The 1995-1996 Decline of R Coronae Borealis - High Resolution Optical Spectroscopy

A set of high-resolution optical spectra of RCrB acquired before, during, and after its 1995-1996 decline is discussed. All of the components reported from earlier declines are seen. This novel dataset provides new information on these components including several aspects not previously seen in declines of RCrB and other RCBs. In the latter category is the discovery that the decline's onset is marked by distortions of absorption lines of high-excitation lines, and quickly followed by emission in these and in low excitation lines. This 'photospheric trigger' implies that dust causing the decline is formed close to the star. These emission lines fade quickly. After 1995 November 2, low excitation narrow (FWHM ~12 km s-1) emission lines remain. These appear to be a permanent feature, slightly blue-shifted from the systemic velocity, and unaffected by the decline except for a late and slight decrease of flux at minimum light. The location of the warm, dense gas providing these lines is uncertain. Absorption lines unaffected by overlying sharp emission are greatly broadened, weakened, and red-shifted at the faintest magnitudes when scattered light from the star is a greater contributor than direct light transmitted through the fresh soot cloud. A few broad lines are seen at and near minimum light with approxiamately constant flux: prominent among these are the He I triplet series, Na I D, and [N II] lines. These lines are blue-shifted by about 30 km s(-1) relative to the systemic velocity with no change in velocity over the several months for whicht he lines were seen. It is suggested that these lines, especially the He I lines, arise from an accretion disk around an unseen compact companion, which may be a low-mass white dwarf. If so, R CrB is similar to the unusual post-AGB star 89 Her.Comment: 31 pages, 26 figure

The refined biomimetic NeuroDigm GEL™ model of neuropathic pain in a mature rat [version 2; referees: 1 approved, 2 approved with reservations]

Background: Many humans suffering with chronic neuropathic pain have no objective evidence of an etiological lesion or disease. Frequently their persistent pain occurs after the healing of a soft tissue injury. Based on clinical observations over time, our hypothesis was that after an injury in mammals the process of tissue repair could cause chronic neural pain. Our objectives were to create the delayed onset of neuropathic pain in rats with minimal nerve trauma using a physiologic hydrogel, and characterize the rats’ responses to known analgesics and a targeted biologic.   Methods: In mature male Sprague Dawley rats (age 9.5 months) a percutaneous implant of tissue-derived hydrogel was placed in the musculofascial tunnel of the distal tibial nerve. Subcutaneous morphine (3 mg/kg), celecoxib (10 mg/kg), gabapentin (25 mg/kg) and duloxetine (10 mg/kg) were each screened in the model three times each over 5 months after pain behaviors developed. Sham and control groups were used in all screenings. A pilot study followed in which recombinant human erythropoietin (200 units) was injected by the GEL™ neural procedure site.   Results: The GEL group gradually developed mechanical hypersensitivity lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses demonstrated profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months, p ≤ 0.001. Histology of the GEL group tibial nerve revealed a site of focal neural remodeling, with neural regeneration, as found in nerve biopsies of patients with neuropathic pain.   Conclusion: The refined NeuroDigm GEL™ model induces a neural response resulting in robust neuropathic pain behavior. The analgesic responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin at the ectopic neural lesion appears to alleviate the persistent pain behavior in the GEL™ model rodents

The polyphase resonant converter modulator for pulse power and plasma applications

This paper describes a new technique to generate high voltage pulses (100 kV and up) with high peak power (10 MW and up) and high average power (1 MW and up) from a low voltage input source (e.g. +/- 1.2 kV). This technology is presently being used to provide cathode pulse modulation for the Spallation Neutron Source (SNS) accelerator klystron RF amplifiers, which operate to 140 kV 11 MW peak power and 1.1 MW average power. The design of the modulator, referred to as the Polyphase Resonant Converter-Modulator takes advantage of high-power component advances, in response to the needs of the traction motor industry (in particular, railroad locomotives), such as Insulated Gate Bipolar Transistors (IGBT's) and self-clearing metallized hazy polypropylene capacitors. In addition, the use of amorphous nanocrystalline transformer core alloy permits high frequency voltage and current transformation with low loss and small size. Other unique concepts embodied in the converter-modulator topology are polyphase resonant voltage multiplication and resonant rectification. These techniques further reduce size and improve electrical efficiency. Because of the resonant conversion techniques, electronic 'crowbars' and other load protective networks are not required. A shorted load detunes the circuit resonance and little power transfer can occur. This yields a high-power, high-voltage system that is inherently self-protective. To provide regulated output voltages, Pulse Width Modulation (PWM) of the individual IGBT pulses is used. A Digital signal Processor (DSP) is used to control the IGBT's, with adaptive feed forward and feedback control algorithms that improve pulse fidelity. The converter-modulator has many attributes that make it attractive to various pulse power and plasma applications such as high power RF sources, neutral beam modulators, and various plasma applications. This paper will review the design as used for the SNS accelerator and speculate on related plasma applications

