cssi/SciSciGPT-SciSciNet huggingface dataset:
Human Motor Neurons With SOD1-G93A Mutation Generated From CRISPR/Cas9 Gene-Edited iPSCs Develop Pathological Features of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by gradual degeneration and elimination of motor neurons (MNs) in the motor cortex, brainstem, and spinal cord. Some familial forms of ALS are caused by genetic mutations in superoxide dismutase 1 (SOD1) but the mechanisms driving MN disease are unclear. Identifying the naturally occurring pathology and understanding how this mutant SOD1 can affect MNs in translationally meaningful ways in a valid and reliable human cell model remains to be established. Here, using CRISPR/Cas9 genome editing system and human induced pluripotent stem cells (iPSCs), we generated highly pure, iPSC-derived MNs with a SOD1-G93A missense mutation. With the wild-type cell line serving as an isogenic control and MNs from a patient-derived iPSC line with an SOD1-A4V mutation as a comparator, we identified pathological phenotypes relevant to ALS. The mutant MNs accumulated misfolded and aggregated forms of SOD1 in cell bodies and processes, including axons. They also developed distinctive axonal pathologies. Mutants had axonal swellings with shorter axon length and less numbers of branch points. Moreover, structural and molecular abnormalities in presynaptic and postsynaptic size and density were found in the mutants. Finally, functional studies with microelectrode array demonstrated that the individual mutant MNs exhibited decreased number of spikes and diminished network bursting, but increased burst duration. Taken together, we identified spontaneous disease phenotypes relevant to ALS in mutant SOD1 MNs from genome-edited and patient-derived iPSCs. Our findings demonstrate that SOD1 mutations in human MNs cause cell-autonomous proteinopathy, axonopathy, synaptic pathology, and aberrant neurotransmission.
Semi-global Quad Mesh Structure Simplification via Separatrix Operations

This paper presents a semi-global method to simplify the structure of an all-quad mesh. The simplification aims to reduce the number of singularities, while preserving boundary features. The simplification operations of our method are based on the separatrices connecting adjacent singularities. The proposed semi-global method can handle quad-meshes with complex structures (e.g., quad-meshes obtained via Catmull-Clark subdivision of the triangle meshes) and produce quad meshes with much simpler structures.
Using Machine Learning Techniques to Estimate the Remaining Useful Life of a System with Different Types of Datasets

Intelligent Prognostics and Health Management (PHM) technology aims to estimate the Remaining Useful Life (RUL) of a subsystem or a component using data collected by sensors. The rise in the complexity of systems requires new models to capture the relationship between the sensors and the RUL. Novel deep Convolutional Neural Networks (CNN) have been proposed as an approach for estimating the RUL. However, large amount of data is needed to use Machine Learning (ML) techniques. We explore current ML methods being used with different types of datasets and provide a conclusion on deciding what learning method works best with unique datasets. We find that, for most systems, the ML method used highly depends on the dataset and can greatly decrease the cost and increase the reliability.
Enhanced Test and Verification Capabilities Using Model-Based Design

The use of executable models to simulate and design embedded software for automotive systems is well-established in automotive engineering. Leveraging those same models to automatically generate those software components is becoming part of mainstream development processes, using Model-Based Design approaches. Today, the value of these models for testing, verifying, and validating software applications is typically through hardware-in the-loop simulation. However, new and enhanced test and verification approaches are emerging that leverage these models to address today’s complex embedded systems, including both software and electronic components. This paper describes these approaches and their use in Model- Based Design.
Multidisciplinary treatment of opioid use disorder in primary care using the collaborative care model.

Background: Treatment of opioid use disorder (OUD) is highly effective, but access is limited and care is often fragmented. Treatment in primary care can improve access to treatment and address psy...
Behavioral Bandits: Analyzing the Exploration Versus Exploitation Trade-Off in the Lab

This paper uses a laboratory experiment to analyze how individuals resolve an exploration versus exploitation trade-off. The experiment implements a single-agent exponential bandit model. We find that, as predicted, subjects respond to changes in the prior belief, safe action, and discount factor. However, we commonly find that subjects give up on exploration earlier than predicted. We estimate a structural model that allows for risk aversion, base rate neglect/conservatism, and probability mis-weighting. We find support for risk aversion, conservatism, and probability mis-weighting as potential factors that influence subject behavior. Risk aversion appears to explain the finding that subjects explore less than predicted.
Veterans on anticancer medications in rural and community environment support (VA CARES) program: A pharmacist-led telemedicine medication management program for veterans receiving oral antineoplastic therapies through the MISSION Act.

