The Power of Posner: A Study of Prestige and Influence in the Federal Judiciary

Some judges have a disproportionate influence over the American judiciary; existing research has shown Judge Richard Posner is one of those judges. Our goal was to identify and determine how Judge Posner’s influence has changed over time. To measure and track his influence, we collected and compared citation and invocation data from three distinct time frames. While these measurements are imperfect, they can help illustrate the level of influence and prestige Judge Posner enjoys. The existing literature led us to expect Judge Posner’s early citation rates to be low. After several years on the bench, the citation rates for each opinion should rise dramatically. By contrast, Judge Posner’s citation rates are exceptionally high from the outset while more recent opinions actually have lower citation rates

NF-kappaB-dependent regulation of the diagnostic marker CD10 and role of BCL-2 activity in histone deacetylase inhibitor-induced apoptosis in human B-lymphoma cell lines

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with multiple distinct molecular subtypes. Increased NF-κB activity and expression of the microRNA miR-155 (product of the BIC gene) are associated with one subtype, called the activated B-cell (ABC) subtype. It is shown here that induction of NF-κB activity leads to increased miR-155 expression, the levels of miR-155 in a panel of B-lymphoma cell lines correlate with increased NF-κB activity, and the NF-κB p50/p65 heterodimer binds to a specific DNA site in the BIC promoter. Also described is a regulatory network wherein NF-κB-dependent up-regulation of miR-155 leads to reduced PU.1 transcription factor expression and consequently reduced PU.1-driven expression of B-lymphoma marker CD10 in the human B-lymphoma cell line BJAB. Genetic variation in DLBCL can be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's) as a monotherapy or in combination with other vi agents. It is shown here that two pan-HDACi's, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Ectopic over-expression of antiapoptotic proteins BCL-2 and BCL-XL or the pro-apoptotic protein BIM in select DLBCL cell lines can confer further resistance or sensitivity, respectively, to HDACi treatment. Additionally, the BCL-2 family antagonist ABT-737 can increase the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including the HDACi-resistant SUDHL6 cell line. Moreover, one vorinostat-resistant variant of the HDACi-sensitive cell line SUDHL4 has increased expression of anti-apoptotic proteins BCL-XL and MCL-1 and decreased sensitivity to ABT-737, and a second such variant cell line has increased expression of anti-apoptotic protein MCL-1. These results suggest that the balance of anti- to pro-apoptotic BCL-2 family protein expression is important in determining the sensitivity of DLBCL cell lines to HDACi-induced apoptosis. Thus, the sensitivity of DLBCL cell lines to treatment with HDACi's appears to depend on the complex regulation of BCL-2 family members, suggesting that the response of a subset of DLBCL patients to HDACi treatment may benefit from co-treatment with BCL-2 antagonists

Classical Solutions of the Generalized Camassa-Holm Equation

In this poster, well-posedness in C^1(R) (a.k.a. classical solutions) for a generalized Camassa- Holm equation (g-kbCH) having (k + 1)-degree nonlinearities is explored. This result holds for the Camassa-Holm, the Degasperi-Procesi and the Novikov equations, which improves upon earlier results in Sobolev and Besov spaces

Illumina mate-paired DNA sequencing-library preparation using Cre-Lox recombination

Standard Illumina mate-paired libraries are constructed from 3- to 5-kb DNA fragments by a blunt-end circularization. Sequencing reads that pass through the junction of the two joined ends of a 3-5-kb DNA fragment are not easy to identify and pose problems during mapping and de novo assembly. Longer read lengths increase the possibility that a read will cross the junction. To solve this problem, we developed a mate-paired protocol for use with Illumina sequencing technology that uses Cre-Lox recombination instead of blunt end circularization. In this method, a LoxP sequence is incorporated at the junction site. This sequence allows screening reads for junctions without using a reference genome. Junction reads can be trimmed or split at the junction. Moreover, the location of the LoxP sequence in the reads distinguishes mate-paired reads from spurious paired-end reads. We tested this new method by preparing and sequencing a mate-paired library with an insert size of 3 kb from Saccharomyces cerevisiae. We present an analysis of the library quality statistics and a new bio-informatics tool called DeLoxer that can be used to analyze an IlluminaCre-Lox mate-paired data set. We also demonstrate how the resulting data significantly improves a de novo assembly of the S. cerevisiae genome

"If you don't believe it, it won't help you": use of bush medicine in treating cancer among Aboriginal people in Western Australia

