au comportement mecanique des tiges articulees et comment cette contribution evolue avec le developpement
Structural aspects of the reaction center of photosynthetic bacteria calculated from triplet state zero-field splittings

Since the original observation of photoexcited triplet-state EPR spectra in reaction centers of photosynthetic bacteria by Leigh and Dutton [l-4], there has been a considerable amount of magnetic resonance data accumulated on the triplet states of the pigment molecules, reaction centers and whole cell systems of photosynthetic bacteria [5-91. Zero-field splittings have been measured for the photoexcited triplet state of bacteriochlorophyll a and bacteriochlorophyll b and for a variety of bacterial systems containing these molecules [7,9]. The triplet state data for the bacterial systems have been interpreted as arising from a bacteriochlorophyll dimer within the reaction center observed when the primary electron acceptor has been reduced [4,6]. It has been shown in previous work [6,8,10], that the triplet state properties of a dimer in which the triplet excitation is shared between the two molecules may be calculated from the properties of the monomer and the geometry of the pair. Therefore, since the bacteriochlorophyll triplet state properties are known, the photoexcited triplet state can be used as a probe to investigate the orientation of the pigment molecules in the special pair [6] present in the reaction center of bacterial systems. Since the zero-field splittings are available for a large number of bacteria, we have utilized these data, along with the most recently published bacteriochlorophyll pigment zero-field splittings [8,9] to determine the relative orientation of the pair molecules in the reaction center for the presently
The long haul: risks associated with livestock transport.

301 THE FOOD AND AGRICULTURE ORGANIZATION (FAO) of the United Nations describes live animal transport as “ideally suited for spreading disease,” given that animals may originate from different herds or flocks and are “confined together for long periods in a poorly ventilated stressful environment.”1 Given the associated “serious animal and public health problems,” the Federation of Veterinarians of Europe has called for the replacement of the longdistance transportation of live animals for slaughter as much as possible to a “carcass-only trade.”2 In the United States, more than 50 million live cattle, sheep, and pigs3 and an unknown number of the more than 9 billion chickens, turkeys, and other birds raised for food4 are annually traded across state lines. Before they are slaughtered, U.S. livestock may travel an average of 1,000 miles.5 These factors and activities may have undesirable animal and public health implications.
Webcams, Interactive Index Maps, and Our Brave New World’s Brave New Globe

Intermittent video supplied by a webcam affords near-real-time images that can approximate the dynamic scenes of full-motion video. As map supplements, webcam images offer readily interpreted on-the-spot reports of traffic flow, crowdedness, cloudiness, scenic beauty (or ugliness), and other directly observable aspects of the physical and human landscapes. And as easily interpreted cartographic point symbols, webcam images offer a range of visual variables, including size, numerousness, texture, rate of change, and value. Readily integrated with the maps, photographs, other images and the narrative text of electronic atlases and atlas-like websites, webcam images depend upon maps in two ways: locator maps provide the spatial context without which many webcam images have little meaning, and index maps help viewers identify places for which webcam images are available. As a medium for monitoring landscapes and watching people—with or without the subject’s awareness and acquiescence—the webcam is symptomatic of electronic cartography’s newfound capacity as a technology of surveillance.
Phylogeny of Hydrophiloidea (Coleoptera: Staphyliniformia) using characters from adult and preimaginal stages

A phylogenetic analysis using characters from egg cases, larvae, pupae and adults was conducted; the outgroups included the beetle families Silphidae, Hydraenidae and Histeridae. Characters from the immature stages were obtained mostly from material reared in the laboratory, those from the adults were obtained from Hansen's generic revision for the superfamily. The results support the position of Hydraenidae within the Staphylinoidea, and not as part of Hydrophiloidea; Histeroidea is proposed as the sister group of Hydrophiloidea. At family level two clades are distinguished; the relationships within the first clade are ((Georissidae Epimetopidae) Helophoridae), those within the second are ((Hydrophilidae Spercheidae) Hydrochidae). Larval characters were most informative at the base of the tree, especially those associated with the spiracular atrium; adult characters were most informative at the apex of the tree.
Use of transtibial aimer via the accessory anteromedial portal to identify the center of the ACL footprint

