Effects of positive reinforcement training for heifers on responses to a subcutaneous injection.

Cattle are subjected to routine procedures that require restraint and close contact to humans, which are both potentially aversive to the animal. Positive reinforcement training techniques may affect how animals perceive and respond to these procedures. The objectives of the current study were to describe a positive reinforcement regimen used to train cattle to stand still for a sham injection, and to assess the effects of this training on the responses to an actual injection. Eight "agency" heifers were trained, over an average of 85 ± 4.6 sessions, with positive reinforcement (i.e., animals received a grain reinforcer for desired behaviors) to enter a headlock, and they were habituated with counterconditioning and desensitization to a sham injection (i.e., animals were gradually exposed to the sensation of the sham injection, paired with access to grain). The headlock remained open at all times to allow heifers to leave. Eight "habituation" heifers were exposed to the treatment area and headlock for an equal number of sessions and duration as agency heifers, and 7 "naïve" heifers were provided no exposure to the treatment area. Once agency heifers tolerated the sham injection, all animals received a 1-mL subcutaneous injection of 0.9% NaCl while in the head lock (habituation and naïve heifers were locked in but agency heifers were free to withdraw). Immediate responses to the injection, starting with tenting of the skin, were video recorded and summarized as a reactivity score, which included the number of steps, head tosses, and backing-up movements; we also recorded the latency to approach the treatment area and headlock for 3 d after the injection. Of the agency heifers, 5 remained standing for the actual injection, whereas 3 heifers moved out of the headlock for a brief period (1, 3, and 5 s, respectively). Habituation heifers had a higher reactivity score [17.5 (10.5-28); median (IQR)] than agency [6 (2-13.5)] and naïve heifers [6 (5-7)]. Averaged over the 3 d after injection, agency heifers showed lower latencies to come to the treatment area [8.7 (7.2-24.2) s] than did habituation [50.5 (28-60) s] and naïve [53.7 (18-60) s] heifers. Agency heifers voluntarily entered the headlock within 1.3 (1-1.5) s but, with one exception, none of the other heifers did so within the allowed 15 s. These results indicate that dairy heifers can be trained with positive reinforcement and counterconditioning to voluntarily accept a painful procedure, and that training can reduce avoidance behaviors during and after the procedure.

Tolerance of exercise-induced pain at a fixed rating of perceived exertion predicts time trial cycling performance.

To compare the predictive capacity of experimental pain and exercised-induced pain (EIP) on exercise performance. Thirty-two recreationally active male (n = 23) and female (n = 9) participants were recruited. Participants completed measures of pain tolerance by cold pressor test (CPT), pain pressure threshold via algometry (PPT), and EIP tolerance using an RPE clamp trial. A VO2max test provided traditional predictors of performance [VO2max , gas-exchange threshold (GET), peak power output (PPO)]. Finally, participants completed a 16.1-km cycling time trial (TT). No correlation was found between experimental pain measures (CPT, PPT) and TT performance. However, there was a significant correlation between EIP tolerance and TT performance (R = -0.83, P < 0.01). Regression analysis for pain and physiological predictor variables (mean pain in CPT, PPT, EIP tolerance, VO2max , PPO, GET) revealed that a significant model (P < 0.01) emerged when only PPO (Adjusted R2  = 0.739) and EIP tolerance (ΔR2  = 0.075) were used to predict TT performance. These findings suggest that EIP tolerance is an important factor in endurance performance. However, PPT and CPT have limited ability to assess this relationship, and so their use in EIP research should be treated with caution.

New lithium metal polymer solid state battery for an ultrahigh energy: nano C-LiFePO4 versus nano Li1.2V3O8.

