Investigation of the effect of pressure on metallurgical phenomena Final report, 20 Jun. 1960 - 30 Sep. 1965

Pressure effect on lead-thallium, tin telluride, and lead tellurid

Tests of the Kolmogorov-Smirnov type for exponential data with unknown scale, and related problems

SUMMARY Let D^, D^+ and D^− denote Kolmogorov-Smirnov typo one-sample statistics to test good ness of fit in the presence of unknown nuisance parameters; then the distributions of D^, D^+ and D^− depend on the population sampled and the estimator used. Simulation has been the primary tool for studying these statistics. Recently, Durbin obtained the distributions of D^, D^+ and D^− in terms of a Fourier transform for a wide class of underlying populations, and produced explicit results for the exponential case. In this paper, the distribution functions of D^, D^+ and D^− for the exponential case are derived from general results for order statistics, and computationally efficient approximations to these distribution functions are obtained. In the course of this derivation, Bonferroni inequalities of Kounias, and Sobel & Uppuluri are generalized. Certain problems of goodness-of-fit testing in the presence of nuisance parameters, whose solutions make use of existing tables, are also discussed. These problems include the Pareto, Rayleigh, power function, and uniform distribution

Predicting carcinogenicity by using batteries of dependent short-term tests.

Among the various methods for predicting carcinogenicity from a battery of short-term tests (STTs), the carcinogenicity prediction and battery selection (CPBS) procedure is the most prominent. A major assumption of CPBS is that the STTs used in the prediction are conditionally independent. Results of recent National Toxicology Program studies of four commonly used in vitro STTs contradict this assumption, thereby necessitating modification of CPBS to accommodate dependencies. This is accomplished via log-linear modeling, which then also yields an important dividend: standard errors for the predicted probabilities of carcinogenicity

Distribution of Time-Averaged Observables for Weak Ergodicity Breaking

We find a general formula for the distribution of time-averaged observables for systems modeled according to the sub-diffusive continuous time random walk. For Gaussian random walks coupled to a thermal bath we recover ergodicity and Boltzmann's statistics, while for the anomalous subdiffusive case a weakly non-ergodic statistical mechanical framework is constructed, which is based on L\'evy's generalized central limit theorem. As an example we calculate the distribution of $\bar{X}$: the time average of the position of the particle, for unbiased and uniformly biased particles, and show that $\bar{X}$ exhibits large fluctuations compared with the ensemble average $$.Comment: 5 pages, 2 figure

Patterns of Amino Acid Variability in NSI-like and SI-like V3 Sequences and a Linked Change in the CD4-Binding Domain of the HIV-1 Env Protein

The V3 domain plays a central role in the biology of the HIV-1 Env glycoprotein gp 120 as a dominant target for neutralizing antibodies for some HIV-1 isolates, and as a major determinant in the switch from the nonsyncytium-inducing (NSI) to the syncytium-inducing (SI) form of HIV-1 that is associated with accelerated disease progression. Basic amino acid substitutions are known to play an important role in the SI phenotype. We have used the presence of basic amino acid substitutions in V3 sequences to divide sequences in a large data base into SI-like and NSI-like. We found significant differences in features of sequence variability between these two groups of sequences. Of the thirty-six most frequent substitutions in V3, twenty appear disproportionately among either the SI-like sequences or the NSI-like sequences. The fourteen favored substitutions among the SI-like sequences account for 50% of the twofold increased variability seen in this group. In addition, we found a linked change within the CD4-binding domain of gp 120 downstream of V3. These differences are interpreted in the context of structure, function, and selective pressure. An understanding of these patterns of sequence variability offers the possibility of designing a degenerate SI-specific V3 immunogen to use as a therapeutic vaccine with the hope of slowing or preventing the appearance of SI variants

Superaging correlation function and ergodicity breaking for Brownian motion in logarithmic potentials

We consider an overdamped Brownian particle moving in a confining asymptotically logarithmic potential, which supports a normalized Boltzmann equilibrium density. We derive analytical expressions for the two-time correlation function and the fluctuations of the time-averaged position of the particle for large but finite times. We characterize the occurrence of aging and nonergodic behavior as a function of the depth of the potential, and support our predictions with extensive Langevin simulations. While the Boltzmann measure is used to obtain stationary correlation functions, we show how the non-normalizable infinite covariant density is related to the super-aging behavior.Comment: 16 pages, 6 figure

Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients.

BACKGROUND: Individual functional system scores (FSS) of the Expanded Disability Status Scale (EDSS) play a central role in determining the overall EDSS score in patients with early-stage multiple sclerosis (MS). Alemtuzumab treatment improves preexisting disability for many patients; however, it is unknown whether improvement is specific to certain functional systems. OBJECTIVE: We assessed the effect of alemtuzumab on individual FSS of the EDSS. METHODS: CAMMS223 was a 36-month, rater-blinded, phase 2 trial; treatment-naive patients with active relapsing-remitting MS, EDSS ≤3, and symptom onset within 3 years were randomized to annual courses of alemtuzumab or subcutaneous interferon beta-1a (SC IFNB-1a) 44 μg three times weekly. RESULTS: Alemtuzumab-treated patients had improved outcomes versus SC IFNB-1a patients on most FSS at Month 36; the greatest effect occurred for sensory, pyramidal, and cerebellar FSS. Among patients who experienced 6-month sustained accumulation of disability, clinical worsening occurred most frequently in the brainstem and sensory systems. For patients with 6-month sustained reduction in preexisting disability, pyramidal and sensory systems contributed most frequently to clinical improvement. CONCLUSIONS: Alemtuzumab demonstrated a broad treatment effect in improving preexisting disability. These findings may influence treatment decisions in patients with early, active relapsing-remitting MS displaying neurological deficits. ClinicalTrials.gov Identifier NCT00050778.Funding was provided by Sanofi Genzyme and Bayer Healthcare Pharmaceuticals. The authors would like to thank Marco Rizzo and Isabel Firmino for reviewing and providing input on the manuscript; Isabel Firmino is an employee of Sanofi Genzyme; Marco Rizzo was an employee of Sanofi Genzyme at the time the work was conducted. Data analysis was carried out by Linda Kasten, PROMETRIKA, LLC, Cambridge, MA, USA, which was supported by Sanofi Genzyme. Editorial support for this manuscript was provided by Fiona Nitsche, PhD, and Susan M Kaup, PhD, which was funded by Sanofi Genzyme. Fiona Nitsche is an employee of Evidence Scientific Solutions; Susan M Kaup was an employee of Evidence Scientific Solutions at the time the work was conducted.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jns.2016.02.02