Amount-dependent temporal discounting?

Amount-dependent temporal discounting has been demonstrated for human choice between outcomes differing in amount and delay. In the only study to date with non-humans, Grace reported no evidence for amount-dependent temporal discounting with pigeons in a concurrent-chains procedure. The present experiments repeated Grace's procedure but with modifications to enhance the discrimination between small and large magnitude outcomes. In Experiment 1, sensitivity of pigeons' initial-link choice to the terminal link delay ratio was greater with large reinforcer durations in the terminal links than with small reinforcer durations. This result is consistent with a greater rate of temporal discounting for larger reinforcers (the reverse of the result for humans), but can also be explained as enhanced discrimination of delay ratios with larger reinforcer durations. The results of a second experiment supported Grace's conclusion that amount-dependent temporal discounting does not characterize pigeons' choice in concurrent chains. Because reinforcer amount was held constant between choice alternatives in the present experiments and that of Grace, but varied in the human studies, our results question whether prior demonstrations of amount-dependent discounting reflect the effects of reinforcer delay or of reinforcer amount. Differences in the procedures used to study discounting in humans (titration procedures) and non-humans (concurrent chains) may contribute to the divergent results across species.     

Synthesis,characterization and antitumor activity of novel octahedral Pt(IV) complexes

Novel platinum(IV) complexes were synthesized having octahedral structure for new antitumor agents. The series of (1,4-butanediamine)Pt(IV) complexes of the type trans,cis-[PtA(2)Cl(2)(1,4-butanediamine)] (A=hydroxo 9, acetato 12, trifluoroacetato 13 as axial ligands) and trans-[PtA(2)(malonate)(1,4-butanediamine)] (A=hydroxo 16, acetato 17, trifluoroacetato 18) were synthesized and characterized by IR, NMR and elemental analysis. The molecular structures of 12, 13 and 18 have been determined by X-ray diffraction methods. The crystals are monoclinic, P2 1/c with a=21.165 (5), b=9.050 (3), c=15.293 (3) A, beta=103.89 (2) degrees and Z=8 for 12, a=10.178 (5), b=12.894 (9), c=12.182 (8) A, beta=91.01 (5) degrees and Z=4 for 13 and a=10.460 (5), b=11.199 (8), c=15.641 (7) A, beta=98.41 (5) degrees, Z=4 for 18. Three crystallographically independent molecules of 12, 13 and 18 have octahedral coordination around Pt(IV) cation. The trans,cis-[PtA(2)Cl(2)(1,4-butanediamine)] were prepared by acetylation or trifluoroacetylation of trans,cis-[Pt(OH)(2)Cl(2)(1,4-butanediamine)]. The trans-[PtA(2)malonate(1,4-butanediamine)] 17 and 18 was prepared by a similar method. The in vitro cytotoxicity of theses Pt(IV) complexes have been evaluated against 12 cancer cell lines assayed by MTS method. The IC(50) values of the compounds 12 and 13 were shown to be lower than those of cisplatin. The in vivo antitumor activity of the Pt(IV) complexes was evaluated using mice bearing L1210 leukemia, B16 melanoma and L1210/cis-DDP cancer animal models. The compound 18 was found to highest activity against cisplatin-resistant cancer cells, L1210/cis-DDP, in vivo.     

Light-dependent phagotrophy in the freshwater mixotrophic chrysophyte Dinobryon cylindricum

The mixotrophic (bacterivorous), freshwater chrysophyte Dinobryon cylindricum was cultured under a variety of light regimes and in bacterized and axenic cultures to investigate the role of phototrophy and phagotrophy for the growth of this alga. D. cylindricum was found to be an obligate phototroph. The alga was unable to survive in continuous darkness even when cultures were supplemented with high concentrations of bacteria, and bacterivory ceased in cultures placed in the dark for a period longer than one day. Axenic growth of the alga was poor even in an optimal light regime. Live bacteria were required for sustained, vigorous growth of the alga in the light. Carbon (C), nitrogen (N), and phosphorus (P) budgets determined for the alga during growth in bacterized cultures indicated that bacterial biomass ingested by the alga may have contributed up to 25% of the organic carbon budget of the alga. Photosynthesis was the source of most (75%) of the organic carbon of the alga. D. cylindricum populations survived but did not grow when cultured in a continuous low light intensity (30 E m^–2 sec^–1), or in a light intensity of 150 E m^–2 sec^–1 for only two hours each day. Net efficiency of incorporation of bacterial C, N, and P into algal biomass under these two conditions was zero (i.e., no net algal population growth). We conclude that the primary function of bacterivorous behavior in D. cylindricum may be to provide essential growth factor(s) or major nutrients for photosynthetic growth, or to allow for the survival of individuals during periods of very low light intensity or short photoperiod. Offprint requests to: David A. Caron     

Targeted delivery of compounds to Trypanosoma brucei using the melamine motif

There is an urgent need for the development of new drugs for the treatment of human African trypanosomiasis. The causative organism, Trypanosoma brucei, has been shown to have some unusual plasma membrane transporters, in particular the P2 aminopurine transporter and related permeases, which have been used for the selective targeting of trypanocidal compounds to the organism. In this paper, we report the addition of melamine-based P2-targeting motifs to three different classes of compound in order to try and improve activity through increased selective uptake. The classes reported here are fluoroquinolones, difluoromethylornithine and artesunate derivatives.     