Novel lithium metal polymer solid state batteries with nano C-LiFePO4 and nano Li1.2V3O8 counter-electrodes (average particle size 200 nm) were studied for the first time by in situ SEM and impedance during cycling. The kinetics of Li-motion during cycling is analyzed self-consistently together with the electrochemical properties. We show that the cycling life of the nano Li1.2V3O8 is limited by the dissolution of the vanadium in the electrolyte, which explains the choice of nano C-LiFePO4 (1300 cycles at 100% DOD): with this olivine, no dissolution is observed. In combination with lithium metal, at high loading and with a stable SEI an ultrahigh energy density battery was thus newly developed in our laboratory.

The effect of trial familiarisation on the validity and reproducibility of a field-based self-paced VO2max test.

The self-paced maximal oxygen uptake (VO2max) test (SPV), which is based on the Borg 6-20 Ratings of Perceived Exertion (RPE) scale, allows participants to self-regulate their exercise intensity during a closed-loop incremental maximal exercise test. As previous research has assessed the utility of the SPV test within laboratory conditions, the purpose to this study was to assess the effect of trial familiarisation on the validity and reproducibility of a field-based, SPV test. In a cross-sectional study, fifteen men completed one laboratory-based graded exercise test (GXT) and three field-based SPV tests. The GXT was continuous and incremental until the attainment of VO2max. The SPV, which was completed on an outdoor 400m athletic track, consisted of five x 2 min perceptually-regulated (RPE11, 13, 15, 17 and 20) stages of incremental exercise. There were no differences in the VO2max reported between the GXT (63.5±10.1 ml·kg(-1)·min(-1)) and each SPV test (65.5±8.7, 65.4±7.0 and 66.7±7.7 ml·kg(-1)·min(-1) for SPV1, SPV2 and SPV3, respectively; P>.05). Similar findings were observed when comparing VO2max between SPV tests (P>.05). High intraclass correlation coefficients were reported between the GXT and the SPV, and between each SPV test (≥.80). Although participants ran faster and further during SPV3, a similar pacing strategy was implemented during all tests. This study demonstrated that a field-based SPV is a valid and reliable VO2max test. As trial familiarisation did not moderate VO2max values from the SPV, the application of a single SPV test is an appropriate stand-alone protocol for gauging VO2max.

Analysing experienced and inexperienced cyclists' attentional focus and self-regulatory strategies during varying intensities of fixed perceived effort cycling: A mixed method study.

Using a think aloud approach during fixed perceived effort exercise is a unique method to explore the decision-making processes that guide the self-regulation of perceived effort during endurance-based activity. In a two-part study, authors investigated the attentional focus and self-regulatory strategies associated with: Part A - perceived effort corresponding to (RPEGET) and above gas exchange threshold (RPE+15%GET); Part B - between experienced and inexperienced cyclists during fixed perceived effort cycling tasks. Eighteen (15 male, 3 female) healthy, active individuals completed three visits (visit 1 - ramped incremental test and familiarisation, visit 2 and 3-30-min fixed perceived effort cycling). During which, power output, heart rate, lactate, think aloud, and perceptual markers were taken. Random-intercepts linear mixed-effects models assessed the condition, time, and condition × time interactions on all dependent variables. Power output, heart rate, lactate and instances of internal sensory monitoring (t195=2.57,p=.011,ß=0.95[0.23,1.68]) and self-regulation (t195=4.14,p=.001,ß=1.69[0.89,2.49]) were significantly higher in the RPE+15%GET versus RPEGET trial. No significant differences between inexperienced and experienced cyclists for internal sensory monitoring (t196=-1.78,p=.095,ß=-1.73[-3.64,0.18]) or self-regulatory thoughts (t196=-0.39,p=.699,ß=-1.06[-6.32,4.21]) were noted but there were significant condition × time interactions for internal monitoring (t196=2.02,p=.045,ß=0.44[0.01,0.87]) and self-regulation (t196=3.45,p=.001,ß=0.85[0.37,1.33]). Seemingly, experienced athletes associatively attended to internal psychophysiological state and subsequently self-regulate their psychophysiological state at earlier stages of exercise than inexperienced athletes. This is the first study to exhibit the differences in attentional focus and self-regulatory strategies that are activated based on perceived effort intensity and experience level in cyclists.

