Animal Research: A Review of Developments, 1950–2000

The third phase of the animal research debate started around 1950. After World War II the government became a major sponsor of scientific research, including biomedical research. The budget of the National Institutes of Health (NIH) grew dramatically and has continued to grow, with a few minor retrenchment periods, up to the present time (see Figure 1). This growth led to an enormous expansion in publicly funded research. In the private sector, the discovery of penicillin and streptomycin led to a tremendous expansion in pharmaceutical research and in the size of the prescription drug industry. These expansions in government funding for biomedical research and in private-sector investment in drug discovery created an increase in demand for laboratory animals

The Animal Research Controversy: Protest, Process & Public Policy

The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups in the 1980s, it has become more vociferous and has shifted from a reactive defense to a proactive, aggressive offense.https://www.wellbeingintlstudiesrepository.org/ebooks/1001/thumbnail.jp

Functional Relaxation and Guided Imagery as Complementary Therapy in Asthma: A Randomized Controlled Clinical Trial

Background: Asthma is a frequently disabling and almost invariably distressing disease that has a high overall prevalence. Although relaxation techniques and hypnotherapeutic interventions have proven their effectiveness in numerous trials, relaxation therapies are still not recommended in treatment guidelines due to a lack of methodological quality in many of the trials. Therefore, this study aims to investigate the efficacy of the brief relaxation technique of functional relaxation (FR) and guided imagery (GI) in adult asthmatics in a randomized controlled trial. Methods: 64 patients with extrinsic bronchial asthma were treated over a 4-week period and assessed at baseline, after treatment and after 4 months, for follow-up. 16 patients completed FR, 14 GI, 15 both FR and GI (FR/GI) and 13 received a placebo relaxation technique as the control intervention (CI). The forced expiratory volume in the first second (FEV 1) as well as the specific airway resistance (sR(aw)) were employed as primary outcome measures. Results: Participation in FR, GI and FR/GI led to increases in FEV 1 (% predicted) of 7.6 +/- 13.2, 3.3 +/- 9.8, and 8.3 +/- 21.0, respectively, as compared to -1.8 +/- 11.1 in the CI group at the end of the therapy. After follow-up, the increases in FEV 1 were 6.9 +/- 10.3 in the FR group, 4.4 +/- 7.3 in the GI and 4.5 +/- 8.1 in the FR/GI, compared to -2.8 +/- 9.2 in the CI. Improvements in sR(aw) (% predicted) were in keeping with the changes in FEV 1 in all groups. Conclusions: Our study confirms a positive effect of FR on respiratory parameters and suggests a clinically relevant long-term benefit from FR as a nonpharmacological and complementary therapy treatment option. Copyright (C) 2009 S. Karger AG, Base

The Animal Research Controversy: Protest, Process & Public Policy

The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups in the 1980s, it has become more vociferous and has shifted from a reactive defense to a proactive, aggressive offense

Quantitative comparison of planar coded aperture imaging reconstruction methods

Imaging distributions of radioactive sources plays a substantial role in nuclear medicine as well as in monitoring nuclear waste and its deposit. Coded Aperture Imaging (CAI) has been proposed as an alternative to parallel or pinhole collimators, but requires image reconstruction as an extra step. Multiple reconstruction methods with varying run time and computational complexity have been proposed. Yet, no quantitative comparison between the different reconstruction methods has been carried out so far. This paper focuses on a comparison based on three sets of hot-rod phantom images captured with an experimental γ-camera consisting of a Tungsten-based MURA mask with a 2 mm thick 256 × 256 pixelated CdTe semiconductor detector coupled to a Timepix© readout circuit. Analytical reconstruction methods, MURA Decoding, Wiener Filter and a convolutional Maximum Likelihood Expectation Maximization (MLEM) algorithm were compared to data-driven Convolutional Encoder-Decoder (CED) approaches. The comparison is based on the contrast-to-noise ratio as it has been previously used to assess reconstruction quality. For the given set-up, MURA Decoding, the most commonly used CAI reconstruction method, provides robust reconstructions despite the assumption of a linear model. For single image reconstruction, however, MLEM performed best of all analytical reconstruction methods, but took on average 45 times longer than MURA Decoding. The fastest reconstruction method is the Wiener Filter with a run time 4.3 times faster compared to MURA Decoding and a mediocre quality. The CED with a specifically tailored training set was able to succeed the most commonly used MURA decoding on average by a factor between 1.37 and 2.60 and an equal run time

