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The optoelectronic properties of functionalized graphene quantum dots (GQDs) have been explored by simulating electronic structure of three different shapes of GQDs containing exclusively zigzag or armchair edges in both pristine and functionalized forms. Absorption spectra and transition densities for the low-lying excited states are evaluated by using time-dependent density functional theory and compared for different functionalization species. The functionalization position dictates the optical properties of square GQDs, where isomers with CH

In her dedicated promotion of feminism and pacifism, especially during the 1930s, Vera Brittain (1893–1970) was strongly influenced by Ber­trand Russell’s writings, especially Marriage and Morals (1929) and Which Way to Peace? (1936). Both were members of the Peace Pledge Union, and she continued as a sponsor after Russell abandoned his pac­ifism soon after the beginning of the Second World War. She admired his political and social activism in the aftermath of that war, endorsing it as much as her family situation allowed; and, as chairman of the Peace News board, Brittain intervened in Russell’s support when a dispute broke out between him and the editor. Although their rela­tionship was personally limited, Russell’s influence on her opinions and actions was profound.

Post activation potentiation (PAP) is an acute enhancement of muscular function subsequent to an intense muscle conditioning activity. Practical application of PAP as a physical preparation for enhanced performance is a topic of considerable interest in the sport performance community. The purpose of this study was to determine if a dynamic warm-up (WU) plus a progression of deadlift (DL) sets culminating in a one-repetition maximum DL (1-RM DL) (i.e., a PAP conditioning activity) is more effective in improving the standing long jump (SLJ) as opposed to using a dynamic WU alone. Secondarily, it was of interest to determine if there was a meaningful relationship between the 1-RM DL and SLJ ability. Twenty NCAA Division I male North American football players participated in the study (age=20.3±2.3 years, height=183.5±6.3 cm, mass=96.3±17.1 kg). Participants met three times separated by one week. The initial gathering was an orientation meeting where participants were briefed on the study protocol and height, age and body mass were recorded. During the first data collection the participants completed a dynamic WU immediately followed by a progression of DLs culminating in a 1-RM DL; this served as a PAP conditioning activity. Following the PAP WU (5-6 minutes) the participants completed two trials of SLJs separated by 2-3 minutes. During the second data collection the participants completed the dynamic WU only followed (5-6 minutes) by the participants completing two trials of SLJs separated by 2-3 minutes. A paired t-test was used to compare the maximum SLJ between WU conditions and a Pearson correlation coefficient (r) was calculated to compare 1-RM DLs with SLJ scores. The SLJ was significantly greater (4.3±7.5 cm) following the 1-RM DL PAP warm-up (p

Lurbinectedin (PM01183) is a new synthetic tetrahydroisoquinoline alkaloid that binds to selected sequences in the minor groove of DNA, inducing PM01183-DNA adducts that stall replication, DNA repair and transcription and gives rise to double-strand breaks and finally, caspase-dependent apoptotic cell death. PM01183 has demonstrated clinical antitumor activity in platinum resistant/refractory ovarian cancer patients. A rapid and sensitive liquid chromatography/tandem mass spectrometry assay was developed and validated to quantify PM01183 in plasma from nonclinical species. The bioanalysis consisted of a supported liquid extraction, followed by a gradient phase chromatography and, detection by positive ion electrospray tandem mass spectrometry. The calibration range for PM01183 was established using PM01183 standards from 0.1 to 100 ng/mL in blank plasma. The multiple reaction monitoring, based on the transition m/z 767.3→273.0, was specific for PM01183, and that based on the transition m/z 771.4→277.0 was specific for the internal standard (deuterated PM01183). No endogenous material interfered with the analysis of PM01183 and the internal standard from blank plasma. The limit of detection (LOD) of the assay was calculated as 0.025 ng/mL. The correlation coefficients for the calibration curves ranged from 0.9937 to 0.9987. The mean inter-day accuracies for all calibration standards ranged from 92 to 108% (≤8% bias), and the mean inter-day precision for calibration standards was always less than 12%. The mean intra and inter-day assay accuracy for all quality control replicates remained between 91 and 109%. The mean intra and inter-day assay precision was less than 10% for all QC levels. The method was validated to demonstrate the specificity, recovery, limit of quantification, accuracy and precision of measurements. The assay has been used to support preclinical pharmacokinetic and toxicokinetic studies of PM01183 in nonclinical species. The main PK parameters in dogs (3 male and 3 female, respectively) were calculated as follows: maximum concentration (Cmax, 12.9±0.6 and 10.2±3.0 ng/mL) and the area under the plasma concentration-time curve (AUC, 24.9±0.7 and 22.6±6.1 ng h/mL). The results showed that plasma samples could be monitored for PM01183 for long enough to accurately estimate pharmacokinetics information.