External exercise information provides no immediate additional performance benefit to untrained individuals in time trial cycling.

OBJECTIVE: To determine the importance of the provision of external exercise information to the setting of the pacing strategy, in subjects unfamiliar with a cycling task. DESIGN: Twenty-two healthy, untrained cyclists (VO(2max), 50 ± 9 mL-(1)·kg-(1)·min-(1)) were randomly assigned to a control (CON) group or an experimental (EXP) group and two successive 4 km time trials (TT) were performed, separated by a 17 min recovery. The CON group received distance knowledge and distance feedback; the EXP group received neither, but knew that each TT was to be of the same distance. RESULTS: No significant difference in completion time (p>0.05) was observed between the groups for either time to complete TT one (TT1) (CON=443 ± 33 s versus EXP=471 ± 63 s) or time to complete TT two (time trial 2) (CON=461 ± 37 s versus EXP=501 ± 94 s). No significant difference in the final RPE was observed between groups. However, a significant interaction for RPE (rating of perceived exertion)×TT in the CON was observed (F7,70=5.32, p<0.05), with significantly higher RPE values in the final kilometre of TT2 (p<0.05). CONCLUSION: The lack of any performance improvement in either group, despite the differences in exercise information received, indicates both a reliance on the afferent feedback for setting a pacing strategy and slow learning effect from practice in subjects unfamiliar with the task. The modification in RPE profile observed in the CON, despite no performance improvement, suggests exercise perception based changes may pre-empt work rate based changes and thus not immediately translate to improved performance.

The effect of non-contingent and accurate performance feedback on pacing and time trial performance in 4-km track cycling.

OBJECTIVE: To determine whether the provision of comparative performance feedback during 4 km track cycling affects completion time. DESIGN: Five highly trained male cyclists first performed a baseline (BL) 4-km time trial (TT) on a velodrome track, followed by two further randomised 4-km TT, during which riders received either correct (COR) or non-contingent (FAL) feedback based on their BL performance. RESULTS: Participants completed the COR TT in a significantly faster time (t(4)=-3.10, p<0.05) than the FAL TT (341 (8) s vs 350 (12) s). Over the TT, a significant difference in mean speed was apparent between the two conditions (F(15,60)=1.95, p<0.05) on the second (t(4)=4.71, p<0.05), 15th (t(4)=3.45, p<0.05) and final lap (t(4)=3.30, p<0.05). CONCLUSION: The significant difference in completion time and pacing strategy between the two conditions suggests that accurate, comparative performance feedback is beneficial to performance, especially during the start and end of an exercise bout. The results support the previously unfounded assumption that performance feedback is advantageous during exercise and highlights the importance of an athlete's support team during an event.

Li2TiO3/Ni foam composite as high-performance electrode for energy storage and conversion.

Li2TiO3/Ni foam composites were prepared by a solid-state reaction process. They crystallized in the monoclinic Li2TiO3 structure with C2/c space group. SEM images show that the Li2TiO3 particles are monodispersed crystallites of average size 49 nm, infused into porous scaffold Ni foam. As an anode in lithium battery, the composite delivered a discharge capacity of 153 mAh g-1 in an aqueous electrolyte and retained 95% of its initial capacity after 30 cycles. Moreover, the Li2TiO3/Ni foam composite as a negative electrode of pseudo-supercapacitor delivered a specific capacitance of 593 F g-1 and retained 95% of its initial capacitance after 1000 cycles. The enhanced capacity of Li2TiO3/Ni composite is due to porous scaffold Ni foam, which provides high conductivity to the Li2TiO3 particles and high effective surface area for redox reactions. The performance of the Li2TiO3/Ni foam as an electrode material for both lithium-ion batteries (LIBs) and supercapacitors (SCs) shows that this composite is promising for energy storage devices.

