Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Springback analysis of thin rectangular bars of non-linear work-hardening materials under torsional loading

A theoretical analysis of the springback of narrow rectangular strips of non-linear work-hardening material under torsional loading has been carried out. This theoretical analysis is supported by experimental results for rectangular mild steel strips of different thicknesses and lengths. Finally an analytical generalized expression relating angle of twist to twisting moment and residual angle of twist per unit length for rectangular strips under plastic torsion is obtained in non-dimensionalized form. A comparison between the results obtained for bars of non- linear and linear work-hardening materials loaded under torsion is also made.     

Video compression using spatiotemporal regularity flow.

We propose a new framework in wavelet video coding to improve the compression rate by exploiting the spatiotemporal regularity of the data. A sequence of images creates a spatiotemporal volume. This volume is said to be regular along the directions in which the pixels vary the least, hence the entropy is the lowest. The wavelet decomposition of regularized data results in a fewer number of significant coefficients, thus yielding a higher compression rate. The directions of regularity of an image sequence depend on both its motion content and spatial structure. We propose the representation of these directions by a 3-D vector field, which we refer to as the spatiotemporal regularity flow (SPREF). SPREF uses splines to approximate the directions of regularity. The compactness of the spline representation results in a low storage overhead for SPREF, which is a desired property in compression applications. Once SPREF directions are known, they can be converted into actual paths along which the data is regular. Directional decomposition of the data along these paths can be further improved by using a special class of wavelet basis called the 3-D orthonormal bandelet basis. SPREF -based video compression not only removes the temporal redundancy, but it also compensates for the spatial redundancy. Our experiments on several standard video sequences demonstrate that the proposed method results in higher compression rates as compared to the standard wavelet based compression.     

Densification and Properties of α-Silicon Carbide

Densification of a-Sic powders with no premixed sintering aids (type 1) and with premixed B and C (type 2) was investigated by sintering them at 2150° to 2200°C for 30 min. Flexure strengths, Weibull moduli, and fracture flaws were characterized for type 2 α-SiC only. The results were compared with those for a state-of-the-art sintered a-Sic material.     

Groundwater and human development: challenges and opportunities in livelihoods and environment.

At less than 1000 km3/year, the world's annual use of groundwater is 1.5% of renewable water resource but contributes a lion's share of water-induced human welfare. Global groundwater use however has increased manifold in the past 50 years; and the human race has never had to manage groundwater use on such a large scale. Sustaining the massive welfare gains groundwater development has created without ruining the resource is a key water challenge facing the world today. In exploring this challenge, we have focused a good deal on conditions of resource occurrence but less so on resource use. I offer a typology of five groundwater demand systems as Groundwater Socio-ecologies (GwSE), each embodying a unique pattern of interactions between socio-economic and ecological variables, and each facing a distinct groundwater governance challenge. During the past century, a growing corpus of experiential knowledge has accumulated in the industrialized world on managing groundwater in various uses and contexts. A daunting global groundwater issue today is to apply this knowledge intelligently to by far the more formidable challenge that has arisen in developing regions of Asia and Africa, where groundwater irrigation has evolved into a colossal anarchy supporting billions of livelihoods but threatening the resource itself.     

Comparative immunoreactivity of CD-68 and HMB-45 in malignant melanoma, neural tumors and nevi

The monoclonal antibody CD 68 (KP 1) reacts with fibrohistiocytic and some epithelial neoplasms; its reactivity compared with that of HMB 45 in malignant melanoma (MM) and neural tumors needs further elucidation. Using a streptavidin-biotin-immunoperoxidase procedure, we examined the reactivity of 65 MM (46 conventional, 1 polypoid, 6 desmoplastic [DMM], and 12 metastatic), 21 neurofibromas, 1 neurofibrosarcoma, 10 schwannomas, 1 perineurioma, 2 neurothekeomas, and 14 blue and 26 other nevi for CD-68, HMB-45-defined antigen, S 100 and neurofilament protein. A positive staining for CD 68 was observed in 38 of 42 primary, 5 of 6 DMM, and 11 of 12 metastatic melanomas; 6 of 10 schwannomas; 5 of 10 nevi with junctional component and all 14 blue nevi. All 21 neurofibromas, 1 each neurofibrosarcoma and perineurioma, both neurothekeomas, and all 12 nevi with dermal component were CD 68-negative. HBM 45 was expressed by all 44 primary, none of 6 DMM, and 7 of 12 metastatic melanomas; by none of 10 schwannomas, 6 neurofibromas, 1 neurofibrosarcoma, 1 perineurioma and 2 neurothekeomas. Both junctional nevi, 8 of 10 nevi with junctional components, 1 of 10 dermal components of junctional nevi, and 11 of 13 blue nevi were also HMB 45 positive. Except for 1 perineurioma, S 100 decorated all tumors examined. NF was immunoreactive in 1 of 45 conventional melanomas, 2 of 21 neurofibromas, 2 of 10 schwannomas, and 3 of 10 blue nevi; it was non-reactive in all polypoid, desmoplastic and metastatic melanomas; neurofibrosarcoma, perineurioma, neurothekeoma and other nevi. We conclude that the CD-68-reactivity in primary melanomas, neurofibromas, neurofibrosarcomas, perineuriomas, and nevi was similar to that of HMB 45. The significantly higher CD 68-positivity than of HMB 45 in metastatic and desmoplastic melanomas and schwannomas may be of diagnostic value.     

Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets

The objectives of this work were to apply several profile comparison approaches to dissolution data of four different but bioequivalent metoprolol tartrate tablet formulations to (1) identify the advantages and disadvantages of each approach, (2) quantify the metric for comparing dissolution profiles of each method, (3) determine metric limits that are consistent with the observed bioequivalence, and (4) rationalize the observed metric limits with respect to the role of dissolution in overall metoprolol absorption. Dissolution was performed by the USP monograph method on four formulations of metoprolol tartrate tablets (Lopressor plus fast, medium, and slow dissolving test formulations). Three general approaches to compare dissolution profiles were examined; they were ANOVA-based, model-independent, and model-dependent approaches. It is concluded that model-independent approaches and several model-dependent approaches yielded numerical results that can serve as objective and quantitative metrics for comparing entire dissolution profiles of the four metoprolol tartrate formulations. However, these methods presented complications. Some metrics were dependent on the length of the dissolution profile and the sampling scheme. Results from the pairwise procedures also depended on the pairing assignment of individual profiles. In spite of complications, these methods suggested wide dissolution specification limits. Wide dissolution specifications were rationalized through an analysis of in vitro-in vivo relationships, which indicated metoprolol dissolution from these formulations was not the rate-limiting step; hence, a range of dissolution profiles can be expected to yield equivalent plasma profiles.     

Model concrete beam-column joints subjected to cyclic loading at two rates

Small-scale models of reinforced concrete beam-column joint were subjected to large cyclic displacements at two rates: 2.5×10⁻³ and 1.0 Hz. To assess damage, free-vibration tests were conducted. The reliability of the modelling techniques was established by comparison of the results for the slower rate with those obtained from the full-scale tests on prototype. The higher rate of loading caused a greater damage than that at the lower rate. This was evidenced by the measurements of the energy absorbed in the hysteresis loops, equivalent damping, and the stiffness and damping obtained from the free-vibration test. The relatively greater extent of damage appears to result from the different bond behaviour at different rates of loading.