1545Background: Cancer therapies are leveraging oral targeted treatments over traditional cytotoxic chemotherapy (CT) at an increasing rate. Compared to CT, use of oral antineoplastic treatments (O...
Tocilizumab Is Safe after T-Cell Replete Peripheral Blood Haploidentical Donor Transplantation

Abstract Introduction: Allogeneic hematopoietic cell transplantation is a cornerstone of therapy for hematologic malignancies and often a patient's only curative intent treatment. Overall outcomes for haploidentical transplantation appear to be excellent, however, this novel approach brings toxicities that are particular to its biological and clinical milieu. We previously described occurrence of severe cytokine release syndrome (CRS) after haplo-HCT. Severe CRS was associated with poor clinical outcomes, including transplant related mortality (TRM), overall survival (OS), and neutrophil engraftment (Abboud et al, BBMT, 10/2016). Furthermore, tocilizumab rapidly reversed the signs and symptoms of the dysregulated inflammatory reaction in most cases of CRS. Here we compare short and long term complications in peripheral blood haplo-HCT patients who did and did not receive tocilizumab. Patients and Methods: We performed a retrospective review of patients who underwent haplo-HCT transplantation at our institution from July 2009 through January 2017. A total of 169 patients were identified, 9% (15) received tocilizumab for treatment of CRS. We compared rates of acute and chronic GVHD, time to relapse, and incidence infection related deaths between patients who received tocilizumab and those who did not. Results: We found no difference in acute GVHD (hazard 1.08, p 0.83), time to relapse (hazard 1.06, p 0.90), or incidence of infection related deaths (hazard 0.764, p 0.65) between patients who received tocilizumab and those who did not. There was a trend towards a lower rate of chronic GVHD in patients who received tocilizumab compared with those who did not, with a hazard of 0.56 (95% CI 0.158 - 0.99, p= 0.37). Conclusions: Tocilizumab is safe following haplo-SCT. Tocilizumab did not increase the risk of acute GVHD, chronic GVHD, time to relapse, or incidence of infection related deaths. There was a trend towards a lower rate of chronic GVHD in patients who received tocilizumab. Download : Download high-res image (101KB) Download : Download full-size image Figure . Disclosures Uy: Boehringer Ingelheim: Consultancy; Novartis: Consultancy, Other: Travel Suppport; GlycoMimetics: Consultancy. Vij: Celgene: Honoraria; Konypharma: Honoraria; Bristol-Meyers-Squibb: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Jazz: Honoraria; Abbvie: Honoraria; Janssen: Honoraria.
Nurses in HIV Care in Eastern Europe: Past, Present, and Future

The chapter focuses on the role of nurses in Eastern European healthcare system with specific focus on HIV care. It refers to the beginnings of Soviet health care, describes the system and formation of cadres of nurses, addresses changes that happened in mid 1990s in the region and the need to strengthen the role of nurses in medical community related to ageing population, increase of chronic diseases and appearance of new diseases like HIV. The chapter describes the functions of nurses in the healthcare system, discusses the need to increase the role of the nurses, boosts the prestige of the profession, and points to the areas of education and training that would be needed for the future. The chapter refers to the ongoing work of the World Health Organisation (WHO) to strengthen the role of nurses through task shifting and task sharing to implement people-centred care for people who live with HIV.
A day in the life: a qualitative study of clinical decision-making and uptake of neurorehabilitation technology.

Author(s): Celian, Courtney; Swanson, Veronica; Shah, Maahi; Newman, Caitlin; Fowler-King, Bridget; Gallik, Sarah; Reilly, Kaitlin; Reinkensmeyer, David J; Patton, James; Rafferty, Miriam R | Abstract: BackgroundNeurorehabilitation engineering faces numerous challenges to translating new technologies, but it is unclear which of these challenges are most limiting. Our aim is to improve understanding of rehabilitation therapists' real-time decision-making processes on the use of rehabilitation technology (RT) in clinical treatment.MethodsWe used a phenomenological qualitative approach, in which three OTs and two PTs employed at a major, technology-encouraging rehabilitation hospital wrote vignettes from a written prompt describing their RT use decisions during treatment sessions with nine patients (4 with stroke, 2 traumatic brain injury, 1 spinal cord injury, 1 with multiple sclerosis). We then coded the vignettes using deductive qualitative analysis from 17 constructs derived from the RT literature and the Consolidated Framework for Implementation Research (CFIR). Data were synthesized using summative content analysis.ResultsOf the constructs recorded, the five most prominent are from CFIR determinants of: (i) relative advantage, (ii) personal attributes of the patients, (iii) clinician knowledge and beliefs of the device/intervention, (iv) complexity of the devices including time and setup, and (v) organizational readiness to implement. Therapists characterized candidate RT as having a relative disadvantage compared to conventional treatment due to lack of relevance to functional training. RT design also often failed to consider the multi-faceted personal attributes of the patients, including diagnoses, goals, and physical and cognitive limitations. Clinicians' comfort with RT was increased by their previous training but was decreased by the perceived complexity of RT. Finally, therapists have limited time to gather, setup, and use RT.ConclusionsDespite decades of design work aimed at creating clinically useful RT, many lack compatibility with clinical translation needs in inpatient neurologic rehabilitation. New RT continue to impede the immediacy, versatility, and functionality of hands-on therapy mediated treatment with simple everyday objects.
Tobramycin suppresses cystic fibrosis lung inflammation by increasing 5' tRNA-fMet halves secreted by P. aeruginosa