Crossfit participation has experienced exponential growth. Like other sports, it may be that successful participation in Crossfit would rely upon a construct known as grit. Grit is considered to be a combination of perseverance of effort (PE) and consistency of interest (CI) and has been assessed in other populations with the 12-point Grit Scale. The ability to reliably assess grit among Crossfit participants may allow participants and coaches to monitor the constructs of PE and CI in order to further develop Crossfit participation skills. Hence, the purpose of this study was to examine the reliability of the 12-point Grit Scale among adult Crossfit participants. The 12-point Grit Scale was electronically administered twice to 25 adult Crossfit participants (female:11, male:14) separated by at least two weeks. The results of the two administrations of the 12-point Grit Scale were then compared with a battery of statistical analyses in order to assess the reliability of the 12-point Grit Scale. The test-retest 12-point Grit Scale scores were: 49.8±5.3 and 50.2±5.4. The reliability statistics along with 90% confidence limits were as follows: interclass reliability coefficient was r=0.87 (UL:0.94, LL:0.73), intraclass reliability coefficient was ICC=0.91 (UL:0.96, LL:0.83), Standard Error of Measurement (SEm)=1.6 (UL:2.2, LL:1.3), ∆Means 12-point Grit Scores= -0.3±2.3 (UL:0.6, LL:-1.2), and typical error CV% =3.4 (UL:4.8, LL:2.7). The Bland-Altman plot suggested agreement between the two administrations of the 12-point Grit Scale with no evidence of heteroscedasticity. The results of the 12-point Grit Scale and subscales ranged from moderately-high to excellent reliability among adult Crossfit participants.

This presentation describes the mission of LANL, its projects, funding portfolio, and collaborations.

This study determined if an eccentrically loaded deadlift yields a higher 1 repetition maximum (1RM) and 3RM than a conventional deadlift and if the 1RM conventional and eccentrically loaded deadlift can be accurately estimated from the 3RM (3RM = 93% of 1RM). Division 1 football players (n = 15; 20.3 ± 1.9 years; 95.8 ± 18.2 kg; 184.4 ± 6.6 cm) participated. Deadlift 1RM and 3RM were measured in the conventional and eccentrically loaded deadlift. Dependent t-tests showed no significant difference between the 3RM and 1RM conventional deadlift and the 3RM and 1RM eccentrically loaded deadlift (p = 0.30 and p = 0.20, respectively). Pearson correlation between the 1RM conventional deadlift estimate and 1RM conventional deadlift actual was r = 0.91 (p ≤ 0.01); a dependent t-test indicated the 1RM conventional deadlift estimate was significantly less than the 1RM conventional deadlift actual (p = 0.007). Pearson correlation between the 1RM eccentrically loaded deadlift estimate and 1RM eccentrically loaded deadlift actual was r = 0.84 (p ≤ 0.01); a dependent t-test indicated the 1RM eccentrically loaded deadlift estimate was nearly significantly less than the 1RM eccentrically loaded deadlift actual (p = 0.061). Results suggest that conventional and eccentrically loaded deadlifts may be interchangeable within a training program; this may elicit the benefits of using a broader variety of ground-based multijoint compound movements in an athlete's strength and power training. Additionally, because of differences between predicted and actual 1RM scores in the deadlift, strength coaches should prioritize actual 1RM testing of their athletes to optimize deadlift training loads across the RM continuum.

