Integrity testing of Planova™ BioEX virus removal filters used in the manufacture of biological products

AbstractConfirmation of virus filter integrity is crucial for ensuring the safety of biological products. Two main types of virus filter defects may produce inconsistent and undesirable performance in virus removal: improper pore-size distribution across the membrane; and specific damage, such as tears, broken fibers, or pinholes. Two integrity tests are performed on each individual filter manufactured by Asahi Kasei Medical to ensure the absence of these defects prior to shipment. In this study, we verified that typical usage of Planova™ BioEX filters would not improperly shift the pore-size distribution. Damage occurring during shipment and use (e.g., broken fibers or pinholes) can be detected by end-users with sufficient sensitivity using air–water diffusion based leakage tests. We prepared and tested filters with model pinhole defects of various sizes to develop standard acceptance criteria for the leakage test relative to porcine parvovirus infectivity logarithmic reduction values (LRVs). Our results demonstrate that pinhole defects at or below a certain size for each effective filter surface area have no significant impact on the virus LRV. In conclusion the leakage test is sufficiently sensitive to serve as the sole end-user integrity test for Planova™ BioEX filters, facilitating their use in biopharmaceuticals manufacturing

Comparison of low-pass filters for SPECT imaging

In single photon emission computed tomography (SPECT) imaging, the choice of a suitable filter and its parameters for noise reduction purposes is a big challenge. Adverse effects on image quality arise if an improper filter is selected. Filtered back projection (FBP) is the most popular technique for image reconstruction in SPECT. With this technique, different types of reconstruction filters are used, such as the Butterworth and the Hamming. In this study, the effects on the quality of reconstructed images of the Butterworth filter were compared with the ones of the Hamming filter. A Philips ADAC forte gamma camera was used. A low-energy, high-resolution collimator was installed on the gamma camera. SPECT data were acquired by scanning a phantom with an insert composed of hot and cold regions. A Technetium-99m radioactive solution was homogenously mixed into the phantom. Furthermore, a symmetrical energy window (20%) centered at 140 keV was adjusted. Images were reconstructed by the FBP method. Various cutoff frequency values, namely, 0.35, 0.40, 0.45, and 0.50 cycles/cm, were selected for both filters, whereas for the Butterworth filter, the order was set at 7. Images of hot and cold regions were analyzed in terms of detectability, contrast, and signal-to-noise ratio (SNR). The findings of our study indicate that the Butterworth filter was able to expose more hot and cold regions in reconstructed images. In addition, higher contrast values were recorded, as compared to the Hamming filter. However, with the Butterworth filter, the decrease in SNR for both types of regions with the increase in cutoff frequency as compared to the Hamming filter was obtained. Overall, the Butterworth filter under investigation provided superior results than the Hamming filter. Effects of both filters on the quality of hot and cold region images varied with the change in cutoff frequency

Simultaneous diagonalisation of the covariance and complementary covariance matrices in quaternion widely linear signal processing

Recent developments in quaternion-valued widely linear processing have established that the exploitation of complete second-order statistics requires consideration of both the standard covariance and the three complementary covariance matrices. Although such matrices have a tremendous amount of structure and their decomposition is a powerful tool in a variety of applications, the non-commutative nature of the quaternion product has been prohibitive to the development of quaternion uncorrelating transforms. To this end, we introduce novel techniques for a simultaneous decomposition of the covariance and complementary covariance matrices in the quaternion domain, whereby the quaternion version of the Takagi factorisation is explored to diagonalise symmetric quaternion-valued matrices. This gives new insights into the quaternion uncorrelating transform (QUT) and forms a basis for the proposed quaternion approximate uncorrelating transform (QAUT) which simultaneously diagonalises all four covariance matrices associated with improper quaternion signals. The effectiveness of the proposed uncorrelating transforms is validated by simulations on both synthetic and real-world quaternion-valued signals.Comment: 41 pages, single column, 10 figure

Photographic image enhancement

Deblurring capabilities would significantly improve the scientific return from Space Shuttle crew-acquired images of the Earth and the safety of Space Shuttle missions. Deblurring techniques were developed and demonstrated on two digitized images that were blurred in different ways. The first was blurred by a Gaussian blurring function analogous to that caused by atmospheric turbulence, while the second was blurred by improper focussing. It was demonstrated, in both cases, that the nature of the blurring (Gaussian and Airy) and the appropriate parameters could be obtained from the Fourier transformation of their images. The difficulties posed by the presence of noise necessitated special consideration. It was demonstrated that a modified Wiener frequency filter judiciously constructed to avoid over emphasis of frequency regions dominated by noise resulted in substantially improved images. Several important areas of future research were identified. Two areas of particular promise are the extraction of blurring information directly from the spatial images and improved noise abatement form investigations of select spatial regions and the elimination of spike noise

Test-aware combinatorial interaction testing

Combinatorial interaction testing (CIT) approaches system- atically sample a given configuration space and select a set of configurations, in which each valid t-way option setting combination appears at least once. A battery of test cases are then executed in the selected configurations. Exist- ing CIT approaches, however, do not provide a system- atic way of handling test-specific inter-option constraints. Improper handling of such constraints, on the other hand, causes masking effects, which in turn causes testers to de- velop false confidence in their test processes, believing them have tested certain option setting combinations, when they in fact have not. In this work, to avoid the harmful conse- quences of masking effects caused by improper handling of test-specific constraints, we compute t-way test-aware cov- ering arrays. A t-way test-aware covering array is not just a set of configurations as is the case in traditional covering arrays, but a set of configurations, each of which is asso- ciated with a set of test cases. We furthermore present a set of empirical studies conducted by using two widely-used highly-configurable software systems as our subject applica- tions, demonstrating that test-specific constraints are likely to occur in practice and the proposed approach is a promis- ing and effective way of handling them

Retention and application of Skylab experiences to future programs

The problems encountered and special techniques and procedures developed on the Skylab program are described along with the experiences and practical benefits obtained for dissemination and use on future programs. Three major topics are discussed: electrical problems, mechanical problems, and special techniques. Special techniques and procedures are identified that were either developed or refined during the Skylab program. These techniques and procedures came from all manufacturing and test phases of the Skylab program and include both flight and GSE items from component level to sophisticated spaceflight systems