The Physical Demands of NCAA Division I Women\u27s College Soccer

Extensive research into women\u27s collegiate soccer is scarce, leaving gaps in the literature with little information available detailing the physical demands at different standards of play. Our purpose was to elucidate the physical demands of the Division I collegiate level and identify differences between playing positions. Twenty-three field players were observed during four competitive seasons using 10-Hz GPS units (Catapult Sports, Melbourne, Australia). Descriptive statistics and 95% confidence intervals were used to determine group and position-specific physical demands. Linear mixed modelling (LMM) was used to compare attacker, midfielder, and defender position groups. Total distance, high-speed distance, and sprint distance were 9486 ± 300 m, 1014 ± 118 m, and 428 ± 70 m, respectively. Furthermore, attackers were observed to cover the greatest distance at all speeds compared to midfielders and defenders. Our findings suggest that the physical demands of Division I women\u27s soccer differ by position and appear lower compared to higher standards of play. Therefore, coaches and sports scientists responsible for the physical training of Division I collegiate players should consider the specific physical demands of the collegiate level and playing position when prescribing training, as well as in the development of their annual training programs

Fluorescent analogues of Human α-Calcitonin Gene-Related Peptide with vasodilator potency

Human α-calcitonin gene-related peptide (h-α-CGRP) is a highly potent vasodilator peptide that belongs to the family of calcitonin peptides. There are two forms of CGRP receptors in humans and rodents: α-CGRP receptor predominately found in the cardiovascular system and β-CGRP receptor predominating in the gastrointestinal tract. The CGRP receptors are primarily localized to C and Aδ sensory fibers, where they are involved in nociceptive transmission and migraine pathophysiology. These fibers are found both peripherally and centrally, with extensive perivascular location. The CGRP receptors belong to the class B G-protein-coupled receptors, and they are primarily associated to signaling via Gα proteins. The objectives of the present work were: (i) synthesis of three single-labelled fluorescent analogues of h-α-CGRP by 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis, and (ii) testing of their biological activity in isolated human, mouse, and rat arteries by using a small-vessel myograph setup. The three analogues were labelled with 5(6)-carboxyfluorescein via the spacer 6-aminohexanoic acid at the chain of Lys24 or Lys35. Circular dichroism (CD) experiments were performed to obtain information on the secondary structure of these fluorescently labelled peptides. The CD spectra indicated that the folding of all three analogues was similar to that of native α-CGRP. The three fluorescent analogues of α-CGRP were successfully prepared with a purity of >95%. In comparison to α-CGRP, the three analogues exhibited similar efficacy, but different potency in producing a vasodilator effect. The analogue labelled at the N-terminus proved to be the most readily synthesized, but it was found to possess the lowest vasodilator potency. The analogues labelled at Lys35 or Lys24 exhibited an acceptable reduction in potency (i.e., 3–5 times and 5–10 times less potent, respectively), and thus they have potential for use in further investigations of receptor internalization and neuronal reuptake

Upper limits for undetected trace species in the stratosphere of Titan

In this paper we describe a first quantitative search for several molecules in Titan's stratosphere in Cassini CIRS infrared spectra. These are: ammonia (NH3), methanol (CH3OH), formaldehyde (H2CO), and acetonitrile (CH3CN), all of which are predicted by photochemical models but only the last of which observed, and not in the infrared. We find non-detections in all cases, but derive upper limits on the abundances from low-noise observations at 25{\deg}S and 75{\deg}N. Comparing these constraints to model predictions, we conclude that CIRS is highly unlikely to see NH3 or CH3OH emissions. However, CH3CN and H2CO are closer to CIRS detectability, and we suggest ways in which the sensitivity threshold may be lowered towards this goal.Comment: 11 pages plus 6 figure file

Plate-based diversity subset screening generation 2: An improved paradigm for high throughput screening of large compound files

High throughput screening (HTS) is an effective method for lead and probe discovery that is widely used in industry and academia to identify novel chemical matter and to initiate the drug discovery process. However, HTS can be time-consuming and costly and the use of subsets as an efficient alternative to screening these large collections has been investigated. Subsets may be selected on the basis of chemical diversity, molecular properties, biological activity diversity, or biological target focus. Previously we described a novel form of subset screening: plate-based diversity subset (PBDS) screening, in which the screening subset is constructed by plate selection (rather than individual compound cherry-picking), using algorithms that select for compound quality and chemical diversity on a plate basis. In this paper, we describe a second generation approach to the construction of an updated subset: PBDS2, using both plate and individual compound selection, that has an improved coverage of the chemical space of the screening file, whilst only selecting the same number of plates for screening. We describe the validation of PBDS2 and its successful use in hit and lead discovery. PBDS2 screening became the default mode of singleton (one compound per well) HTS for lead discovery in Pfizer