<p>Abstract</p> <p>Background</p> <p>Little is known about the use of bush medicine and traditional healing among Aboriginal Australians for their treatment of cancer and the meanings attached to it. A qualitative study that explored Aboriginal Australians' perspectives and experiences of cancer and cancer services in Western Australia provided an opportunity to analyse the contemporary meanings attached and use of bush medicine by Aboriginal people with cancer in Western Australia</p> <p>Methods</p> <p>Data collection occurred in Perth, both rural and remote areas and included individual in-depth interviews, observations and field notes. Of the thirty-seven interviews with Aboriginal cancer patients, family members of people who died from cancer and some Aboriginal health care providers, 11 participants whose responses included substantial mention on the issue of bush medicine and traditional healing were selected for the analysis for this paper.</p> <p>Results</p> <p>The study findings have shown that as part of their healing some Aboriginal Australians use traditional medicine for treating their cancer. Such healing processes and medicines were preferred by some because it helped reconnect them with their heritage, land, culture and the spirits of their ancestors, bringing peace of mind during their illness. Spiritual beliefs and holistic health approaches and practices play an important role in the treatment choices for some patients.</p> <p>Conclusions</p> <p>Service providers need to acknowledge and understand the existence of Aboriginal knowledge (epistemology) and accept that traditional healing can be an important addition to an Aboriginal person's healing complementing Western medical treatment regimes. Allowing and supporting traditional approaches to treatment reflects a commitment by modern medical services to adopting an Aboriginal-friendly approach that is not only culturally appropriate but assists with the cultural security of the service.</p

Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway.

The ability to biosynthetically produce chemicals beyond what is commonly found in Nature requires the discovery of novel enzyme function. Here we utilize two approaches to discover enzymes that enable specific production of longer-chain (C5-C8) alcohols from sugar. The first approach combines bioinformatics and molecular modelling to mine sequence databases, resulting in a diverse panel of enzymes capable of catalysing the targeted reaction. The median catalytic efficiency of the computationally selected enzymes is 75-fold greater than a panel of naively selected homologues. This integrative genomic mining approach establishes a unique avenue for enzyme function discovery in the rapidly expanding sequence databases. The second approach uses computational enzyme design to reprogramme specificity. Both approaches result in enzymes with &gt;100-fold increase in specificity for the targeted reaction. When enzymes from either approach are integrated in vivo, longer-chain alcohol production increases over 10-fold and represents &gt;95% of the total alcohol products

Characterizing Global Ozonesonde Profile Variability from Surface to the UT/LS with a Clustering Technique and MERRA-2 Reanalysis

Our previous studies employing the self-organizing map (SOM) clustering technique to ozonesonde data have found significant links among meteorological and chemical regimes, and the shape of the ozone (O3) profile from the troposphere to the lower stratosphere. These studies, which focused on specific northern hemisphere mid-latitude geographical regions, demonstrated the advantages of SOM clustering by quantifying O3 profile variability and the O3/meteorological correspondence. We expand SOM to a global set of ozonesonde profiles spanning 1980-present from 30 sites to summarize the connections among O3 profiles, meteorology, and chemistry, using the Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2) reanalysis and other ancillary data. Four clusters of O3 mixing ratio profiles from the surface to the upper troposphere/lower stratosphere (UT/LS) are generated for each site, which show dominant profile shapes and typical seasonality (or lack thereof) that generally correspond to latitude (i.e. Tropical, Subtropical, Mid-Latitude, Polar). Examination of MERRA-2 output reveals a clear relationship among SOM clusters and covarying meteorological fields (geopotential height, potential vorticity, and tropopause height) for Polar and Mid-latitude sites. However, these relationships break down within +/-30 deg latitude. Carbon monoxide satellite data, along with velocity potential, a proxy for convection, calculated from MERRA-2 wind fields assist characterization of the Tropical and Subtropical sites, where biomass burning and convective transport linked to the Madden- Julian Oscillation (MJO) dominate O3 variability. In addition to geophysical characterization of O3 profile variability, these results can be used to evaluate chemical transport model output and satellite measurements of O3

Integrable Deformations from Twistor Space

Integrable field theories in two dimensions are known to originate as defect theories of 4d Chern-Simons and as symmetry reductions of the 4d anti-self-dual Yang-Mills equations. Based on ideas of Costello, it has been proposed in work of Bittleston and Skinner that these two approaches can be unified starting from holomorphic Chern-Simons in 6 dimensions. We provide the first complete description of this diamond of integrable theories for a family of deformed sigma models, going beyond the Dirichlet boundary conditions that have been considered thus far. Starting from 6d holomorphic Chern-Simons theory on twistor space with a particular meromorphic 3-form $\Omega$, we construct the defect theory to find a novel 4d integrable field theory, whose equations of motion can be recast as the 4d anti-self-dual Yang-Mills equations. Symmetry reducing, we find a multi-parameter 2d integrable model, which specialises to the $\lambda$-deformation at a certain point in parameter space. The same model is recovered by first symmetry reducing, to give 4d Chern-Simons with generalised boundary conditions, and then constructing the defect theory.Comment: 38 pages, 1 figur

Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development