Collective Flow from the Intranuclear Cascade Model

The phenomenon of collective flow in relativistic heavy ion collisions is studied using the hadronic cascade model ARC. Direct comparison is made to data gathered at the Bevalac, for Au+Au at $p=1-2$ GeV/c. In contrast to the standard lore about the cascade model, collective flow is well described quantitatively without the need for explicit mean field terms to simulate the nuclear equation of state. Pion collective flow is in the opposite direction to nucleon flow as is that of anti-nucleons and other produced particles. Pion and nucleon flow are predicted at AGS energies also, where, in light of the higher baryon densities achieved, we speculate that equation of state effects may be observable.Comment: 9 pages, 2 figures include

Women bargaining with patriarchy in coastal Kenya:contradictions, creative agency and food provisioning

Gender analysts have long recognised that challenging existing patriarchal structures involves risks for women, who may lose both long-term support and protection from kin. However, understanding the specific ways in which they ‘bargain with patriarchy’ in particular contexts is relatively poorly understood. We focus on a Mijikenda fishing community in coastal Kenya to explore contradictions in gendered power relations and how women deploy these to reinterpret gendered practices without directly challenging local patriarchal structures. We argue that a more complex understanding of women’s creative agency can reveal both the value to women of culturally-specific gendered roles and responsibilities and the importance of subtle changes that they are able to negotiate in these. With reference to food provisioning, the analysis contributes to more nuanced understandings of gendered household food security and women’s creative approaches to maintaining long-term security in their lives

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding vascular disease, as maintenance of a cells' epigenetic profile is essential for maintaining cellular phenotype. Global hypomethylation of proliferating aortic SMCs and concomitant decrease of DNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by ‘genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2′-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P = 0.017, OR = 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex diseas

High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types

OBJECTIVE: To retrospectively determine the frequency of N-Methyl-D-Aspartate (NMDA) receptor (NMDAR) autoantibodies in patients with different forms of dementia. METHODS: Clinical characterization of 660 patients with dementia, neurodegenerative disease without dementia, other neurological disorders and age-matched healthy controls combined with retrospective analysis of serum or cerebrospinal fluid (CSF) for the presence of NMDAR antibodies. Antibody binding to receptor mutants and the effect of immunotherapy were determined in a subgroup of patients. RESULTS: Serum NMDAR antibodies of IgM, IgA, or IgG subtypes were detected in 16.1% of 286 dementia patients (9.5% IgM, 4.9% IgA, and 1.7% IgG) and in 2.8% of 217 cognitively healthy controls (1.9% IgM and 0.9% IgA). Antibodies were rarely found in CSF. The highest prevalence of serum antibodies was detected in patients with “unclassified dementia” followed by progressive supranuclear palsy, corticobasal syndrome, Parkinson’s disease-related dementia, and primary progressive aphasia. Among the unclassified dementia group, 60% of 20 patients had NMDAR antibodies, accompanied by higher frequency of CSF abnormalities, and subacute or fluctuating disease progression. Immunotherapy in selected prospective cases resulted in clinical stabilization, loss of antibodies, and improvement of functional imaging parameters. Epitope mapping showed varied determinants in patients with NMDAR IgA-associated cognitive decline. INTERPRETATION: Serum IgA/IgM NMDAR antibodies occur in a significant number of patients with dementia. Whether these antibodies result from or contribute to the neurodegenerative disorder remains unknown, but our findings reveal a subgroup of patients with high antibody levels who can potentially benefit from immunotherapy

Genetic Variation Shapes Protein Networks Mainly through Non-transcriptional Mechanisms

Variation in the levels of co-regulated proteins that function within networks in an outbred yeast population is not driven by variation in the corresponding transcripts

Differential Allelic Expression in the Human Genome: A Robust Approach To Identify Genetic and Epigenetic Cis-Acting Mechanisms Regulating Gene Expression

The recent development of whole genome association studies has lead to the robust identification of several loci involved in different common human diseases. Interestingly, some of the strongest signals of association observed in these studies arise from non-coding regions located in very large introns or far away from any annotated genes, raising the possibility that these regions are involved in the etiology of the disease through some unidentified regulatory mechanisms. These findings highlight the importance of better understanding the mechanisms leading to inter-individual differences in gene expression in humans. Most of the existing approaches developed to identify common regulatory polymorphisms are based on linkage/association mapping of gene expression to genotypes. However, these methods have some limitations, notably their cost and the requirement of extensive genotyping information from all the individuals studied which limits their applications to a specific cohort or tissue. Here we describe a robust and high-throughput method to directly measure differences in allelic expression for a large number of genes using the Illumina Allele-Specific Expression BeadArray platform and quantitative sequencing of RT-PCR products. We show that this approach allows reliable identification of differences in the relative expression of the two alleles larger than 1.5-fold (i.e., deviations of the allelic ratio larger than 60∶40) and offers several advantages over the mapping of total gene expression, particularly for studying humans or outbred populations. Our analysis of more than 80 individuals for 2,968 SNPs located in 1,380 genes confirms that differential allelic expression is a widespread phenomenon affecting the expression of 20% of human genes and shows that our method successfully captures expression differences resulting from both genetic and epigenetic cis-acting mechanisms