Abstract Although inhaled tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of P. aeruginosa in the lungs is only modestly reduced; hence, the mechanism whereby tobramycin improves lung function remains unclear. Previously, we demonstrated that P. aeruginosa secretes outer membrane vesicles (OMVs) that fuse with bronchial epithelial cells (HBECs), delivering small RNAs (sRNAs) that suppress the host immune response. Thus, we hypothesized that tobramycin modifies the sRNA content of OMVs leading to reduced inflammation and neutrophil-mediated lung damage. We found that tobramycin increased the amount of two 5′ tRNA-fMet halves in OMVs (Tobi-OMVs) and that Tobi-OMVs elicited less IL-8 secretion by CF-HBECs than control OMVs (ctrl-OMVs). A specific 5′ tRNA-fMet halves inhibitor reduced the ability of Tobi-OMVs to suppress IL-8 secretion. Tobi-OMVs were also less effective in stimulating KC secretion and neutrophil recruitment in mouse lungs compared to ctrl-OMVs. Tobramycin also reduced IL-8 and neutrophil abundance in bronchoalveolar lavage fluid obtained from pwCF. The 5′ tRNA-fMet halves reduced IL-8 secretion by an AGO2-mediated post-transcriptional regulatory mechanism. The clinical benefit of tobramycin is partly due to an increase in the secretion of 5′ tRNA-fMet halves in OMVs, leading to the attenuation of IL-8 and neutrophil-mediated CF lung damage.
Indications and Types of Bladder Augmentation in Cloacal Exstrophy

Cloacal exstrophy is the most severe form of the bladder exstrophy complex. It represents the greatest challenge because not only is the bladder, bladder neck, urethra, and genitalia involved with this deformity and malformation, but the intestine may be severely shortened and innervation to the bladder and bladder neck area may be abnormal because of spinal malformation (present in greater than 75% of these patients). Therefore, reconstruction for urinary continence is a major challenge.
Learning and Evolution: An Introduction to Non-darwinian Evolutionary Computation

The field of evolutionary computation has drawn inspiration from Darwinian evolution in which species adapt to the environment through random variations and selection of the fittest. This type of evolutionary computation has found wide applications, but suffers from low efficiency. A recently proposed non-Darwinian form, called Learnable Evolution Model or LEM, applies a learning process to guide evolutionary processes. Instead of random mutations and recombinations, LEM performs hypothesis formation and instantiation. Experiments have shown that LEM may speed-up an evolution process by two or more orders of magnitude over Darwinian-type algorithms in terms of the number of births (or fitness evaluations). The price is a higher complexity of hypothesis formation and instantiation over mutation and recombination operators. LEM appears to be particularly advantageous in problem domains in which fitness evaluation is costly or time-consuming, such as evolutionary design, complex optimization problems, fluid dynamics, evolvable hardware, drug design, and others.
Biogeochemical Conditions Favoring Magnetite Formation during Anaerobic Iron Reduction

Several anaerobic bacteria isolated from the sediments of Contrary Creek, an iron-rich environment, produced magnetite when cultured in combinations but not when cultured alone in synthetic iron oxyhydroxide medium. When glucose was added as a carbon source, the pH of the medium decreased (to 5.5) and no magnetite was formed. When the same growth medium without glucose was used, the pH increased (to 8.5) and magnetite was formed. In both cases, Fe2+ was released into the growth medium. Geochemical equilibrium equations with Eh and pH as master variables were solved for the concentrations of iron and inorganic carbon that were observed in the system. Magnetite was predicted to be the dominant iron oxide formed at high pHs, while free Fe2+ or siderite were the dominant forms of iron expected at low pHs. Thus, magnetite formation occurs because of microbial alteration of the local Eh and pH conditions, along with concurrent reduction of ferric iron (direct biological reduction or abiological oxidation-reduction reactions).
Sequence, expression, and polymorphism of the Peromyscus leucopus Mhc class Ib gene, M4.

The H2 M region harbors about 20 class I genes or gene fragments the function of which are largely obscure. The rat Mhc (RT1) appears to contain several orthologs of H2 M region genes although orthologs in more distantly related species have yet to be clearly identified. In this report, the sequence of a genomic clone containing a Peromyscus leucopus Mhc (Pele) class I gene is presented and based on sequence similarity was found to be the Pele ortholog of H2-M4. Unlike H2-M4, which is a pseudogene, PeleM4 appeared to be an intact Mhc class Ib gene. Appropriately splice PeleM4 mRNA transcripts were detected in the liver, lung, and thymus. Polymorphism of PeleM4 was examined by sequencing exon 2 and 3 of the PeleM4 gene from seven different Pele haplotypes and six PeleM4 alleles were identified. These results suggest that the existence of some H2 M region class Ib genes predates the divergence of Peromyscus and Mus genera which occurred 40–60 million years ago and provide an example of unique pathways in the evolution of Mhc class Ib genes.
Second Moment Relationships for Waiting Times in Queueing Systems with Poisson Input