Purpose To assess the ability of a transtibial aimer with a 7-mm off-set in a standardized position to reach the center of the ACL footprint on the femur through the AM portal.
Structural Explanations to Altered Drug Resistance Pathways in HIV-1 Non-Clade B Proteases

The majority of human immunodeficiency virus-1 (HIV-1) infections across the world result from non-B clades. CRF01_AE is predominantly seen in Southeast Asia and the protease differs by ∼10% when compared to the clade B protease. Polymorphisms in CRF01_AE are often associated with drug resistance in the clade B protease. CRF01_AE protease has been observed to develop the unique N88S mutation in response to nelfinavir (NFV) therapy which is not commonly seen in clade B protease. We present here, structural and binding thermodynamic data on CRF01_AE protease in order to explain how sequence polymorphisms within CRF01_AE protease might affect its activity as well as to explain the altered NFV resistance pathway observed in CRF01_AE. The crystal structure of HIV-1 CRF01_AE N88S protease in complex with Darunavir (DRV) was determined to a resolution of 1.76 A and was compared with the clade B protease in complex with DRV. The CRF01_AE structure shows a significant change in the flap hinge region of the protease when compared to the clade B structure. The Ser88 side chain in the CRF01_AE structure is involved with a novel network of hydrogen bonds and interacts with the side chain of Asp30. This likely disrupts a critical hydrogen bond required for NFV binding. Binding constants and thermodynamic parameters for CRF01_AE and clade B protease were determined by isothermal titration calorimetry (ITC). Calorimetric data indicate that wild type CRF01_AE protease has ten fold and two fold weaker to NFV and DRV respectively when compared to clade B protease. This weakened affinity may permit the alternative pathway for NFV resistance via N88S, which is a mutation outside the active site.
Diversity in Graduate Nursing Education: An Experience in Collaboration

The recent shift in public policy away from the use of affirmative action programs in the admissions process of institutes of higher learning has motivated colleges and universities to explore alternative means for achieving their goal to increase the diversity of their student bodies. The imperative to promote diversity is particularly relevant in nursing education because there is an emphasis on preparing students to enter a profession that is committed to providing health care to all regardless of gender, race, ethnicity, or socioeconomic background. In 1997, the nursing programs at 2 Florida schools-Bethune-Cookman College (B-CC), a historic African-American college, and the University of Florida (UF), a land-grant university-initiated a collaborative relationship with the goals of improving access to graduate education for B-CC graduates and increasing the diversity of the graduate student body at UF. A central component of the collaboration is the Gator-Cats Mentoring Program in which students are recruited through career counseling and financial planning, mentored through the application process and the program, and offered continuing support in the skills required in graduate studies. This collaboration can serve as a model for other institutions seeking effective ways of increasing the diversity of their student populations.
Effect of autacoid modulation on N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity.

N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide which has been shown to induce acute tubular necrosis. The purpose of the present study was to determine if creatinine clearance was altered early in the development of NDPS nephrotoxicity. This study also examined the effect of autacoid modulation on the renal effects induced by NDPS and two metabolites of NDPS, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA). In one set of experiments, male Fischer 344 rats (4 rats/group) were administered a single intraperitoneal (i.p.) injection of NDPS (1.0 mmol/kg) or vehicle and creatinine clearance was determined at 3 and 6 h post-treatment. NDPS administration resulted in a marked decrease in creatinine clearance at both time points. In a second set of experiments, rats (4-8 rats/group) were pretreated with the cyclooxygenase inhibitor indomethacin (3.0 or 5.0 mg/kg, i.p.) or the thromboxane synthase inhibitor dazmegrel (20 mg/kg, i.p.) 1 h before the i.p. administration of NDPS (0.2 or 0.4 mmol/kg), NDHS (0.05 or 0.1 mmol/kg), NDHSA (0.05 or 0.1 mmol/kg) or vehicle. Indomethacin pretreatment potentiated the nephrotoxic potential of NDPS and its two metabolites, while dazmegrel pretreatment attenuated NDPS nephrotoxicity without marked effects on NDHS or NDHSA nephropathy. These results indicate that renal hemodynamic changes occur early in the development of NDPS nephrotoxicity and that autacoids are important modulators of NDPS- and NDPS metabolite-induced renal effects.
Muon Capture in Oxygen-16

