Antiviral compounds and methods for treating infections caused by double-stranded DNA viruses

The present invention relates to polyamide compounds and their use in pharmaceutical compositions and in medical applications for the treatment of human papillomavirus infections and/or polyomavirus infections. For the most up-to-date information about these patents, including the availability of Certificates of Correction, be sure to check the United States Patent and Trademark Office\u27s free, publicly accessible database: Patent Public Search https://ppubs.uspto.gov/pubwebapp/static/pages/landing.htmlhttps://irl.umsl.edu/patents/1001/thumbnail.jp

SLUDGE BATCH 4: MODEL BASED ASSESSMENTS OF THE FEBRUARY 2007 SLUDGE PROJECTION

The Savannah River National Laboratory (SRNL) has developed, and continues to enhance, its integrated capability to evaluate the impact of proposed sludge preparation plans on the Defense Waste Processing Facility's (DWPF's) operation. One of the components of this integrated capability focuses on frit development which identifies a viable frit or frits for each sludge option being contemplated for DWPF processing. A frit is considered viable if its composition allows for economic fabrication and if, when it is combined with the sludge option under consideration, the DWPF property/composition models (the models of DWPF's Product Composition Control System (PCCS)) indicate that the combination has the potential for an operating window (a waste loading (WL) interval over which the sludge/frit glass system satisfies processability and durability constraints) that would allow DWPF to meet its goals for waste loading and canister production. This report documents the results of SRNL's efforts to identify candidate frit compositions and corresponding predicted operating windows (defined in terms of WL intervals) for the February 2007 compositional projection of Sludge Batch 4 (SB4) developed by the Liquid Waste Organization (LWO). The nominal compositional projection was used to assess projected operating windows (in terms of a waste loading interval over which all predicted properties were classified as acceptable) for various frits, evaluate the applicability of the 0.6 wt% SO{sub 4}{sup =} PCCS limit to the glass systems of interest, and determine the impact (or lack thereof) to the previous SB4 variability studies. It should be mentioned that the information from this report will be coupled with assessments of melt rate to recommend a frit for SB4 processing. The results of this paper study suggest that candidate frits are available to process the nominal SB4 composition over attractive waste loadings of interest to DWPF. Specifically, two primary candidate frits for SB4 processing, Frit 510 and Frit 418, have projected operating windows that should allow for successful processing at DWPF. While Frit 418 has been utilized at DWPF, Frit 510 is a higher B{sub 2}O{sub 3} based frit which could lead to improvements in melt rate. These frits provide relatively large operating windows and demonstrate robustness to possible sludge compositional variation while avoiding potential nepheline formation issues. In addition, assessments of SO{sub 4}{sup =} solubility indicate that the 0.6 wt% SO{sub 4}{sup =} limit in PCCS is applicable for the Frit 418 and the Frit 510 based SB4 glass systems

Control of Nepheline Crystallization in Nuclear Waste Glass

Abstract Glass frits with a high B 2 O 3 concentration have been designed which, when combined with high-alumina concentration nuclear waste streams, will form glasses with durabilities that are acceptable for repository disposal and predictable using a free energy of hydration model. Two glasses with nepheline discriminator values closest to 0.62 showed significant differences in normalized boron release between the quenched and heat treated versions of each glass. X-ray diffraction confirmed that nepheline crystallized in the glass with the lowest nepheline discriminator value, and nepheline may also exist in the second glass as small nanocrystals. The high-B 2 O 3 frit was successful in producing simulated waste glasses with no detectable nepheline crystallization at waste loadings of up to 45 wt%. The melt rate of this frit was also considerably better than other frits with increased concentrations of Na 2 O. Introduction High-level wastes, a legacy of Cold War production of nuclear materials for defense, are stored at several Department of Energy (DOE) facilities in the United States. These wastes, typically in the form of a sludge stored in underground tanks, are being vitrified with a glass frit or mined, glass-forming minerals to form a glass wasteform suitable for final disposal in the national repository. The waste glass must meet DOE requirements for durability, or resistance to chemical leaching in water at elevated temperatures, in order to be acceptable to the repository. A significant volume of these wastes has been identified as containing high concentrations of Al 2 O 3 and Na 2 O. Based on current blending and washing strategies, waste streams at the Savannah River Site (SRS) have been identified with Al 2 O 3 concentrations from 25 to 40 wt%. Concentrations in some wastes at Hanford are as high as 80 wt%. The combination of high Al 2 O 3 and Na 2 O concentrations in the waste, coupled with lower SiO 2 concentrations in the glass as waste loadings (WLs) increase, can lead to the crystallization of nepheline (NaAlSiO 4 ). The impact of crystallization, or devitrification, on the durability of the glass wasteform is dependent upon the type and extent of the crystalline phases that develop