For theM/G/1 queue there are well-known and simple relationships among the second moments of waiting time under the first-in-first-out, last-in-first-out, and random-order-of-service disciplines. This paper points out that these relationships hold in considerably more general settings. In particular, it is shown that these relationships hold forM/G/1 queues with exceptional first service,M/G/1 queues with server vacations, andM/G/1 queues with static priorities.
Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOI) are antidepressant drugs with efficacy similar to other classes of antidepressant drugs. Originally developed for treatment of tuberculosis, MAOI were the first clinically effective modern antidepressant drugs …
jContractor: A Reflective Java Library to Support Design by Contract

jContractor is a purely library based approach to support Design By Contract specifications such as preconditions, postconditions, class invariants, and recovery and exception handling in Java. jContractor uses an intuitive naming convention, and standard Java syntax to instrument Java classes and enforce Design By Contract constructs. The designer of a class specifies a contract by providing contract methods following jContractor naming conventions. jContractor uses Java Reflection to synthesize an instrumented version of a Java class by incorporating code that enforces the present jContractor contract specifications. Programmers enable the run-time enforcement of contracts by either engaging the jContractor class loader or by explicitly instantiating objects using the jContractor object factory. Programmers can use exactly the same syntax for invoking methods and passing object references regardless of whether contracts are present or not. Since jContractor is purely library-based, it requires no special tools such as modified compilers, modified JVMs, or pre-processors.
Family Characteristics, Public Program Participation, & Civic Engagement

This study tested for differences on the type and extent of civic engagement between use of visible programs such as Food Stamps and Medicaid and less visible programs such as the Earned Income Tax Credit while accounting for family and sociodemographic characteristics. Policy feedback theory guided the study which used data from the 1979 cohort of the National Longitudinal Surveys. Challenging prior research, means-tested Food Stamps, Medicaid, or EITC program participants were as likely as non-participants to devote time to activities aimed at changing social conditions. What social service agencies can do to enhance civic engagement is discussed.
Impaired mast cell-dependent natural immunity in complement C3-deficient mice

The complement system is widely regarded as essential for normal inflammation, not least because of its ability to activate mast cells. However, recent studies have called into question the importance of complement in several examples of mast cell-dependent inflammatory responses. To investigate the role of complement in mast cell-dependent natural immunity, we examined the responses of complement-deficient mice to caecal ligation and puncture, a model of acute septic peritonitis that is dependent on mast cells and tumour necrosis factor-alpha (TNF-alpha). We found that C4- or C3-deficient mice were much more sensitive to caecal ligation and puncture than wild-type (WT) controls (100% versus 20% in 24-h mortality, respectively). C3-deficient mice also exhibited reductions in peritoneal mast cell degranulation, production of TNF-alpha, neutrophil infiltration and clearance of bacteria. Treating the C3-deficient mice with purified C3 protein enhanced activation of peritoneal mast cells, TNF-alpha production, neutrophil recruitment, opsonophagocytosis of bacteria and resistance to caecal ligation and puncture, confirming that the defects were complement-dependent. These results provide formal evidence that complement activation is essential for the full expression of innate immunity in this mast cell-dependent model of bacterial infection.
Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

Abstract Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the Asd+ vector pYA292, and the construct was introduced into the avirulent delta cya delta crp delta asd S. typhimurium chi 3987 for oral immunization of birds. The gene encoding the 21-kDa protein was expressed equivalently in B. avium 197, delta asd E. coli chi 6097, and S. typhimurium chi 3987 and was localized primarily in the cytoplasmic membrane and outer membrane. In preliminary studies on oral inoculation of turkey poults with S. typhimurium chi 3987 expressing the gene encoding the B. avium 21-kDa protein, it was determined that a single dose of the recombinant Salmonella vaccine failed to elicit serum antibodies against the 21-kDa protein and challenge with wild-type B. avium 197 resulted in colonization of the trachea and thymus with B. avium 197.
Redundancy for yield enhancement in the 3-D computer

A prototype 3-D Computer which demonstrates the feasibility of the stacked wafer approach is discussed. The wafer-scale integrated circuits of the 3-D Computer have been carefully partitioned to enable redundancy to be used to insure high yields. Redundancy approaches, implementation issues, and testability both for the schemes used in the prototype and in future generations of the 3-D Computer are discussed. The circuits of the 32*32 array processor used 100% interstitial redundancy using one-way connectivity. The 128*128 array processor now underway construction, as well as a future larger array processor, use a mixture of redundancy schemes: a 50% redundancy with four-way connectivity for the array logic and 100% redundancy for the nearest-neighbor communication and control circuits. The 50% redundancy minimizes the area and test overhead for sparing while improving yields. >
Alanine catabolism in Klebsiella aerogenes: molecular characterization of the dadAB operon and its regulation by the nitrogen assimilation control protein.