The muon capture rate in oxygen is used as a means for measuring the induced pseudoscalar coupling constant (${C}_{P}$) of weak interactions. The capture rate between the ${J}^{P}={0}^{+}$ ground state of ${\mathrm{O}}^{16}$ and the ${0}^{\ensuremath{-}}$, ${1}^{\ensuremath{-}}$, ${2}^{\ensuremath{-}}$, and ${3}^{\ensuremath{-}}$ states of ${\mathrm{N}}^{16}$ are calculated as a function of ${C}_{P}$ with different nuclear models. Using the experimental values of the transition rates, we then determine ${C}_{P}$. We find that the transition rate, and therefore ${C}_{P}$, depends strongly on the nuclear model. We conclude that $5l\frac{{C}_{P}}{{C}_{A}}l20$.
In defense of the grammatical approach to local implicatures

The existence of “local implicatures” has been the topic of much recent debate. The purpose of this paper is to contribute to this debate by asking what we can learn from three puzzles, namely, the cancellation of such implicatures by or both, their behavior in the complement clauses of negative factive verbs such as sorry, and their behavior in root and embedded questions. Two basic approaches to local implicatures have been advanced: a fully pragmatic account in which local implicatures result from conventional Gricean principles and a semantic account according to which the generation of implicatures is interwoven with compositional, grammatical mechanisms. We argue that the lesson to be learned from our three case studies is that some kind of approach along the latter, grammatical line is necessary to account for the data.
Health care for all

If the United States is to come close to universal coverage, personal responsibility will need to play a larger role than it did in the mid-20th-century welfare state. Dr. M. Gregg Bloche asks if there is room for a new compact between citizen and state along these lines.
Towards a pedagogy of the incomprehensible: trauma and the imperative of critical witness in literacy classrooms

In this article, I explore questions about what it means to carry, live and invite traumatic stories into the space of a literacy classroom. Weaving illustrative moments from the classroom with trauma theory and research, I ask, What does it mean to embrace the incomprehensible in literacy classrooms? How might the incomprehensible be viewed as a productive and connected space in students’ academic and social experiences in schools? To delve into these questions, I turn to scholars who conceptualize trauma and its relationship with what we can access through and at the limits of articulation and to two young children’s writing and talk. In particular, I situate children’s experiences in trauma studies scholar Caruth’s ideas about the inadequacy of language in the face of trauma and cultural theorist Massumi’s arguments about affect as that which escapes our efforts to structure experience. I argue that incomprehensibility invokes an important metaphorical space of not knowing that demands reciprocal appro...
The relationship of purine metabolism to the macrophage-mediated increase of high energy phosphates in skeletal muscle☆

Abstract Previous investigations have demonstrated that the high energy phosphate and adenine nucleotide content of wounded tissue are decreased. Purine metabolism was investigated in incubated λ-carrageenan wounded skeletal muscle and in muscle exposed to peritoneal macrophages or macrophage-conditioned media. Wounded muscle released predominately uric acid into the incubation medium; whereas, nonwounded muscle released inosine, hypoxanthine, and xanthine as well as uric acid. Macrophages incubated with nonwounded muscle changed the purine release pattern toward one of wounded muscle. The conversion of inosine to allantoin and uric acid by macrophages increased linearly with the addition of up to 1 × 10 7 macrophages per incubation. Muscles incubated in macrophage-conditioned media had a decreased release of inosine and hypoxanthine and higher tissue levels of creatine phosphate, ATP, ADP, AMP, and adenosine compared to muscles incubated in standard media. These data suggest that the macrophage determines the pattern of purine release from wounded skeletal muscle in the incubated system and that in conditioned media a high energy phosphate promoting factor may exert its effect by mechanisms that augment the adenine purine pool.
Field programmable gate arrays in space