Environmental risk factors for Toxoplasma gondii infections and the impact of latent infections on allostatic load in residents of Central North Carolina

Abstract Background Toxoplasma gondii infection can be acquired through ingestion of infectious tissue cysts in undercooked meat or environmental oocysts excreted by cats. This cross-sectional study assessed environmental risk factors for T. gondii infections and an association between latent infections and a measure of physiologic dysregulation known as allostatic load. Methods Serum samples from 206 adults in the Durham-Chapel Hill, North Carolina area were tested for immunoglobulin (IgG) responses to T. gondii using commercial ELISA kits. Allostatic load was estimated as a sum of 15 serum biomarkers of metabolic, neuroendocrine and immune functions dichotomized at distribution-based cutoffs. Vegetated land cover within 500 m of residences was estimated using 1 m resolution data from US EPA’s EnviroAtlas. Results Handling soil with bare hands at least weekly and currently owning a cat were associated with 5.3 (95% confidence limits 1.4; 20.7) and 10.0 (2.0; 50.6) adjusted odds ratios (aOR) of T. gondii seropositivity, respectively. There was also a significant positive interaction effect of handling soil and owning cats on seropositivity. An interquartile range increase in weighted mean vegetated land cover within 500 m of residence was associated with 3.7 (1.5; 9.1) aOR of T. gondii seropositivity. Greater age and consumption of undercooked pork were other significant predictors of seropositivity. In turn, T. gondii seropositivity was associated with 61% (13%; 130%) greater adjusted mean allostatic load compared to seronegative individuals. In contrast, greater vegetated land cover around residence was associated with significantly reduced allostatic load in both seronegative (p < 0.0001) and seropositive (p = 0.004) individuals. Conclusions Residents of greener areas may be at a higher risk of acquiring T. gondii infections through inadvertent ingestion of soil contaminated with cat feces. T. gondii infections may partially offset health benefits of exposure to the natural living environment

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

LINE STRENGTHS OF R-BRANCH TRANSITIONS IN THE ν6\nu_{6} BAND OF H2O2H_{2}O_{2}

Author Institution: National Institute of Standards and TechnologyLine Strengths of several rotational-vibrational transitions in the R-branch of the $\nu_{6}$ band of $H_{2}O_{2}$ have been measured with a tunable diode laser spectrometer system. The resulting band strength has been derived from these measurements and was found to be $350 \pm 9 cm^{-2} atm^{-1}$ at 294.2 K. The total band strength was then calculated by applying appropriate partition functions resulting in $464 \pm 12 cm^{-2} amagat^{-1}$. Several self-broadening measurements were also made with an average value of $0.42 cm^{-1} atm^{-1}$

STATE-SPECIFIC DOUBLETS IN THE FTIR SPECTRUM OF GASEOUS TROPOLONE

Author Institution: Department of Chemistry and Biochemistry, Texas Tech University; Environmental Molecular Sciences Laboratory, Pacific Northwest National LaboratoryThe FTIR absorption spectrum of tropolone vapor at $25 {^{\circ}}C$ and 32 m path length has been recorded from 960 to about $700 cm^{-1}$ at a resolution of $0.0025 cm^{-1}$. Twenty-nine cold band and hot band spectral tunneling doublets are assigned. They are marked by sharp type A or type C Q branch spikes. Twenty-six vibration-contortion state-specific tunneling splittings are estimated for tropolone vapor in the ground electronic state. About half of these states show quenching of tunneling due to increased effective barriers and/or path lengths. The COH torsion and contortion fundamentals show resolved Q subband structure indicating vibration-contortion-rotation state-specific behavior. The analysis is guided by predictions of the independent (tunneling skeleton) (tunneling H atom) tautomerization model previously applied to the vibrational spectrum and tautomerization mechanism of tropolone. Several parallels are seen between the vibrational interactions arising in our studies of the tautomerization of tropolone and those appearing in recent articles discussing possible behaviors in the active sites of enzymatic H transfer reactions