Klebsiella aerogenes strains with reduced levels of d-amino acid dehydrogenase not only fail to use alanine as a growth substrate but also become sensitive to alanine in minimal media supplemented with glucose and ammonium. The inability of these mutant strains to catabolize the alanine provided in the medium interferes with both pathways of glutamate production. Alanine derepresses the nitrogen regulatory system (Ntr), which in turn represses glutamate dehydrogenase, one pathway of glutamate production. Alanine also inhibits the enzyme glutamine synthetase, the first enzyme in the other pathway of glutamate production. Therefore, in the presence of alanine, strains with mutations in dadA (the gene that codes for a subunit of the dehydrogenase) exhibit a glutamate auxotrophy when ammonium is the sole source of nitrogen. The alanine catabolic operon of Klebsiella aerogenes, dadAB, was cloned, and its DNA sequence was determined. The clone complemented the alanine defects of dadA strains. The operon has a high similarity to the dadAB operon of Salmonella typhimurium and the dadAX operon of Escherichia coli, each of which codes for the smaller subunit of d-amino acid dehydrogenase and the catabolic alanine racemase. Unlike the cases for E. coli and S. typhimurium, the dad operon of K. aerogenes is activated by the Ntr system, mediated in this case by the nitrogen assimilation control protein (NAC). A sequence matching the DNA consensus for NAC-binding sites is located centered at position −44 with respect to the start of transcription. The promoter of this operon also contains consensus binding sites for the catabolite activator protein and the leucine-responsive regulatory protein.
The early use of break-bone fever (Quebranta huesos, 1771) and Dengue (1801) in Spanish

The appellation of break-bone fever for dengue is attributed to the popular name given to the disease in the first described epidemic of an illness that is clinically compatible with dengue in Philadelphia in 1780. The origin of the word dengue as the name of an illness is currently attributed to the Swahili phrase Ka dinga pepo, thought to have crossed from Africa to the Caribbean in 1827; in Cuba this phrase was popularly identified with the Spanish word dengue. This article presents documents from Spanish archives that indicate the use of quebranta huesos (break-bone) by a physician in Puerto Rico to describe a febrile illness in 1771, and the use of the term dengue by the Queen of Spain in 1801 to describe an acute febrile illness with bone and joint pains, hemorrhage, and jaundice. These texts are evidence of a more generalized use of the term break-bone than previously recognized, and conversely, the specifically Spanish origin of dengue as the name for an illness.
Matrices and set differences

Let A and B be (0, 1)-matrices of sizes m by t and t by n, respectively. Let x"1, ..., x"t denote t independent indeterminates over the rational field Q and define X = diag[x"t, ..., x"t]. We study the matrix equation AXB = Y. We first discuss its combinatorial significance relative to topics such as set intersections and the Marica-Schonheim theorem on set differences. We then prove the following theorem concerning the matrix Y. Suppose that the matrix Y of size m by n has rank m. Then Y contains m distinct nonzero elements, one in each of the m rows of Y.
Chemically controlled pattern formation in phase-separating materials

The role of chemical reactions in the selection of patterns in phase-separating mixtures is presented. Linearized theory and computer simulation show that the initial long-wavelength instability characteristic of spinodal decomposition is suppressed by chemical reactions, which restrict domain growth to intermediate length scales even in the late stages of phase separation. Our findings suggest that chemical reactions may provide a novel way to stabilize and tune the steady-state morphology of phase-separating materials.
Hospice care in Japan

Hospice care was introduced in Japan in the 1970s. There are currently an estimated 21 programs, which are primarily hospital-based. This paper provides an overview of the history, current state, and future trends of hospice care in Japan. Four programs are described, including staffing information, length of stay, and prognoses of patients. Hospice care in Japan is compared to hospice care in the United States and major differences are described. Lastly, the concept of "truth telling" is explored within the context of the Japanese culture. The discussion is based on a review of the literature and a mailed survey completed by 16 Japanese hospice programs during July 1992. The paper is in four sections: An overview of Japan. The history, current state, and future trends of hospice care in Japan. The major differences between hospice care in Japan and the United States. An exploration of "truth telling" within the context of the Japanese culture.
HIV prevention evaluation: Current contributions and future directions

Abstract The articles in this special issue of AIDS Education and Prevention make significant contributions to the field of HIV prevention evaluation. Their salient and common themes fit well into the major types of evaluation—formative, process, outcome, impact, and economic—as do the important policy questions put forward at the beginning of this issue.
Allosteric effects on substrate dissociation from cytochrome P450 3A4 in nanodiscs observed by ensemble and single-molecule fluorescence spectroscopy.

