Janus configurations with SL(2,Z)-duality twists, Strings on Mapping Tori, and a Tridiagonal Determinant Formula

We develop an equivalence between two Hilbert spaces: (i) the space of states of $U(1)^n$ Chern-Simons theory with a certain class of tridiagonal matrices of coupling constants (with corners) on $T^2$; and (ii) the space of ground states of strings on an associated mapping torus with $T^2$ fiber. The equivalence is deduced by studying the space of ground states of $SL(2,Z)$-twisted circle compactifications of $U(1)$ gauge theory, connected with a Janus configuration, and further compactified on $T^2$. The equality of dimensions of the two Hilbert spaces (i) and (ii) is equivalent to a known identity on determinants of tridiagonal matrices with corners. The equivalence of operator algebras acting on the two Hilbert spaces follows from a relation between the Smith normal form of the Chern-Simons coupling constant matrix and the isometry group of the mapping torus, as well as the torsion part of its first homology group.Comment: 21 pages, typos correcte

Pathogenic alpha-synuclein aggregates preferentially bind to mitochondria and affect cellular respiration

Abstract Misfolded alpha-synuclein (αSyn) is a major constituent of Lewy bodies and Lewy neurites, which are pathological hallmarks of Parkinson’s disease (PD). The contribution of αSyn to PD is well established, but the detailed mechanism remains obscure. Using a model in which αSyn aggregation in primary neurons was seeded by exogenously added, preformed αSyn amyloid fibrils (PFF), we found that a majority of pathogenic αSyn (indicated by serine 129 phosphorylated αSyn, ps-αSyn) was membrane-bound and associated with mitochondria. In contrast, only a minuscule amount of physiological αSyn was mitochondrial bound. In vitro, αSyn PFF displayed a stronger binding to purified mitochondria than did αSyn monomer, revealing a preferential mitochondria binding by aggregated αSyn. This selective mitochondrial ps-αSyn accumulation was confirmed in other neuronal and animal αSyn aggregation models that do not require exogenously added PFF and, more importantly, in postmortem brain tissues of patients suffering from PD and other neurodegenerative diseases with αSyn aggregation (α-synucleinopathies). We also showed that the mitochondrial ps-αSyn accumulation was accompanied by defects in cellular respiration in primary neurons, suggesting a link to mitochondrial dysfunction. Together, our results show that, contrary to physiological αSyn, pathogenic αSyn aggregates preferentially bind to mitochondria, indicating mitochondrial dysfunction as the common downstream mechanism for α-synucleinopathies. Our findings suggest a plausible model explaining the formation and the peculiar morphology of Lewy body and reveal that disrupting the interaction between ps-αSyn and the mitochondria is a therapeutic target for α-synucleinopathies.https://deepblue.lib.umich.edu/bitstream/2027.42/148288/1/40478_2019_Article_696.pd

A case of recurrent epilepsy-associated rosette-forming glioneuronal tumor with anaplastic transformation in the absence of therapy.

Rosette-forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy-associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5-year-old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET-like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high-grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild-type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high-grade regions. By immunohistochemistry there was loss of nuclear alpha-thalassemia mental retardation syndrome, X-linked (ATRX) expression only in the high-grade region. Next-generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high-grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q-codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole-arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy

Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic

Importance The rapidly expanding novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has challenged the medical community to an unprecedented degree. Physicians and health care workers are at added risk of exposure and infection during the course of patient care. Because of the rapid spread of this disease through respiratory droplets, health care workers who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures, such as otolaryngologists–head and neck surgeons, are particularly at risk. A set of safety recommendations was created based on a review of the literature and communications with physicians with firsthand knowledge of safety procedures during the COVID-19 pandemic. Observations A high number of health care workers were infected during the first phase of the pandemic in the city of Wuhan, China. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for health care workers without jeopardizing the care of patients. The most common procedures related to the examination and treatment of upper aerodigestive tract diseases were reviewed. Each category was reviewed based on the potential risk imposed to health care workers. Specific recommendations were made based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in patients with COVID-19. Conclusions and Relevance Preserving a highly skilled health care workforce is a top priority for any community and health care system. Based on the experience of health care systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of health care workers could be greatly reduced while providing high levels of care. The provided recommendations, which may evolve over time, could be used as broad guidance for all health care workers who are involved in the care of patients with COVID-19

Branes, Rings and Matrix Models in Minimal (Super)string Theory

We study both bosonic and supersymmetric (p,q) minimal models coupled to Liouville theory using the ground ring and the various branes of the theory. From the FZZT brane partition function, there emerges a unified, geometric description of all these theories in terms of an auxiliary Riemann surface M_{p,q} and the corresponding matrix model. In terms of this geometric description, both the FZZT and ZZ branes correspond to line integrals of a certain one-form on M_{p,q}. Moreover, we argue that there are a finite number of distinct (m,n) ZZ branes, and we show that these ZZ branes are located at the singularities of M_{p,q}. Finally, we discuss the possibility that the bosonic and supersymmetric theories with (p,q) odd and relatively prime are identical, as is suggested by the unified treatment of these models.Comment: 72 pages, 3 figures, improved treatment of FZZT and ZZ branes, minor change

Truthmakers and modality

This paper attempts to locate, within an actualist ontology, truthmakers for modal truths: truths of the form or . In section 1 I motivate the demand for substantial truthmakers for modal truths. In section 2 I criticise Armstrong’s account of truthmakers for modal truths. In section 3 I examine essentialism and defend an account of what makes essentialist attributions true, but I argue that this does not solve the problem of modal truth in general. In section 4 I discuss, and dismiss, a theistic account of the source of modal truth proposed by Alexander Pruss. In section 5 I offer a means of (dis)solving the problem

S-Band Transponder Multi-Network Compatibility, Space Environment and Radiation Testing

This paper presents the development and testing of the Software Define Radio (SDR) transceiver to meet the emerging needs for SmallSat communication and navigation. Vulcan Wireless and NASA Goddard Space Flight Center (GSFC) collaborated in testing the Vulcan Wireless S-band SDR engineering model. Apart from testing, communication link analysis was performed for a Low Earth Orbit (LEO) 400 km scenario. The results of the compatibility, radiation, environmental testing, and link analysis are presented. Also, this paper reviews a set of SmallSat missions under development at NASA GSFC

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide

BACKGROUND: For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. METHODS: Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. CONCLUSION: These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored

D-brane Decay in Two-Dimensional String Theory

We consider unstable D0-branes of two dimensional string theory, described by the boundary state of Zamolodchikov and Zamolodchikov [hep-th/0101152] multiplied by the Neumann boundary state for the time coordinate $t$. In the dual description in terms of the $c=1$ matrix model, this D0-brane is described by a matrix eigenvalue on top of the upside down harmonic oscillator potential. As suggested by McGreevy and Verlinde [hep-th/0304224], an eigenvalue rolling down the potential describes D-brane decay. As the eigenvalue moves down the potential to the asymptotic region it can be described as a free relativistic fermion. Bosonizing this fermion we get a description of the state in terms of a coherent state of the tachyon field in the asymptotic region, up to a non-local linear field redefinition by an energy-dependent phase. This coherent state agrees with the exponential of the closed string one-point function on a disk with Sen's marginal boundary interaction for $t$ which describes D0-brane decay.Comment: 19 pages, harvmac, minor change