Development and validation of a CO-C7 FE complex for biomechanical study

In this study, the digitized geometrical data of the embalmed skull and vertebrae (C0-C7) of a 68-year old male cadaver were processed to develop a comprehensive, geometrically accurate, nonlinear C0-C7 FE model. The biomechanical response of human neck under physiological static loadings, near vertex drop impact and rear-end impact (whiplash) conditions were investigated and compared with published experimental results. Under static loading conditions, the predicted moment-rotation relationships of each motion segment under moments in midsagittal plane and horizontal plane agreed well with experimental data. In addition, the respective predicted head impact force history and the S-shaped kinematics responses of head-neck complex under near-vertex drop impact and rear-end conditions were close to those observed in reported experiments. Although the predicted responses of the head-neck complex under any specific condition cannot perfectly match the experimental observations, the model reasonably reflected the rotation distributions among the motion segments under static moments and basic responses of head and neck under dynamic loadings. The current model may offer potentials to effectively reflect the behavior of human cervical spine suitable for further biomechanics and traumatic studies.     

Voluntarily controlled bi-stable slant perception of real and photographed surfaces

We have quantified voluntarily selected perceived slant of real trapezoidal surfaces (a 'reverse-perspective' scene) and their photographed counterparts (pictorial space). The surfaces were slanted about the vertical axis and observers estimated slant relative to the frontal plane. We were particularly interested in those cases in which binocular disparity and monocular perspective provided conflicting slant information. We varied the monocularly and binocularly specified surface slants independently across stimulus presentations. To eliminate texture and shading cues we used sand-blasted aluminium trapezoidal surfaces illuminated from all directions. When disparity-specified slant and perspective-specified slant were conflicting, observers were able to perceive the surfaces in two ways: they perceived either a trapezoid or a rectangle. Our main finding is twofold. First, when subjects chose to perceive the trapezoid, the slant estimates followed the disparity-predicted slant with only a slight underestimation, as if they selected a pure binocular representation of slant governed only by disparity. Second, when subjects chose to perceive the rectangle their estimates for real surfaces were similar to those for photographed surfaces, as if they selected a representation of slant governed by perspective foreshortening.     

Leukemia-specific siRNA delivery by immunonanoplexes consisting of anti-JL1 minibody conjugated to oligo-9 Arg-peptides

Targeted mRNA degradation by short interfering RNAs (siRNAs) offers a great potential to treat cancers. siRNA therapeutics for leukemias are, however, hindered by poor intracellular uptake, limited blood stability and nonspecific delivery. To solve these problems, we developed an anti-JL1 immunonanoplex (antibody-coupled nanocomplex) for siRNA delivery using anti-JL1 minibody (leukemia cell-specific minibody) conjugated to oligo-9-Arg peptide (9R) for effective siRNA delivery to leukemic cells. The anti-JL1 immunonanoplexes were able to deliver siRNA specifically to leukemic cells (CEM and Jurkat), but not to control cancer cells (H9). According to FACS and confocal microscopic analysis, siRNAs delivered by immunonanoplex particles were rapidly taken up by the JL1-positive cancer cells in 2 h. Furthermore, we showed that the anti-JL1 immunonanoplexes were effectively targeted to JL1-positive cells (CEM) inoculated in the mouse bone marrow. These results suggest that the anti-JL1 immunonanoplex is a powerful siRNA delivery system for human leukemia therapies.     

Mild Joint Symptoms Are Associated with Lower Risk of Falls than Asymptomatic Individuals with Radiological Evidence of Osteoarthritis

Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls. This study included 389 participants [229 fallers (≥2 falls or one injurious fall in the past 12 months), 160 non-fallers (no history of falls)], age (≥65 years) from a randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT). Physical function was assessed using Timed Up and Go (TUG) and Functional Reach (FR) tests. Knee and hip OA were diagnosed using three methods: Clinical, Radiological and Self-report. OA symptom severity was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The total WOMAC score was categorized to asymptomatic, mild, moderate and severe symptoms. Individuals with radiological OA and ‘mild’ overall symptoms on the WOMAC score had reduced risk of falls compared to asymptomatic OA [OR: 0.402(0.172–0.940), p = 0.042]. Individuals with clinical OA and ‘severe’ overall symptoms had increased risk of falls compared to those with ‘mild’ OA [OR: 4.487(1.883–10.693), p = 0.005]. In individuals with radiological OA, mild symptoms appear protective of falls while those with clinical OA and severe symptoms have increased falls risk compared to those with mild symptoms. Both relationships between OA and falls were not mediated by physical limitations. Larger prospective studies are needed for further evaluation.