Cytochrome P450 (CYP) 3A4 is a major human drug-metabolizing enzyme and displays pharmacologically relevant allosteric kinetics caused by multiple substrate and/or effector binding. Here, in the first single-molecule (SM) fluorescence studies of CYPs, we use total internal reflection fluorescence microscopy to measure residence times of the fluorescent dye Nile Red in CYP3A4 incorporated in surface-immobilized lipid Nanodiscs, with and without the effector α-naphthoflavone. We find direct evidence that CYP3A4 effectors can decrease substrate off-rates, providing a possible mechanism for effector-mediated enhancement of substrate metabolism. These interesting results highlight the potential of SM methods in studies of CYP allosteric mechanisms.
Transverse-current autocorrelation-function calculations of the shear viscosity for molecular liquids.

The usual approach to calculating shear viscosities and other thermal transport coefficients from equilibrium molecular-dynamics simulations has been to evaluate the appropriate Green-Kubo relation. An alternative to this method is to examine the long-time behavior of correlations formed from the amplitudes of spontaneous fluctuations in transverse momentum fields (transverse-current autocorrelation functions). For systems in the hydrodynamic limit, long-wavelength fluctuations in transverse momentum fields decay exponentially with a decay constant 1/${\mathrm{\ensuremath{\tau}}}_{\mathit{H}}$=\ensuremath{\mu}${\mathit{k}}^{2}$/\ensuremath{\rho}, where k is the wave vector of the fluctuation, \ensuremath{\mu} is the shear viscosity, and \ensuremath{\rho} is the density. Thus, determination of ${\mathrm{\ensuremath{\tau}}}_{\mathit{H}}$ leads directly to \ensuremath{\mu}. This approach is used to calculate the shear viscosity for the Lennard-Jones fluid, liquid carbon dioxide, and the TIP4P model of water of Jorgensen et al. [J. Chem. Phys. 79, 926 (1983)].
Beyond Broken Bonds and Broken Hearts: The Bonding of Theories of Attachment and Grief

Abstract Attachment theory describes the establishment and long-term impact of infants' early relationships. Theories of grief and mourning have acknowledged that the disruption of attachment bonds is loss and grief, but the attachment literature shows little development toward a conceptual linkage with these theories. The connection is important given the current discussion of whether bonds with the deceased are broken or continued. The purpose of this article is to link the strengths of each perspective to inform us about the process of grief as mourners work through the reconstruction of their relationships. It presents a developmental model integrating attachment theory and cognitive developmental approaches in order to further our understanding of the processes involved in loss and grief.
The sill depth of the mid-atlantic ridge in the equatorial region

Abstract Recent evidence confirms earlier theories that the deepest communication between the Eastern and Western Basins of the Atlantic Ocean lies in the region of the Romanche Trench where the Mid-Atlantic Ridge crosses the Equator. New topographic data presented elsewhere suggests that the path of deepest communication is along either the Romanche or the Chain Fracture Zone. Hydrographic station data support this and indicate that the controlling depth is about 3750 m, which is from 250–1000 m shallower than earlier estimates. Various factors including scatter of the temperature and salinity characteristics in the ocean, internal waves and seasonal or longer period surges associated with the formation of Antarctic Bottom Water in the Western Basin combine to make the effective oceanographic barrier deeper than the true topographic barrier. Scatter due to inaccuracies in the sampling and measuring techniques have the further effect of making the oceanographic barrier appear deeper than it otherwise would. Possible paths of flow of the deep water from Western to Eastern Basin are shown.
Effects of cyclophosphamide on visceral leishmaniasis in the mouse.

SYNOPSIS Cyclophosphamide (Cy), 125 or 200 mg/kg body weight, injected intraperitoneally (i.p.) into BALB/c mice one day before infection with amastigotes of Leishmania donovani, by the 8th day postinfection caused a significant decrease in the mean numbers of parasites in spleens and livers when compared to mice injected with phosphate buffered saline (PBS). When 125 mg/kg was injected into chronically infected mice (on day 34 of infection), however, within 2 days (day 36) mean parasite levels in both the spleens and livers were statistically greater than in PBS-treated controls. Similarly, when a series of 6 Cy injections, 50 mg/kg each, was injected over a period of 8 days during the chronic stage of infection, the mean parasite levels in both spleens and livers were significantly increased over those of PBS-treated controls. Druing the chronic stage of infection, Cy injections suppressed the immunity to superinfection. Neither plasma nor parasitized peritoneal macrophages obtained from Cy-treated mice, when compared to PBS-treated mice, differed in their respective capacities to influence the growth of intracellular amastigote of L. donovani in vitro. Passive transfer of hyperimmune mouse serum could not reverse the immunosuppressive effects of Cy upon chronic leishmaniasis in the mouse. It is suggested that neither readily demonstrable anti-leishmanial humoral factors nor “immune” macrophages per se, plays a major role in acquired immunity to leishmaniasis in the mouse.
Kinetic equations for the collisional plasma model

Using the collisional plasma model (CPM) representation, expressions are derived for the Vlasov operator both in its general form and in the drift-kinetic approximation following the recursive derivation by Hazeltine (1973). The expressions for the operators give easily calculated couplings between neighbouring components of the CPM representation. Expressions for various macroscopic observables in the drift-kinetic approximation are also given.
Heterogeneity of antibodies produced by single hemolytic foci.