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Genomics reveals historic and contemporary transmission dynamics of a bacterial disease among wildlife and livestock

Whole-genome sequencing has provided fundamental insights into infectious disease epidemiology, but has rarely been used for examining transmission dynamics of a bacterial pathogen in wildlife. In the Greater Yellowstone Ecosystem (GYE), outbreaks of brucellosis have increased in cattle along with rising seroprevalence in elk. Here we use a genomic approach to examine Brucella abortus evolution, cross-species transmission and spatial spread in the GYE. We find that brucellosis was introduced into wildlife in this region at least five times. The diffusion rate varies among Brucella lineages (∼3 to 8 km per year) and over time. We also estimate 12 host transitions from bison to elk, and 5 from elk to bison. Our results support the notion that free-ranging elk are currently a self-sustaining brucellosis reservoir and the source of livestock infections, and that control measures in bison are unlikely to affect the dynamics of unrelated strains circulating in nearby elk populations

A thermodynamic unification of jamming

Fragile materials ranging from sand to fire-retardant to toothpaste are able to exhibit both solid and fluid-like properties across the jamming transition. Unlike ordinary fusion, systems of grains, foams and colloids jam and cease to flow under conditions that still remain unknown. Here we quantify jamming via a thermodynamic approach by accounting for the structural ageing and the shear-induced compressibility of dry sand. Specifically, the jamming threshold is defined using a non-thermal temperature that measures the 'fluffiness' of a granular mixture. The thermodynamic model, casted in terms of pressure, temperature and free-volume, also successfully predicts the entropic data of five molecular glasses. Notably, the predicted configurational entropy avoids the Kauzmann paradox entirely. Without any free parameters, the proposed equation-of-state also governs the mechanism of shear-banding and the associated features of shear-softening and thickness-invariance.Comment: 16 pgs double spaced. 4 figure

PLUTONIUM FEED IMPURITY TESTING IN A LANTHANIDE BOROSILICATE (LABS) GLASS

A vitrification technology utilizing a lanthanide borosilicate (LaBS) glass is a viable option for dispositioning excess weapons-useable plutonium that is not suitable for processing into mixed oxide (MOX) fuel. A significant effort to develop a glass formulation and vitrification process to immobilize plutonium was completed in the mid-1990s. The LaBS glass formulation was found to be capable of immobilizing in excess of 10 wt % Pu and to be tolerant of a range of impurities. A more detailed study is now needed to quantify the ability of the glass to accommodate the anticipated impurities associated with the Pu feeds now slated for disposition. The database of Pu feeds was reviewed to identify impurity species and concentration ranges for these impurities. Based on this review, a statistically designed test matrix of glass compositions was developed to evaluate the ability of the LaBS glass to accommodate the impurities. Sixty surrogate LaBS glass compositions were prepared in accordance with the statistically designed test matrix. The heterogeneity (e.g. degree of crystallinity) and durability (as measured by the Product Consistency Test - Method A (PCT-A)) of the glasses were used to assess the effects of impurities on glass quality

Transcriptome analysis of grain development in hexaploid wheat

Background: Hexaploid wheat is one of the most important cereal crops for human nutrition. Molecular understanding of the biology of the developing grain will assist the improvement of yield and quality traits for different environments. High quality transcriptomics is a powerful method to increase this understanding. Results: The transcriptome of developing caryopses from hexaploid wheat ( Triticum aestivum, cv. Hereward) was determined using Affymetrix wheat GeneChip (R) oligonucleotide arrays which have probes for 55,052 transcripts. Of these, 14,550 showed significant differential regulation in the period between 6 and 42 days after anthesis ( daa). Large changes in transcript abundance were observed which were categorised into distinct phases of differentiation ( 6 - 10 daa), grain fill ( 12 - 21 daa) and desiccation/maturation ( 28 - 42 daa) and were associated with specific tissues and processes. A similar experiment on developing caryopses grown with dry and/or hot environmental treatments was also analysed, using the profiles established in the first experiment to show that most environmental treatment effects on transcription were due to acceleration of development, but that a few transcripts were specifically affected. Transcript abundance profiles in both experiments for nine selected known and putative wheat transcription factors were independently confirmed by real time RT-PCR. These expression profiles confirm or extend our knowledge of the roles of the known transcription factors and suggest roles for the unknown ones. Conclusion: This transcriptome data will provide a valuable resource for molecular studies on wheat grain. It has been demonstrated how it can be used to distinguish general developmental shifts from specific effects of treatments on gene expression and to diagnose the probable tissue specificity and role of transcription factors