The use of field programmable gate arrays (FPGAs) in satellite and other spacecraft is on the rise. They are increasingly competitive when compared to traditional application-specific integrated circuits (ASICs). However, exposure to space radiation produces the same physical effects on both FPGAs and ASICs. How these radiation effects can translate to circuit malfunctions and how these problems can be prevented or mitigated is a complex, multifaceted issue that depends on the specific technology and the device's internal architecture. First and foremost, designers should implement a reliable ASIC/FPGA development methodology for the definition, design, verification, physical implementation and validation phases of any ASIC/FPGA to be flown as part of the spacecraft platform or critical payload. This should be contractually enforced. The European Space Agency (ESA) will continue to make available its own internal standard or any other equivalent methodology proposed by the contractor. As soon as the new ECSS standard on this subject is available, ESA will start using it as an applicable document in all projects where ASICs or FPGAs are to be developed.
Mortality of workers hired during World War II

There has been some suggestion that men first hired during World War II do not show the typical healthy worker effect and may have been more unhealthy than their counterparts who entered military service. We have studied 41,000 workers at six plants to determine whether men hired during World War II had higher mortality than men hired just before or after WWII. No evidence was found of any “unhealthy WWII worker” effect. © 1993 Wiley-Liss, Inc.
Supply-side asymmetry and the non-neutrality of demand fluctuations

Using annual data for a sample of developing and developed countries, the empirical evidence is consistent with a steeper supply curve in the face of positive demand shocks compared to negative shocks for many countries. For these countries, demand fluctuations are consistent with a net positive contribution to trend price inflation and a net negative contribution to trend output growth. These results challenge the long-term neutrality of demand fluctuations.
Toward a general mechanism of electron capture dissociation

The effects of positive charge on the properties of ammonium and amide radicals were investigated by ab initio and density functional theory calculations with the goal of elucidating the energetics of electron capture dissociation (ECD) of multiply charged peptide ions. The electronic properties of the amide group in N-methylacetamide (NMA) are greatly affected by the presence of a remote charge in the form of a point charge, methylammonium, or guanidinium cations. The common effect of the remote charge is an increase of the electron affinity of the amide group, resulting in exothermic electron capture. The N—C α bond dissociation and transition state energies in charge-stabilized NMA anions are 20–50 kJ mol−1 greater than in the hydrogen atom adduct. The zwitterions formed by electron capture have proton affinities that were calculated as 1030–1350 kJ mol−1, and are sufficiently basic for the amide carbonyl to exothermically abstract a proton from the ammonium, guanidinium and imidazolium groups in protonated lysine, arginine, and histidine residues, respectively. A new mechanism is proposed for ECD of multiply charged peptide and protein cations in which the electron enters a charge-stabilized electronic state delocalized over the amide group, which is a superbase that abstracts a proton from a sterically proximate amino acid residue to form a labile aminoketyl radical that dissociates by N—C α bond cleavage. This mechanism explains the low selectivity of N—C α bond dissociations induced by electron capture, and is applicable to dissociations of peptide ions in which the charge carriers are metal ions or quaternary ammonium groups. The new amide superbase and the previously proposed mechanisms of ECD can be uniformly viewed as being triggered by intramolecular proton transfer in charge-reduced amide cation-radicals. In contrast, remote charge affects N—H bond dissociation in weakly bound ground electronic states of hypervalent ammonium radicals, as represented by methylammonium, CH3NH 3 · , but has a negligible effect on the N—H bond dissociation in the strongly bound excited electronic states. This refutes previous speculations that loss of “hot hydrogen” can occur from an excited state of an ammonium radical.
Combining Writing and the Electronic Media in Sales Management Courses