Recent evidence demonstrates that peripheral immune cells contribute to the nociceptive hypersensitivity associated with neuropathic pain by infiltrating the central nervous system (CNS). We have recently developed a rat model of graded chronic constriction injury (CCI) by varying the exposure of the sciatic nerve and control non-nerve tissue to surgical placement of chromic gut. We demonstrate that splenocytes can contribute significantly to CCI-induced allodynia, as adoptive transfer of these cells from high pain donors to low pain recipients potentiates allodynia (P0.001). The phenomenon was replicated with peripheral blood mononuclear cells (P0.001). Adoptive transfer of allodynia was not achieved in sham recipients, indicating that peripheral immune cells are only capable of potentiating existing allodynia, rather than establishing allodynia. As adoptively transferred cells were found by flow cytometry to migrate to the spleen (P0.05) and potentiation of allodynia was prevented in splenectomised low pain recipients, adoptive transfer of high pain splenocytes may induce the migration of host-derived immune cells from the spleen to the CNS as observed by flow cytometry (P0.05). Importantly, intrathecal transfer of CD45(+) cells prepared from spinal cords of high pain donors into low pain recipients led to potentiated allodynia (P0.001), confirming that infiltrating immune cells are not passive bystanders, but actively contribute to nociceptive hypersensitivity in the lumbar spinal cord.

Nine observers reviewed a previously assembled library of 320 chest computed radiography (CR) images. Observers participated in four sessions, reading a different 1/4 of the sample on each of four liquid crystal displays: a 2-megapixel (MP) consumer color display, a 2-MP business color display, a 2-MP medical-grade gray display, and a 3-MP gray display. Each display was calibrated according to the DICOM Part 14 standard. The viewing application required observer login, then randomized the order of the subsample seen on the display, and timed the responses of the observer to render a 1–5 judgment on the absence or presence of ILD on chest CRs. Selections of 1–2 were considered negative, 3 was indeterminate, and 4–5 were positive. The order of viewing sessions was also randomized for each observer. The experiment was conducted under controlled lighting, temperature, and sound conditions to mimic conditions typically found in a patient examination room. Lighting was indirect, and illuminance at the display face was 195 ± 8% lux and was monitored over the course of the experiment. The average observer sensitivity for the 2 MP color consumer, 2 MP business color, 2 MP gray, and 3 MP gray displays were 83.7%, 84.1%, 85.5%, and 86.7%, respectively. The only pairwise significant difference was between the 2-MP consumer color and the 2-MP gray (P = 0.05). Effect of order within a session was not signitfficant (P = 0.21): period 1 (84.3%), period 2 (86.2%), period 3 (85.4%), period 4 (84.1%). Observer specificity for the various displays was not statistically significant (P = 0.21). Finally, a timing analysis showed no significant difference between the displays for the user group (P = 0.13), ranging from 5.3 s (2 MP color business) to 5.9 s (3 MP Gray). There was, however, a reduction in time over the study that was significant (P <<< 0.001) for all users; the group average decreased from 6.5 to 4.7 s per image. Physical measurements of the resolution, contrast, and noise properties of the displays were acquired. Most notably, the noise of the displays varied by 3.5× between the lowest and highest noise displays. Differences in display noise were indicative of observer performance. However, the large difference in the magnitude of the noise was not predictive of the small difference (3%) in the observer sensitivity for various displays. This is likely because detection of interstitial lung disease is limited by “““““anatomical noise””” rather than display or x-ray image noise.