Abstract Lethally irradiated male BDF 1 mice were injected with 10 7 bone marrow cells, 8 × 10 5 spleen cells, and sheep or goat red blood cells as antigens. The cross-reactivity between these red blood cells is approximately 40%, as determined by injecting normal mice with either sheep or goat red blood cells, removing their spleens 4 days later, and assaying all spleens for both antisheep and antigoat plaque-forming cells. Eight days after injection of bone marrow, spleen, and antigen, the spleens of the irradiated recipients were removed and assayed for the presence of hemolytic foci by the Playfair technique, and were found to contain an average of 0.7 foci/spleen. Earlier studies had demonstrated that such foci could contain plaque-forming cells derived from more than one precursor cell. The positive pieces comprising a single hemolytic focus were removed, pooled, and aliquots were assayed for direct and indirect plaque-forming cells to the immunizing antigen. Several foci were found to contain 17–82% as many plaque-forming cells lysing the cross-reacting antigen as lysed the immunizing antigen. These data indicate that these foci contained plaque-forming cells of two specificities: (1) plaque-forming cells which responded to determinants on the immunizing antigen only, and (2) plaque-forming cells which responded to determinants on both the immunizing and cross-reacting antigens. In addition, single foci were found which contained both direct and indirect plaque-forming cells lysing the immunizing antigen. Sixteen of 39 foci assayed contained more than twice as many indirect as direct plaque-forming cells. We concluded that a single hemolytic focus, probably derived from more than one precursor cell, could contain plaque-forming cells producing antibodies of more than one set of specificities and immunoglobulins of more than one type.
Information Processing Systems

Abstract The purpose of this paper is to describe and illustrate the process of obtaining selected information from large, computerized files, using a modern data base language, and to then pass this data subset to a mathematical model for further processing. The model may be imbedded in the same job step or it may be a separate job step. Similarly, there may be several subsets which must be extracted before the link to a model is made. The paper also demonstrates some of the fundamental advantages of a Data Base Language including macro-type statements, utility calls, hold files, simple sorts and the use of a Data Description Table (DDT) which may be incorporated in a program by a one line Call statement.
New York City's oyster gardeners: Memories and meanings as motivations for volunteer environmental stewardship

a b s t r a c t We conducted an exploratory study to determine the motivations of volunteer oyster gardeners in New York City (NYC), and the memories, meanings, and sense of place they associate with their work. Oyster gardeners are volunteers who place cages with young oysters at agreed upon locations, and monitor the oysters’ growth and survival. Open-ended interviews were conducted with 10 oyster gardeners and transcripts were coded to understand specific motivations, social–ecological memories and meanings, and sense of place, and how these relate to oyster gardening. Oyster gardeners’ social–ecological memories of and meanings related to oysters and the NYC estuary were tightly intertwined with their sense of place and motivations. These links suggest that whereas altruistic concern related to improving the environment is an important motivation for environmental volunteerism, the specific focus of environmental volunteerism may be driven by social–ecological memories, meanings, and sense of place derived from experiences with and the features of local places and species. In some cases, this process may rise to the level of creation or recognition of iconic species, which implies additional motivations for environmental volunteerism, including ecological and socio-cultural meanings attributed to species as well as fascination and related aspects of biophilia. The results suggest that government agencies and non-profits might consider a broader suite of functions that environmental stewardship serves for the volunteers, including attachment and memories related to particular species and places and their ecological, historical, and cultural values.
Effect of aflatoxin B-1 on the in vitro incorporation of 14C-acetate into human skin lipids.

Aflatoxin B1 hindert den in vitro Einbau des14C-Azetats in die Gesamtlipide, die freien Sterine, die Phospholipide und die Neutralfette der menschlichen Haut. Die Atmungsgeschwindigkeit der toxinbehandelten Gewebe wurde nicht beeinflusst.
Cracking the Combinatorial Semaphorin Code

In this issue of Neuron, Wu et al. describe a combinatorial code of repulsive Sema-2a and attractive Sema-2b signaling that mediates mechanosensory axonal guidance, fasciculation, and synaptic target selection within the CNS of Drosophila. Their work exemplifies how a detailed, multilevel molecular-genetic analysis (from molecules to behavior) provides fundamental insights into neural circuit development.
Magnetic hysteresis monitoring of Cretaceous submarine basaltic glass during Thellier paleointensity experiments: evidence for alteration and attendant low field bias