Bilateral extracephalic transcranial direct current stimulation improves endurance performance in healthy individuals.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used to enhance endurance performance but its precise mechanisms and effects remain unknown. OBJECTIVE: To investigate the effect of bilateral tDCS on neuromuscular function and performance during a cycling time to task failure (TTF) test. METHODS: Twelve participants in randomized order received a placebo tDCS (SHAM) or real tDCS with two cathodes (CATHODAL) or two anodes (ANODAL) over bilateral motor cortices and the opposite electrode pair over the ipsilateral shoulders. Each session lasted 10 min and current was set at 2 mA. Neuromuscular assessment was performed before and after tDCS and was followed by a cycling time to task failure (TTF) test. Heart rate (HR), ratings of perceived exertion (RPE), leg muscle pain (PAIN) and blood lactate accumulation (ΔB[La-]) in response to the cycling TTF test were measured. RESULTS: Corticospinal excitability increased in the ANODAL condition (P < 0.001) while none of the other neuromuscular parameters showed any change. Neuromuscular parameters did not change in the SHAM and CATHODAL conditions. TTF was significantly longer in the ANODAL (P = 0.003) compared to CATHODAL and SHAM conditions (12.61 ± 4.65 min; 10.61 ± 4.34 min; 10.21 ± 3.47 min respectively), with significantly lower RPE and higher ΔB[La-] (P < 0.001). No differences between conditions were found for HR (P = 0.803) and PAIN during the cycling TTF test (P = 0.305). CONCLUSION: Our findings demonstrate that tDCS with the anode over both motor cortices using a bilateral extracephalic reference improves endurance performance.

Effect of a Mediterranean Type Diet on Inflammatory and Cartilage Degradation Biomarkers in Patients with Osteoarthritis.

OBJECTIVES: To investigate the effects of a Mediterranean type diet on patients with osteoarthritis (OA). PARTICIPANTS: Ninety-nine volunteers with OA (aged 31 - 90 years) completed the study (83% female). SETTING: Southeast of England, UK. DESIGN: Participants were randomly allocated to the dietary intervention (DIET, n = 50) or control (CON, n = 49). The DIET group were asked to follow a Mediterranean type diet for 16 weeks whereas the CON group were asked to follow their normal diet. MEASUREMENTS: All participants completed an Arthritis Impact Measurement Scale (AIMS2) pre-, mid- and post- study period. A subset of participants attended a clinic at the start and end of the study for assessment of joint range of motion, ROM (DIET = 33, CON = 28), and to provide blood samples (DIET = 29, CON = 25) for biomarker analysis (including serum cartilage oligomeric matrix protein (sCOMP) (a marker of cartilage degradation) and a panel of other relevant biomarkers including pro- and anti-inflammatory cytokines). RESULTS: There were no differences between groups in the response of any AIMS2 components and most biomarkers (p > 0.05), except the pro-inflammatory cytokine IL-1α, which decreased in the DIET group (~47%, p = 0.010). sCOMP decreased in the DIET group by 1 U/L (~8%, p = 0.014). There was a significant improvement in knee flexion and hip rotation ROM in the DIET group (p < 0.05). CONCLUSIONS: The average reduction in sCOMP in the DIET group (1 U/L) represents a meaningful change, but the longer term effects require further study.

FTIR features of lithium-iron phosphates as electrode materials for rechargeable lithium batteries.

The essential structural features of lithium-metal phosphates (LMP) have been studied using FTIR spectroscopy which is a sensitive tool to probe the local environment in the solid materials. Various LMP materials where M is iron have been investigated including phospho-olivine LiFePO(4), diphosphate LiFeP(2)O(7), Nasicon-type phosphate Li(3)Fe(2)(PO(4))(3) and dihydrate FePO(4).2H(2)O. Vitreous and amorphous materials are also considered. Analysis of internal and external modes of vibration allows to distinguish between the different phases and the type of cationic environment in the framework. Results corroborate the contribution of the main factors which are responsible for the complexity of the spectra, i.e. departure from ideal symmetry, interactions between polyhedra, bridging atoms and lattice distortion.