As universities advance into high-tech learning, we need to study how moving traditional business writing styles into the electronic media may reflect or change the communication styles of managers and sales representatives. To accomplish this task, the authors developed writing assignments that focused on communicating via electronic messaging (e-mail).
Stopcock lumen contamination does not reflect the full burden of bacterial intravenous tubing contamination: Analysis using a novel injection port

Background: Prior clinical studies have used injection port lumen culture as a marker of intravenous (IV) fluid system contamination. We hypothesized that culturing injected saline (effluent) is a more sensitive method of detecting IV fluid system bacterial contamination than lumen culture. To test this hypothesis, we compared the incidence of lumen contamination with effluent contamination in a simulated setting. We also measured the effect of a novel injection port protective device (Port Guide; Matrix Tooling, Inc, Wood Dale, IL) on contamination. Methods: In this ex vivo study, 33 providers performed 5 injections of 1 mL sterile saline into each of 4 injection port designs: (1) stopcock, (2) stopcock with Port Guide, (3) stopcock with disinfectable needleless closed connector (DNCC), and (4) stopcock with DNCC and Port Guide. The primary outcome was the rate of effluent contamination with simultaneously contaminated injection port lumen. Results: Bacterial organisms were recovered from the effluent in 17 of the 132 injection ports evaluated. Of those 17 injection ports with contaminated effluent, 4 injection port lumens were simultaneously contaminated (24%). Additionally, use of the stopcock with Port Guide significantly reduced effluent contamination. Conclusion: Effluent culture is a more sensitive marker of IV fluid system contamination than injection port lumen culture. A novel protective device on the stopcock (Port Guide) significantly reduced IV fluid system bacterial contamination.
Relative saprophytic competence of Rhizobium japonicum strains in soils as determined by the quantitative fluorescent antibody technique (FA)

Abstract Experiments were conducted to estimate the saprophytic competence of four Rhizobium japonicum strains (110, 123, 532c, and 586) in a Rossmoyne silt loam (almost free of R. japonicum ) and a Miamian silt loam (containing indigenous R. japonicum strains). All strains increased about 100-fold in sterilized Rossmoyne or Miamian soil during the first 2 weeks, and the population remained constant for 26 and 6 weeks respectively. Such results indicated that abiotic factors were not limiting Rhizobium populations in these soils under laboratory conditions. There was no inter-strain competition when strains were mixed and applied to either sterilized soil. All R. japonicum strains decreased about ten-fold but survived well in non-sterile Rossmoyne soil during 26 weeks incubation. But, all strains died at varying rates in non-sterile Miamian soil during a 6 week incubation. The most rapid decline occurred with strain 123, which decreased about 1000-fold during the first 5 days, while strain 586, decreased about 1000-fold during the first 10 days. The die-back of strain 123 was found to coincide with an increase in numbers of a parasitic microorganism which passed through a 0.45 μm pore-sized filter. A bacteriophage has been implicated, although Bdellovibrio cannot be ruled out completely. This parasitic microorganism is strain specific but does not lyse a field isolate of serogroup 123.
Adhesion through L-selectin requires a threshold hydrodynamic shear

Selectins are cell adhesion molecules that bind carbohydrate ligands and promote interaction between leukocytes and the vessel wall in vascular shear flow. Selectin-ligand bonds have high mechanical strength, allowing initial tethering to the vessel wall through one or few bonds, and have fast on and off rates, permitting rolling in response to hydrodynamic drag. The L-selectin molecule on leukocytes binds to peripheral node addressin on high endothelial venules of lymph nodes to mediate leukocyte rolling and binds to a ligand on neutrophils to mediate rolling of leukocytes over one another. Here we describe a surprising mechanism for regulation of these interactions, both in vitro and in vivo. Shear above a critical threshold is required to promote and maintain rolling interactions through L-selectin, but not through E-selectin, P-selectin or VCAM-1. The shear threshold requirement for L-selectin may be physiologically important in low shear to prevent inappropriate aggregation of leukocytes and interaction with the vessel wall.
A Bayesian method for the synthesis of evidence from qualitative and quantitative reports: the example of antiretroviral medication adherence.

