M.C. Perry letter to Acting Sailing Master, George A. Prentiss. New York, 1834.

Master Commander M. C. Perry orders Acting Sailing Master George A. Prentiss to report to the Commanding Office of the Receiving Ships for performing duty on board that vessel, dated February 4, 1834.https://digitalcommons.wofford.edu/littlejohnmss/1207/thumbnail.jp

Computational expression deconvolution in a complex mammalian organ

BACKGROUND: Microarray expression profiling has been widely used to identify differentially expressed genes in complex cellular systems. However, while such methods can be used to directly infer intracellular regulation within homogeneous cell populations, interpretation of in vivo gene expression data derived from complex organs composed of multiple cell types is more problematic. Specifically, observed changes in gene expression may be due either to changes in gene regulation within a given cell type or to changes in the relative abundance of expressing cell types. Consequently, bona fide changes in intrinsic gene regulation may be either mimicked or masked by changes in the relative proportion of different cell types. To date, few analytical approaches have addressed this problem. RESULTS: We have chosen to apply a computational method for deconvoluting gene expression profiles derived from intact tissues by using reference expression data for purified populations of the constituent cell types of the mammary gland. These data were used to estimate changes in the relative proportions of different cell types during murine mammary gland development and Ras-induced mammary tumorigenesis. These computational estimates of changing compartment sizes were then used to enrich lists of differentially expressed genes for transcripts that change as a function of intrinsic intracellular regulation rather than shifts in the relative abundance of expressing cell types. Using this approach, we have demonstrated that adjusting mammary gene expression profiles for changes in three principal compartments – epithelium, white adipose tissue, and brown adipose tissue – is sufficient both to reduce false-positive changes in gene expression due solely to changes in compartment sizes and to reduce false-negative changes by unmasking genuine alterations in gene expression that were otherwise obscured by changes in compartment sizes. CONCLUSION: By adjusting gene expression values for changes in the sizes of cell type-specific compartments, this computational deconvolution method has the potential to increase both the sensitivity and specificity of differential gene expression experiments performed on complex tissues. Given the necessity for understanding complex biological processes such as development and carcinogenesis within the context of intact tissues, this approach offers substantial utility and should be broadly applicable to identifying gene expression changes in tissues composed of multiple cell types

A novel method for gene-specific enhancement of protein translation by targeting 5’UTRs of selected tumor suppressors

Background Translational control is a mechanism of protein synthesis regulation emerging as an important target for new therapeutics. Naturally occurring microRNAs and synthetic small inhibitory RNAs (siRNAs) are the most recognized regulatory molecules acting via RNA interference. Surprisingly, recent studies have shown that interfering RNAs may also activate gene transcription via the newly discovered phenomenon of small RNA-induced gene activation (RNAa). Thus far, the small activating RNAs (saRNAs) have only been demonstrated as promoter-specific transcriptional activators. Findings We demonstrate that oligonucleotide-based trans-acting factors can also specifically enhance gene expression at the level of protein translation by acting at sequence-specific targets within the messenger RNA 5’-untranslated region (5’UTR). We designed a set of short synthetic oligonucleotides (dGoligos), specifically targeting alternatively spliced 5’UTRs in transcripts expressed from the THRB and CDKN2A suppressor genes. The in vitro translation efficiency of reporter constructs containing alternative TRβ1 5’UTRs was increased by up to more than 55-fold following exposure to specific dGoligos. Moreover, we found that the most folded 5’UTR has higher translational regulatory potential when compared to the weakly folded TRβ1 variant. This suggests such a strategy may be especially applied to enhance translation from relatively inactive transcripts containing long 5’UTRs of complex structure. Significance This report represents the first method for gene-specific translation enhancement using selective trans-acting factors designed to target specific 5’UTR cis-acting elements. This simple strategy may be developed further to complement other available methods for gene expression regulation including gene silencing. The dGoligo-mediated translation-enhancing approach has the potential to be transferred to increase the translation efficiency of any suitable target gene and may have future application in gene therapy strategies to enhance expression of proteins including tumor suppressors

Structured Decompositions: Structural and Algorithmic Compositionality

We introduce structured decompositions: category-theoretic generalizations of many combinatorial invariants -- including tree-width, layered tree-width, co-tree-width and graph decomposition width -- which have played a central role in the study of structural and algorithmic compositionality in both graph theory and parameterized complexity. Structured decompositions allow us to generalize combinatorial invariants to new settings (for example decompositions of matroids) in which they describe algorithmically useful structural compositionality. As an application of our theory we prove an algorithmic meta theorem for the Sub_P-composition problem which, when instantiated in the category of graphs, yields compositional algorithms for NP-hard problems such as: Maximum Bipartite Subgraph, Maximum Planar Subgraph and Longest Path

Prescribing unproven cancer drugs: Physician perspectives on expanded access and right to try

BACKGROUND: For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards. METHODS: This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and RTT using convenience sampling. We conducted semi-structured interviews and qualitative analysis to identify emerging themes. RESULTS: Most oncologists were confused between the two pathways, had little familiarity with RTT, and had little knowledge about experimental medicine available through either pathway. Oncologists reported a preference of enrolling patients in clinical trials over off-trial preapproval pathways with scant data. As a result, oncologists revealed concerns over properly evaluating risks for their patients. CONCLUSION: Our findings suggest that neuro-oncologists need better resources and clearer mechanisms at their institutions to help navigate EAP and RTT in order to counsel patients interested in experimental medicine

THRB (Thyroid Hormone Receptor, Beta)

Review on THRB, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Quantum simulation of spin ordering with nuclear spins in a solid state lattice

An experiment demonstrating the quantum simulation of a spin-lattice Hamiltonian is proposed. Dipolar interactions between nuclear spins in a solid state lattice can be modulated by rapid radio-frequency pulses. In this way, the effective Hamiltonian of the system can be brought to the form of an antiferromagnetic Heisenberg model with long range interactions. Using a semiconducting material with strong optical properties such as InP, cooling of nuclear spins could be achieved by means of optical pumping. An additional cooling stage is provided by adiabatic demagnetization in the rotating frame (ADRF) down to a nuclear spin temperature at which we expect a phase transition from a paramagnetic to antiferromagnetic phase. This phase transition could be observed by probing the magnetic susceptibility of the spin-lattice. Our calculations suggest that employing current optical pumping technology, observation of this phase transition is within experimental reach.Comment: 11 pages, 3 figues; Published versio

Evolution of substrate-specific gene expression and RNA editing in brown rot wood-decaying fungi.

Fungi that decay wood have characteristic associations with certain tree species, but the mechanistic bases for these associations are poorly understood. We studied substrate-specific gene expression and RNA editing in six species of wood-decaying fungi from the 'Antrodia clade' (Polyporales, Agaricomycetes) on three different wood substrates (pine, spruce, and aspen) in submerged cultures. We identified dozens to hundreds of substrate-biased genes (i.e., genes that are significantly upregulated in one substrate relative to the other two substrates) in each species, and these biased genes are correlated with their host ranges. Evolution of substrate-biased genes is associated with gene family expansion, gain and loss of genes, and variation in cis- and trans- regulatory elements, rather than changes in protein coding sequences. We also demonstrated widespread RNA editing events in the Antrodia clade, which differ from those observed in the Ascomycota in their distribution, substitution types, and the genomic environment. Moreover, we found that substrates could affect editing positions and frequency, including editing events occurring in mRNA transcribed from wood-decay-related genes. This work shows the extent to which gene expression and RNA editing differ among species and substrates, and provides clues into mechanisms by which wood-decaying fungi may adapt to different hosts