Background: PM060184 is new marine derived tubulin-binding agent originally isolated from the sponge Lithoplocamia lithistoides. PM060184 has shown potent antitumor activity in vivo against a panel of different tumor xenografted models such as colon, gastric, NSCLC, prostate and renal. Also, PM060184 has demonstrated to have a potent in vitro and in vivo activity in P-gp overexpressing cells. PM060184 is currently under evaluation in Phase I clinical studies in patients with advanced cancer diseases. Material and Methods: Athymic female nu/nu mice were subcutaneously implanted with H460 (NSCLC). Tumor bearing animals were randomly allocated into experimental groups (efficacy or pharmacokinetics -PK-). The animals belonging to the efficacy study received three iv doses in a weekly (q7dx3) schedule of PM060184 at 16 mg/kg or placebo. The antitumor activity was followed by the change in tumor volume for treated and placebo groups. The PK group received a single dose of PM060184 at 16 mg/kg. Then, plasma, tissue (brain, spleen, lung, muscle and heart) and tumor samples (N=3-4/sampling time) were collected at different times and up to 96 h post-administration. Tissue and tumor samples were diluted and homogenized using Precellys®24 bead beating technology. Once homogenized the samples were processed as per plasma. PM060184 was detected in plasma, tissue and tumor extracts by electrospray ionization/tandem mass spectrometry after extraction by supported liquid extraction (SLE). Results: The mean maximum plasma concentration (Cmax) was 2,452.5 ng/mL. The area under curve (AUC) was 2,963 ng*hr/mL. The plasma clearance was 5,398.5 mL/hr/kg. The volume of distribution at steady state was 880.7 mL/kg. The terminal half-life was 4.7 hr. The AUC0-tlast values for brain, spleen, lung, muscle and heart were 216.2, 7,402.9, 3,857.7, 2,614.6 and 2,929.5 ng*hr/g, respectively; however the AUC value for H460 xenografted tumors was 51,321.4 ng*hr/g (tlast is 96 hours for tumor, 8 hours for brain and 24 hours for the other tissues). Conclusion: PM060184 showed similar plasma and tissue pharmacokinetics properties as well as preferential tumor distribution until 96 h after an iv administration in mice bearing H460 xenografted tumors. Citation Format: Tiziana Pernice, Alan Bishop, Oscar Cataluña, Mandy Palomares, Raquel Lopez, Práxedes Núñez, Carmen Cuevas, Maria José Guillén, Pablo M. Aviles. Plasma, tissue and tumor pharmacokinetics of PM060184 in NSCL xenograft mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4654. doi:10.1158/1538-7445.AM2014-4654

Background: PM01183 is a new alkaloid that binds to the minor groove of DNA and causes cell cycle perturbations, mainly consisting in a delayed progression of S phase and cycle arrest in G2/M. T Currently, PM01183 clinical development includes Phase II single agent trials (pancreas, breast and platinum-resistant/refractory ovarian) as well as Phase I trials in combination (with doxorubicin and gemcitabine) and in advanced acute leukemia. The antitumor in vivo activity, as well as plasma and tumor pharmacokinetics in breast and pancreatic tumor xenografted models are presented here. Material and Methods: Athymic female nu/nu mice were subcutaneously implanted with SW1990 (pancreas) or MDA-MB-231 (breast) cells. When tumors reached ca. 300 mm3, tumor bearing animals were randomly allocated into experimental groups (efficacy, placebo and pharmacokinetics -PK-). The animals belonging to the efficacy study received three doses in a weekly (q7dx3) schedule of PM01183 at 0.18 mg/kg or placebo. The antitumor activity was followed by the change in tumor volume for treated and placebo groups. The PK group received a single dose of PM01183 at 0.18 mg/kg. Then, plasma and tumor samples (N=3-4/sampling time) were collected at different times and up to 24 h post-administration. Tumor samples were diluted 1:4 w/v with water and homogenized using Precellys®24 bead beating technology. Once homogenized the samples were processed as per plasma. PM01183 was detected in plasma and tumor extracts by electrospray ionization/tandem mass spectrometry after extraction by supported liquid extraction (SLE). The lower limit of quantitation (LLOQ) for plasma samples was 0.1 ng/mL. The LLOQ for breast and pancreas tumors were 0.5 and 1 ng/g tumor, respectively. Results: PM01183 induced statistically significant antitumor activity in both SW 1990 (P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1779. doi:1538-7445.AM2012-1779

The primary recurrent theme in ‘soliton physics’ as it is now evolving [1] in statistical physics, critical phenomena and condensed-matter physics generally (as well as quantum-field theory and gravity, etc.), is the simple recognition that linearization schemes are frequently misleading and (as witnessed by the contents of this Symposium) sometimes unnecessary. It is increasingly appreciated that we need to go beyond (linear) normal modes and finite-order perturbation theories in a spectrum of intrinsically nonlinear problems for which distinctive nonlinear, e.g., soliton, sectors of solution space are possible. Since the physical signatures of nonlinear modes, particularly spatially-limited ones, are often so crucial, it is essential that they are fully represented. In this situation, there is a growing tendency to develop theories which ab initio include all fundamental modes (including nonlinear ones) even if this is only possible semi-quantitatively. Such an approach has well-established precedents, e.g., phonon-roton gas models in liquid-helium-4 or vortices in superconductors.