Objectives:Bayesian meta-analysis is a frequently cited but very little-used method for synthesizing qualitative and quantitative research findings. The only example published to date used qualitat...
The DOUTH2 Relation as a Dramatic Signifier in Wagner's Music Dramas

Near the conclusion of his article on 'Cohn Functions',l which is based on previous work by Richard Cohn2 and Jack Douthett, David Lewin briefly discusses the DOUTH2 relation, where two discarded pitch classes in a tetrachord are replaced with notes a semitone removed. In particular, he applies this parsimonious voice-leading paradigm to certain pairings of the half-diminished seventh chord and its inversionally related major-minor seventh [0, 2, 5, 8]. Since the interval vector of each individual sonority (0121 1 1 ) features a pair of minor thirds and one tritone, transpositions by T3, 6 or 9 likewise display a DOUTH2 voice-leading through the retention of two common notes and chromatic motion.3 As Lewin demonstrates, paired couplings of the two different chords result in no less than six instances of this same paradigm. The initial six graphs of Fig. la plot these transposition/ inversion possibilities onto a pitch matrix. The enclosed half-diminished Tristan chord (F-B-D:-G:) serves as the initial referential set for the T/I index numbers;4 dotted lines denote its inversional counterpart (the majorminor seventh).5 Since all six T/I relations cannot be demonstrated on a traditional Riemann Tonnetz, a left-to-right whole-tone diagonal replaces the usual semitone diagonal. In this way; the interval cycles in each row, column or diagonal incorporate only those interval-classes which appear in the sonorities' vector. The intervallic relation between the two invariant notes in the initial six progressions accounts for each interval-class in the vector. This property likewise holds true for the remaining interval in the first chord, as well as between the pair of new pitches which appear in the second major-minor seventh chord. These six T/I index numbers form an incomplete octatonic set: [0, 1, 3, 4, 9, 10]. In the remaining pair which completes this eight-note collection, T6/I holds three notes invariant while all of the voices in T7/I proceed by semitone.6 Fig. 1 b illustrates a continuous progression which successively utilises all six DOUTH2 relations in pairings of the two
Leukocytospermia in male infertility patients in China

Summary. Recent studies have revealed a high prevalence of leukocytospermia (> 1 × 106 white blood cells ml−1 semen) in male infertility patients in the USA and certain European countries, and have implicated white blood cells as a cause of infertility. Since leukocytospermia may often be attributed to male genital-tract infections, its prevalence could vary widely in different populations depending on factors such as sexual practices and the prevalence of sexually transmitted pathogens. In the study described here the incidence of leukocytospermia was determined in a group of 101 male infertility patients and a small reference group of normal fertile men in Beijing, China. Seminal white blood cells (WBC) and WBC sub-populations were enumerated by peroxidase staining and immunohistological assay. Eight out of 101 (7.9%) samples from infertility patients and 0/10 samples from fertile donors were leukocytospermic. The incidence of leukocytospermia in the Chinese infertility patients was considerably lower than the 23% incidence observed in a recent study of infertility patients in the USA using a similar technique. All but one of the patients with leukocytospermia had a poor sperm count and/or poor sperm motility. However, due to the low incidence of leukocytospermia and the small number of patients in this group, a statistically significant association between leukocytospermia and poor semen quality was not attained. The simple peroxidase test correlated well with the more expensive and technically demanding immunohistological assay for detection of white blood cells in semen.