Transcranial direct current stimulation improves isometric time to exhaustion of the knee extensors.

Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. Nine subjects underwent a control (CON), placebo (SHAM) and two different tDCS montage sessions in a randomized design. In one tDCS session, the anodal electrode was placed over the left motor cortex and the cathodal on contralateral forehead (HEAD), while for the other montage the anodal electrode was placed over the left motor cortex and cathodal electrode above the shoulder (SHOULDER). tDCS was delivered for 10min at 2.0mA, after which participants performed an isometric time to exhaustion (TTE) test of the right knee extensors. Peripheral and central neuromuscular parameters were assessed at baseline, after tDCS application and after TTE. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle exercise-induced muscle pain (PAIN) were monitored during the TTE. TTE was longer and RPE lower in the SHOULDER condition (P<0.05). Central and peripheral parameters, and HR and PAIN did not present any differences between conditions after tDCS stimulation (P>0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability.

Possible crossover of a nonuniversal quantity at the upper critical dimension.

We report on a possible crossover of a nonuniversal quantity at the upper critical dimensionality in the field of percolation. Plotting recent estimates for site percolation thresholds of hypercubes in dimension 6 < or =d < or =13 against corresponding predictions from the Galam-Mauger (GM) formula p(c) = p(0) [(d-1) (q-1)](-a) d(b) for percolation thresholds, a significant departure of p(c) is observed for d > or =6 . This result is reminiscent of the crossover undergone by universal quantities in critical phenomena. For bond percolation, evidence of such a crossover of dimensionality would require an improvement of the GM formula to reach a relative error of typically 0.2%, while it is currently at 0.9% for hypercubes.

Influence of various extracellular matrix components on the behavior of cultured chick embryo dermal cells.

Dermal cells isolated from the back of 7-day chick embryos were cultured on homogeneous two-dimensional substrates consisting of one or two extracellular matrix components (type I, III or IV collagen, fibronectin and several glycosaminoglycans: hyaluronate, chondroitin-4, chondroitin-6, dermatan or heparan sulfate). The effect of these substrates on cell behavior was compared with that of culture dish polystyrene. Three parameters of cell behavior were examined: cell proliferation and patterning, spreading (cell surface) and locomotion (velocity and directionality). Data were collected by sequential microphotography and analyzed by computer assisted morphometry. Types I and III collagen, hyaluronate and heparan sulfate had a slowing down effect on cell proliferation and patterning. The inhibitory effect of type I collagen was also detected in mixtures with glycosaminoglycans. The other components had no effect. While the smallest spreading was observed on fibronectin substrate, the largest was recorded on chondroitin-6 sulfate and heparan sulfate. The slowest velocity of locomotion was measured on fibronectin, types I and IV collagen and a mixture of type I collagen and chondroitin-6 sulfate. The fastest speed was recorded on chondroitin-4 sulfate. These effects are discussed in view of our knowledge of the role of the dermis in the development of skin and cutaneous appendages, and in the light of the morphogenetically related microheterogeneous distribution of collagens, fibronectin and various glycosaminoglycans in the developing skin.

Synthesis and properties of some peptide analogues of actinomycin D.

Analogues of actinomycin D (AMD) were synthesized in which amino acid replacements were made at various sites in the peptide moieties. These include (i) replacement of both N-methylvalines by N-methylleucine, (ii) replacement of both sarcosines by N-[2-(methoxycarbonyl)ethyl]glycine, and (iii) replacement of one or both D-valines by D-threonine. The purpose of replacements ii and iii was to ascertain the effect upon biological activity of introducing a new side chain which could be functionalized to allow the attachment of carrier molecules such as antibodies. NMR data indicated that none of the analogues had solution conformations significantly different from that of AMD. Difference spectra with DNA revealed that replacement i enhanced binding while the other analogues bound less strongly to DNA. All the analogues had lower antimicrobial activities than AMD. In contrast, 5,5'-(MeLeu)2AMD displayed in vitro antitumor activity comparable with that of AMD at approximately 100-fold lower concentrations.

