Diagnosis and treatment of fungal infections in lung transplant recipients

Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of chronic lung allograft dysfunction. Prompt diagnosis and treatment are imperative to limit allograft damage. This review article discusses incidence, risk factors, and symptoms with a specific focus on diagnostic and treatment strategies in the lung transplant population for fungal infections caused b

Floquet-Bloch Theory for Nonperturbative Response to a Static Drive

We develop the Floquet-Bloch theory of noninteracting fermions on a periodic lattice in the presence of a constant electric field. As long as the field lies along a reciprocal lattice vector, time periodicity of the Bloch Hamiltonian is inherited from the evolution of momentum in the Brillouin zone. The corresponding Floquet quasienergies yield the Wannier-Stark ladder with interband couplings included to all orders. These results are compared to perturbative results where the lowest-order interband correction gives the field-induced polarization shift in terms of the electric susceptibility. Additionally, we investigate electronic transport by coupling the system to a bath within the Floquet-Keldysh formalism. We then study the breakdown of the band-projected theory from the onset of interband contributions and Zener resonances in the band-resolved currents. In particular, we consider the transverse quantum-geometric response in two spatial dimensions due to the Berry curvature. In the strong-field regime, the semiclassical theory predicts a plateau of the geometric response as a function of field strength. Here, we scrutinize the conditions under which the semiclassical results continue to hold in the quantum theory.Comment: 15 + 8 pages, 12 + 1 figure

Feasibility of interleukin-6 receptor blockade in cardiac antibody-mediated rejection

BACKGROUND: Antibody-mediated rejection (AMR) remains a significant cause of heart transplant mortality with few effective therapies. METHODS: This study aimed to describe initial experience of using interleukin-6 receptor blockade with tocilizumab in the treatment of acute cardiac AMR at Barnes-Jewish Hospital/Washington University Transplant Center from July 2017 to May 2021 (n = 7). Clinical, echocardiographic, and serum alloantibody data were analyzed before and after treatment. RESULTS: All participants demonstrated marked improvement in functional status. Echocardiographic data following 4-6 mo of tocilizumab revealed significant improvements in biventricular systolic function for all participants. Consistent reductions in donor-specific HLA or angiotensin type I receptor antibodies were not observed, suggesting that tocilizumab may act downstream of antibody production. No patient experienced drug-related complications that necessitated discontinuation of therapy. CONCLUSIONS: These findings provide initial insights into the safety and efficacy of interleukin-6 receptor blockade in the treatment of cardiac AMR and support the design of larger prospective studies

Growth response to 4-hydroxy-l-threonine of Escherichia coli mutants blocked in vitamin B6 biosynthesis

AbstractMutants of Escherichia coli (pdx B and pdx C) which are blocked in the biosynthesis of pyridoxol (vitamin B6) showed a growth response to 4-hydroxy-l-threonine. This observation constitutes the first direct evidence in support of the view that 4-hydroxy-l-threonine is implicated in the biosynthesis of vitamin B6. 1-Aminopropan-2,3-diol, the decarboxylation product of 4-hydroxy-l-threonine, does not support the growth of these mutants. Deuterium from deuterium-labelled 1-aminopropan-2,3-diol was not incorporated into pyridoxol

Artificial Stupidity

Public debate about AI is dominated by Frankenstein Syndrome, the fear that AI will become superhuman and escape human control. Although superintelligence is certainly a possibility, the interest it excites can distract the public from a more imminent concern: the rise of Artificial Stupidity (AS). This article discusses the roots of Frankenstein Syndrome in Mary Shelley’s famous novel of 1818. It then provides a philosophical framework for analysing the stupidity of artificial agents, demonstrating that modern intelligent systems can be seen to suffer from ‘stupidity of judgement’. Finally it identifies an alternative literary tradition that exposes the perils and benefits of AS. In the writings of Edmund Spenser, Jonathan Swift and E.T.A. Hoffmann, ASs replace, enslave or delude their human users. More optimistically, Joseph Furphy and Laurence Sterne imagine ASs that can serve human intellect as maps or as pipes. These writers provide a strong counternarrative to the myths that currently drive the AI debate. They identify ways in which even stupid artificial agents can evade human control, for instance by appealing to stereotypes or distancing us from reality. And they underscore the continuing importance of the literary imagination in an increasingly automated society

An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics

BackgroundAn isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990.ResultsWe demonstrate that despite these B. anthracis features, the isolate is severely attenuated in a guinea pig model. This prompted whole genome sequencing and closure. The comparative analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b) CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15 other isolates; c) the genome of CDC 684 contains a large chromosomal inversion that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual spatial orientation of the origin of replication (ori) to the termination of replication (ter) from 180° in wild-type B. anthracis to 120° in CDC 684 and e) this isolate also has altered growth kinetics in liquid media.ConclusionsWe propose two alternative hypotheses explaining the attenuated phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter relationship in CDC 684 has altered its DNA replication and/or transcriptome processes resulting in altered growth kinetics and virulence capacity. Hypothesis 2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has altered the expression of a regulatory element or other genes necessary for virulence

Биогеохимия мерзлых толщ арктического побережья полуострова Гыдан

Biogeochemistry of permanently frozen deposits on the arctic shore of Gydan peninsula Core drilling was performed in four regions of arctic shore on Gydan peninsula. Complex laboratory analysis of cores allowed to characterize biochemistry of Gydan permafrost. These results are compared with data from other permafrost provinces and are applied for paleoreconstructions.В четырех районах арктического побережья полуострова Гыдан проведено колонковое бурение и отобраны керны мерзлых отложений. Комплекс лабораторных анализов впервые позволил дать биогеохимическую характеристику мерзлых толщ на Гыдане, сравнить полученные результаты с другими районами криолитозоны и применить их для палеореконструкций

Neptune to the Common-wealth of England (1652): the republican Britannia and the continuity of interests

In the seventeenth century, John Kerrigan reminds us, “models of empire did not always turn on monarchy”. In this essay, I trace a vision of “Neptune’s empire” shared by royalists and republicans, binding English national interest to British overseas expansion. I take as my text a poem entitled “Neptune to the Common-wealth of England”, prefixed to Marchamont Nedham’s 1652 English translation of Mare Clausum (1635), John Selden’s response to Mare Liberum (1609) by Hugo Grotius. This minor work is read alongside some equally obscure and more familiar texts in order to point up the ways in which it speaks to persistent cultural and political interests. I trace the afterlife of this verse, its critical reception and its unique status as a fragment that exemplifies the crossover between colonial republic and imperial monarchy at a crucial moment in British history, a moment that, with Brexit, remains resonant

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition

Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via genetic changes of Smoothened or other downstream Hedgehog components. Here, we overcome these resistance mechanisms by modulating GLI transcription via inhibition of BET bromodomain proteins. We show the BET bromodomain protein, BRD4, regulates GLI transcription downstream of SMO and SUFU and chromatin immunoprecipitation studies reveal BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagement of these sites upon treatment with JQ1, a small molecule inhibitor targeting BRD4. Globally, genes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1 treatment, supporting direct regulation of GLI activity by BRD4. Notably, patient- and GEMM-derived Hedgehog-driven tumors (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor) respond to JQ1 even when harboring genetic lesions rendering them resistant to Smoothened antagonists