On the basis of studies of Holocene samples, submarine basaltic glass (SBG) is thought to be an ideal paleointensity recorder because it contains unaltered single domain magnetic inclusions that yield Thellier paleointensity data of exceptional quality. To be useful as a recorder of the long-term geomagnetic field, older SBG must retain these optimal properties. Here, we examine this issue through rock magnetic and transmission electron microscope (TEM) analyses of Cretaceous SBG recovered at Ocean Drilling Program Site 1203 (northwestern Pacific Ocean). These SBG samples have very low natural remanent magnetization intensities (NRM 2 /g) and TEM analyses indicate a correspondingly low concentration of crystalline inclusions. Thellier experiments on samples with the strongest NRM intensity (>5×10 −11 Am 2 ) show a rapid acquisition of thermoremanent magnetization (TRM) with respect to NRM demagnetization. Taken at face value, this behavior implies magnetization in a very weak (<17 μT) ambient field. But monitoring of magnetic hysteresis properties during the Thellier experiments (on subsamples of the SBG samples used for paleointensity determinations) indicates systematic variations in values over the same temperature range where the rapid TRM acquisition is observed. A similar change in properties during heating is observed on monitor SBG specimens using low-temperature data: with progressive heatings the Verwey transition becomes more distinct. We suggest that these experimental data record the partial melting and neocrystallization of magnetic grains in SBG during the thermal treatments required by the Thellier method, resulting in paleointensity values biased to low values. We further propose that this process is pronounced in Cretaceous and Jurassic SBG (relative to Holocene SBG) because devitrification on geologic time scales (i.e., tens of millions of years) lowers the transition temperature at which the neocrystallization can commence. Magnetic hysteresis monitoring may provide a straightforward means of detecting the formation of new magnetic inclusions in SBG during Thellier experiments.
Uma leitura econômica de O cortiço, de Aluísio Azevedo

This essay reexamines the novel O cortico [The Slum], by AluisioAzevedo, considering the new economic criticism, which hasemerged in the field of literary studies in the last decades. Theauthor of the article is interested in shedding light to the theme ofcapitalism development in the naturalist fiction, of the end of XIXcentury, to reflect on the present economical crisis that took placein 2008, and from which our society is still suffering its impact. Theessay focuses on fundamental principles to the development of thenovel’s main character, Joao Romao, such as greed, ethics, trust,speculation, as part of a capitalist project, tied at the same time, to aproject of modernity.
Angling management organizations: integrating the recreational sector into fishery management

Abstract This paper examines ways to reduce conflicts and improve the sustainability and value of marine recreational fisheries by fully integrating the recreational sector into the management of fisheries. One possibility involves a novel approach, here called angling management organizations (AMOs), which combines three of the more pervasive and promising trends in fishery management worldwide—management devolution, strengthened harvest rights, and co-management. AMOs are community-based organizations that are designed to conform to seven basic principles of integrated fishery management, which are described below. AMOs are loosely related to rights-based producer organizations in commercial fisheries, and are expected to strengthen resource stewardship, reduce enforcement and monitoring costs, alleviate management conflicts, and produce greater long-term net economic benefits in recreational fisheries. The other organizational structures considered here, including the management status quo, do not conform to all seven principles and are not expected to be as effective as AMOs.
Volatile Compounds Generated from Thermal Degradation of N-Acetylglucosamine

N-Acetylglucosamine was pyrolyzed at 200 °C for 30 min. Thermal degradation products were isolated and analyzed by GC and GC/MS. The volatile compounds that were identified included pyrazines, pyridines, pyrroles, and furans. The compound 3-acetamido-5-acetylfuran was found to be the major degradation product, with 2-acetylfuran, 3-acetamidofuran, pyrazine, pyridine, ethylpyrazine, methylpyrazine, 2-ethyl-6-methylpyrazine, 2,3-dimethylpyrazine, and acetamide in decreasing order. The compound 3-acetamido-5-acetylfuran was isolated by preparative column chromatography, and its NMR spectrum was obtained to confirm its structure. Keywords: N-Acetylglucosamine; glucosamine; chitin; chitosan; acetamido; acetylfuran
Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock.

Potassium channels closed by increases in intracellular ATP levels (KATP channels) have been described in vascular smooth muscle cells and other cell types. These channels are responsive to the metabolic state of the cells, and can be opened by a decrease in intracellular ATP levels and intra- or extracellular acidosis. Hemorrhagic shock is associated with early vasomotor paralysis as well as with early derangements in the intracellular metabolic status. Here we have tested whether activation of KATP channels contributes to the vasodilatation and early mortality in a rat model of severe hemorrhagic shock. In anesthetized rats hemorrhaged to a mean arterial blood pressure (MAP) of 35 mmHg, inhibition of KATP channels with glibenclamide or tolazamide (10 mg/kg i.v. bolus injection followed by an infusion of 10 mg/kg/h for 60 min), rapidly increased MAP and improved survival rate. The same dose of the KATP channel inhibitors did not cause a significant increase of MAP in animals not subjected to hemorrhage. The approach of inhibition of KATP channel activation in hemorrhagic shock is worthy of further investigations to determine whether it may represent a novel approach for early resuscitation during hemorrhage.