One of These Things Is Not Quite the Same: A Comparison of the Patent Doctrine of Equivalents with Suitability for Filing an Abbreviated New Drug Application

The doctrine of equivalents as applied to chemical patents is compared to the FDA’s findings of bioequivalence in reviewing suitability petitions for filing Abbreviated New Drug Applications (ANDAs). The doctrine of equivalents provides the greatest flexibility early in the drug-development process, gradually diminishing as the product refinements become increasingly minor. Determinations of bioequivalence, however, exhibit the reverse trend as applied to analogous situations in the context of suitability petitions

Analysis of the Apollo heat shield performance. Volume 2 - CHAD computer program

CHAD computer program for Apollo heat shield ablation performance analysi

Systematic alteration of ATAC-seq for profiling open chromatin in cryopreserved nuclei preparations from livestock tissues.

The use of Assay for Transposase-Accessible Chromatin (ATAC-seq) to profile chromatin accessibility has surged over the past years, but its applicability to tissues has been very limited. With the intent of preserving nuclear architecture during long-term storage, cryopreserved nuclei preparations from chicken lung were used to optimize ATAC-seq. Sequencing data were compared with existing DNase-seq, ChIP-seq, and RNA-seq data to evaluate library quality, ultimately resulting in a modified ATAC-seq method capable of generating high quality chromatin accessibility data from cryopreserved nuclei preparations. Using this method, nucleosome-free regions (NFR) identified in chicken lung overlapped half of DNase-I hypersensitive sites, coincided with active histone modifications, and specifically marked actively expressed genes. Notably, sequencing only the subnucleosomal fraction dramatically improved signal, while separation of subnucleosomal reads post-sequencing did not improve signal or peak calling. The broader applicability of this modified ATAC-seq technique was tested using cryopreserved nuclei preparations from pig tissues, resulting in NFR that were highly consistent among biological replicates. Furthermore, tissue-specific NFR were enriched for binding motifs of transcription factors related to tissue-specific functions, and marked genes functionally enriched for tissue-specific processes. Overall, these results provide insights into the optimization of ATAC-seq and a platform for profiling open chromatin in animal tissues

An Hedonic Analysis of the Effects of Lake Water Clarity on New Hampshire Lakefront Properties

Policy makers often face the problem of evaluating how water quality affects a region's economic well-being. Using water clarity as a measure of the degree of eutrophication levels (as a lake becomes inundated with nutrients, water clarity decreases markedly), analysis is performed on sales data collected over a six-year period. Our results indicate that water clarity has a significant effect on prices paid for residential properties. Effects of a one-meter change in clarity on property value are also estimated for an average lake in four real estate market areas in New Hampshire, with effects differing substantially by area. Our findings provide state and local policy makers a measure of the cost of water quality degradation as measured by changes in water clarity, and demonstrate that protecting water quality may have a positive effect on property tax revenues.Resource /Energy Economics and Policy,

Analysis of the Apollo heat shield performance. Volume 1 - Analytical methods

Analysis of Apollo heat shield using mathematical model

Punctuated Equilibrium in Software Evolution

The approach based on paradigm of self-organized criticality proposed for experimental investigation and theoretical modelling of software evolution. The dynamics of modifications studied for three free, open source programs Mozilla, Free-BSD and Emacs using the data from version control systems. Scaling laws typical for the self-organization criticality found. The model of software evolution presenting the natural selection principle is proposed. The results of numerical and analytical investigation of the model are presented. They are in a good agreement with the data collected for the real-world software.Comment: 4 pages, LaTeX, 2 Postscript figure

Microarray screening of Guillain-Barré syndrome sera for antibodies to glycolipid complexes

Objective: To characterize the patterns of autoantibodies to glycolipid complexes in a large cohort of Guillain-Barré syndrome (GBS) and control samples collected in Bangladesh using a newly developed microarray technique. Methods: Twelve commonly studied glycolipids and lipids, plus their 66 possible heteromeric complexes, totaling 78 antigens, were applied to polyvinylidene fluoride–coated slides using a microarray printer. Arrays were probed with 266 GBS and 579 control sera (2 μL per serum, diluted 1/50) and bound immunoglobulin G detected with secondary antibody. Scanned arrays were subjected to statistical analyses. Results: Measuring antibodies to single targets was 9% less sensitive than to heteromeric complex targets (49.2% vs 58.3%) without significantly affecting specificity (83.9%–85.0%). The optimal screening protocol for GBS sera comprised a panel of 10 glycolipids (4 single glycolipids GM1, GA1, GD1a, GQ1b, and their 6 heteromeric complexes), resulting in an overall assay sensitivity of 64.3% and specificity of 77.1%. Notable heteromeric targets were GM1:GD1a, GM1:GQ1b, and GA1:GD1a, in which exclusive binding to the complex was observed. Conclusions: Rationalizing the screening protocol to capture the enormous diversity of glycolipid complexes can be achieved by miniaturizing the screening platform to a microarray platform, and applying simple bioinformatics to determine optimal sensitivity and specificity of the targets. Glycolipid complexes are an important category of glycolipid antigens in autoimmune neuropathy cases that require specific analytical and bioinformatics methods for optimal detection

The impact of the demographic transition on dengue in Thailand: Insights from a statistical analysis and mathematical modeling

Background: An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Methods and Findings: Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Conclusions: Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon

Improvement of the Embarrassingly Parallel Search for Data Centers

International audienceWe propose an adaptation of the Embarrassingly Parallel Search (EPS) method for data centers. EPS is a simple but efficient method for parallel solving of CSPs. EPS decomposes the problem in many distinct subproblems which are then solved independently by workers. EPS performed well on multi-cores machines (40), but some issues arise when using more cores in a datacenter. Here, we identify the decomposition as the cause of the degradation and propose a parallel decomposition to address this issue. Thanks to it, EPS gives almost linear speedup and outperforms work stealing by orders of magnitude using the Gecode solver

A Study to Assess the United States Navy\u27s Explosive Ordinance Disposal Mobile Unit Two Emergency Medical Technician Program

Contributing goals are: 1. Determine if a difference in national curriculum standards has changed the scope of emergency medical training approved by certified EOD personnel; 2. Determine if a difference in national curriculum standards has changed the standard of emergency medical training approved by certified EOD personnel; 3. Identify the training strengths/weaknesses in the current EOD/EMT Program; 4. If any weaknesses are found, recommend for consideration a course of action for medical command personnel