Evolution of the eyes of vipers with and without infrared-sensing pit organs

We examined lens and brille transmittance, photoreceptors, visual pigments, and visual opsin gene sequences of viperid snakes with and without infrared-sensing pit organs. Ocular media transmittance is high in both groups. Contrary to previous reports, small as well as large single cones occur in pit vipers. Non-pit vipers differ from pit vipers in having a twotiered retina, but few taxa have been examined for this poorly understood feature. All vipers sampled express rh1, sws1 and lws visual opsin genes. Opsin spectral tuning varies but not in accordance with the presence/absence of pit organs, and not always as predicted from gene sequences. The visual opsin genes were generally under purifying selection, with positive selection at spectral tuning amino acids in RH1 and SWS1 opsins, and at retinal pocket stabilization sites in RH1 or LWS (and without substantial differences between pit and nonpit vipers). Lack of evidence for sensory trade-off between viperid eyes (in the aspects examined) and pit organs might be explained by the high degree of neural integration of vision and infrared detection; the latter representing an elaboration of an existing sense with addition of a novel sense organ, rather than involving the evolution of a wholly novel sensory system

TCR-engineered T cells: a model of inducible TCR expression to dissect the interrelationship between two TCRs

TCR gene-modified T cells for adoptive therapy simultaneously express the transgenic (tg) TCR and the endogenous TCR which might lead to mispaired TCRs with harmful unknown specificity and to a reduced function of TCR-tg T cells. We generated dual TCR T cells in two settings in which either TCR was constitutively expressed by a retroviral promoter while the second TCR expression was regulable by a tet-on system. Constitutively expressed TCR molecules were reduced on the cell surface depending on the induced TCR expression leading to strongly hampered function. Besides that, using fluorescence resonance energy transfer (FRET) we detected mispaired TCR dimers and different pairing behaviors of individual TCR chains with a mutual influence on TCR chain expression. The loss of function and mispairing could not be avoided by changing the TCR expression level or by introduction of an additional cysteine bridge. However, in polyclonal T cells, optimized TCR formats (cysteineization, codon optimization) enhanced correct pairing and function. We conclude from our data that (i) the level of mispairing depends on the individual TCRs and is not reduced by increasing the level of one TCR, and (ii) modifications (cysteineization, codon optimization) improve correct pairing but do not completely exclude mispairing (cysteineization)

The magnetic phase diagram of underdoped YBa2Cu3Oy inferred from torque magnetization and thermal conductivity

Strong evidence for charge-density correlation in the underdoped phase of the cuprate YBa2Cu3Oy was obtained by nuclear magnetic resonance (NMR) and resonant x-ray scatter- ing. The fluctuations were found to be enhanced in strong magnetic fields. Recently, 3D (three dimensional) charge-density wave (CDW) formation with long-range order (LRO) was observed by x-ray diffraction in H >15 T. To elucidate how the CDW transition impacts the pair condensate, we have used torque magnetization to 45 T and thermal conductivity $\kappa_{xx}$ to construct the magnetic phase diagram in untwinned crystals with hole density p = 0.11. We show that the 3D CDW transitions appear as sharp features in the susceptibility and $\kappa_{xx}$ at the fields HK and Hp, which define phase boundaries in agreement with spectroscopic techniques. From measurements of the melting field Hm(T) of the vortex solid, we obtain evidence for two vortex solid states below 8 K. At 0.5 K, the pair condensate appears to adjust to the 3D CDW by a sharp transition at 24 T between two vortex solids with very different shear moduli. At even higher H (42 T) the second vortex solid melts to a vortex liquid which survives to fields well above 45 T. de Haas-van Alphen oscillations appear at fields 24-28 T, below the lower bound for the upper critical field Hc2.Comment: 7 pages, 8 figures; New version of previous posting, reporting torque measurements to 45 Tesla and final magnetic phase diagra

TCR-engineered T cells: a model of inducible TCR expression to dissect the interrelationship between two TCRs

TCR gene-modified T cells for adoptive therapy simultaneously express the transgenic (tg) TCR and the endogenous TCR which might lead to mispaired TCRs with harmful unknown specificity and to a reduced function of TCR-tg T cells. We generated dual TCR T cells in two settings in which either TCR was constitutively expressed by a retroviral promoter while the second TCR expression was regulable by a tet-on system. Constitutively expressed TCR molecules were reduced on the cell surface depending on the induced TCR expression leading to strongly hampered function. Besides that, using fluorescence resonance energy transfer (FRET) we detected mispaired TCR dimers and different pairing behaviors of individual TCR chains with a mutual influence on TCR chain expression. The loss of function and mispairing could not be avoided by changing the TCR expression level or by introduction of an additional cysteine bridge. However, in polyclonal T cells, optimized TCR formats (cysteineization, codon optimization) enhanced correct pairing and function. We conclude from our data that (i) the level of mispairing depends on the individual TCRs and is not reduced by increasing the level of one TCR, and (ii) modifications (cysteineization, codon optimization) improve correct pairing but do not completely exclude mispairing (cysteineization)