Self-immolative prodrugs: candidates for antibody-directed enzyme prodrug therapy in conjunction with a nitroreductase enzyme.

The synthesis and properties of some prodrug candidates for antibody-directed enzyme prodrug therapy (ADEPT) are described. These compounds have been designed to generate the corresponding active drug upon interaction with a bacterial nitroreductase that can be conjugated to antibodies that recognize tumor-selective antigens. The active drugs included in the study are actinomycin D, mitomycin C, doxorubicin, 4-[bis(2-chloroethyl)amino]aniline and 4-[bis(2-chloroethyl)amino]phenol. The prodrugs were all 4-nitrobenzyloxycarbonyl derivatives of these drugs, which upon enzymatic reduction, generated the drug through self-immolation of the 4-(hydroxyamino)benzyloxycarbonyl group. In the case of actinomycin D, the ratio of the dose required between drug and prodrug to give the same cytotoxicity was greater than 100. The prodrug was also much less toxic (20-100x) than actinomycin D to mice in vivo. Therefore this self-immolative prodrug has a potential application in the treatment of cancer using an ADEPT-type approach.

Antitumor agents. 155. Synthesis and biological evaluation of 3',6,7-substituted 2-phenyl-4-quinolones as antimicrotubule agents.

A series of 3',6,7-substituted 2-phenyl-4-quinolones were designed and synthesized as antimitotic antitumor agents. All compounds showed cytotoxic effects (log GI50 < or = -4.0; log drug molar concentration required to cause 50% inhibition) against the growth of a variety of human tumor cell lines, including those derived from solid tumors such as non-small cell lung, colon, central nervous system, ovary, prostate, and breast cancers, when evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. The most potent compound (26) demonstrated strong cytotoxic effects with GI50 values in the nanomolar or subnanomolar range in almost all the tumor cell lines. Compound 26 was also a potent inhibitor of tubulin polymerization and radiolabeled colchicine binding to tubulin, with activity comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.

Antitumor Agents. 211. Fluorinated 2-phenyl-4-quinolone derivatives as antimitotic antitumor agents.

Fluorinated 2-phenyl-4-quinolone derivatives were synthesized and evaluated in National Cancer Institute's 60 human tumor cell line in vitro screen. From the results, the ketone moiety plays an essential role in activity. Among the compounds tested, 2'-fluoro-6-pyrrol-2-phenyl-4-quinolone (13) exhibited the most potent cytotoxic activities (log GI(50) < -8.00) against renal and melanoma tumor cell lines. Compound 13 was also a potent inhibitor of tubulin polymerization (IC(50) = 0.46 microM) and of radiolabeled colchicine binding to tubulin, with activities comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.

Antitumor agents. 178. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization.

As part of our continuing search for potential anticancer drug candidates in the 2-aryl-1,8-naphthyridin-4(1H)-one series, we have synthesized two series of 3'-substituted 2-phenyl-1,8-naphthyridin-4(1H)-ones and 2-naphthyl-1,8-naphthyridin-4(1H)-ones. All compounds showed significant cytotoxic effects (log GI50 < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines of the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. All 3'-substituted compounds demonstrated strong cytotoxic effects in almost all tumor cell lines. Introduction of an aromatic ring at the 2'- and 3'-positions also generated compounds with potent antitumor activity. Incorporation of an aromatic ring at the 3'- and 4'-positions produced compounds with reduced activity. Interestingly, introduction of a halogen at the 3'-position yielded compounds with different selectivity for the tumor cell lines tested. All 3'-halogenated compounds (29-36) and compounds 38 and 42-44 were potent inhibitors of tubulin polymerization with activities nearly comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Active agents also inhibited the binding of [3H]colchicine to tubulin.