Physical and physiological attributes of soccer goalkeepers - Should we rely only on means and standard deviations?

The purpose of this study was twofold: (a) to profile physical characteristics and physiological attributes of soccer goalkeepers (GKs) who were divided into three age groups – under 16 years, 16-19, and over 19, and (b) to examine the intra-individual variability among the GKs in each age group on all physical and physiological measurements performed in the study. The GKs underwent a series of physical (e.g., height, body mass, and percentage of body fat) and physiological (e.g., anaerobic profile, power and strength, and flexibility) tests. The three main findings of the current study were: (a) differences in physical characteristics and physiological attributes existed between GKs in the three age groups, (b) intra-individual variability can be found in most physical characteristics and physiological attributes of the GKs, and (c) the intra-individual variability was observed in all three groups. These findings emphasize the need for coaches to examine the intra-individual variability in GKs on their teams. These findings can be used by coaches when planning specific training programs for GKs of different age and skill levels

Role of electrolytes and unmeasured anions in the metabolic acid-base abnormalities in dogs with parvoviral enteritis

Background: The strong ion model (SIM) is an alternative paradigm in the characterization of acid‐base disturbances particularly in complex disorders. Hypothesis/Objectives: To compare the acid‐base changes in dogs with parvoviral enteritis (PE) using the Henderson‐Hasselbalch (HH) approach, with 2 strong ion approaches. Animals: Forty‐four dogs with PE, and 16 age‐matched control dogs. Methods: Prospective controlled observational study. Acid‐base status was evaluated using the HH model, Fencl‐Stewart (FS) approach and a validated strong ion model (VDM). The acid‐base changes according to each model were classified and compared. Statistical correlations between pH, CO2, and various SIM variables were performed, as well as between the sum of effects (SOE) of the SIM and the individual variables comprising the SOE. Results: The HH model identified acid‐base disorders in 31/44 cases of which 16/31 were mixed with metabolic acidosis and concurrent respiratory alkalosis the most common (10/31). Using the FS approach, metabolic changes were present 36/42 cases, with changes in free water (FW), chloride, and unmeasured anions (UA) being the most prevalent. Both FW and UA correlated well with pH; however, UA were most consistently abnormal in severe acidemia. Similarly to the HH, the VDM detected acid‐base disturbances in 28/44 cases. Major contributors to the acid‐base changes were hyponatremia, hypochloremia, and Atot acidosis because of elevated globulins and increased UA. Conclusions and Clinical Importance: Acid‐base changes are common and complex in dogs with PE, and were easier to understand using a SIM paradigm. Increases in UA have not been documented in PE in dogs

IOPs with Inverse Polynomial Soundness Error

We show that every language in NP has an Interactive Oracle Proof (IOP) with inverse polynomial soundness error and small query complexity. This achieves parameters that surpass all previously known PCPs and IOPs. Specifically, we construct an IOP with perfect completeness, soundness error $1/n$, round complexity $O(\log \log n)$, proof length $poly(n)$ over an alphabet of size $O(n)$, and query complexity $O(\log \log n)$. This is a step forward in the quest to establish the sliding-scale conjecture for IOPs (which would additionally require query complexity $O(1)$). Our main technical contribution is a high-soundness small-query proximity test for the Reed-Solomon code. We construct an IOP of proximity for Reed-Solomon codes, over a field $\mathbb{F}$ with evaluation domain $L$ and degree $d$, with perfect completeness, soundness error (roughly) $\max\{1-\delta , O(\rho^{1/4})\}$ for $\delta$-far functions, round complexity $O(\log \log d)$, proof length $O(|L|/\rho)$ over $\mathbb{F}$, and query complexity $O(\log \log d)$; here $\rho = (d+1)/|L|$ is the code rate. En route, we obtain a new high-soundness proximity test for bivariate Reed-Muller codes. The IOP for NP is then obtained via a high-soundness reduction from NP to Reed-Solomon proximity testing with rate $\rho = 1/poly(n)$ and distance $\delta = 1-1/poly(n)$ (and applying our proximity test). Our constructions are direct and efficient, and hold the potential for practical realizations that would improve the state-of-the-art in real-world applications of IOPs

A Toolbox for Barriers on Interactive Oracle Proofs

Interactive oracle proofs (IOPs) are a proof system model that combines features of interactive proofs (IPs) and probabilistically checkable proofs (PCPs). IOPs have prominent applications in complexity theory and cryptography, most notably to constructing succinct arguments. In this work, we study the limitations of IOPs, as well as their relation to those of PCPs. We present a versatile toolbox of IOP-to-IOP transformations containing tools for: (i) length and round reduction; (ii) improving completeness; and (iii) derandomization. We use this toolbox to establish several barriers for IOPs: -- Low-error IOPs can be transformed into low-error PCPs. In other words, interaction can be used to construct low-error PCPs; alternatively, low-error IOPs are as hard to construct as low-error PCPs. This relates IOPs to PCPs in the regime of the sliding scale conjecture for inverse-polynomial soundness error. -- Limitations of quasilinear-size IOPs for 3SAT with small soundness error. -- Limitations of IOPs where query complexity is much smaller than round complexity. -- Limitations of binary-alphabet constant-query IOPs. We believe that our toolbox will prove useful to establish additional barriers beyond our work

Harnessing Soluble NK Cell Killer Receptors for the Generation of Novel Cancer Immune Therapy

The natural cytotoxic receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The NCRs, which include three members; NKp46, NKp44 and NKp30, are critically involved in NK cytotoxicity against different targets, including a wide range of tumor cells derived from various origins. Even though the tumor ligands of the NCRs have not been identified yet, the selective manner by which these receptors target tumor cells may provide an excellent basis for the development of novel anti-tumor therapies. To test the potential use of the NCRs as anti-tumor agents, we generated soluble NCR-Ig fusion proteins in which the constant region of human IgG1 was fused to the extracellular portion of the receptor. We demonstrate, using two different human prostate cancer cell lines, that treatment with NKp30-Ig, dramatically inhibits tumor growth in vivo. Activated macrophages were shown to mediate an ADCC response against the NKp30-Ig coated prostate cell lines. Finally, the Ig fusion proteins were also demonstrated to discriminate between benign prostate hyperplasia and prostate cancer. This may provide a novel diagnostic modality in the difficult task of differentiating between these highly common pathological conditions

Granulosa Cell Endothelin-2 Expression is Fundamental for Ovulatory Follicle Rupture

Ovulation is dependent upon numerous factors mediating follicular growth, vascularization, and ultimately oocyte release via follicle rupture. Endothelin-2 (EDN2) is a potent vasoconstrictor that is transiently produced prior to follicle rupture by granulosa cells of periovulatory follicles and induces ovarian contraction. To determine the role of Edn2 expression, surgical transplant and novel conditional knockout mice were super-ovulated and analyzed. Conditional knockout mice utilized a new iCre driven by the Esr2 promoter to selectively remove Edn2. Follicle rupture and fertility were significantly impaired in the absence of ovarian Edn2 expression. When ovaries of Edn2KO mice were transplanted in wild type recipients, significantly more corpora lutea containing un-ovulated oocytes were present after hormonal stimulation (1.0 vs. 5.4, p = 0.010). Following selective ablation of Edn2 in granulosa cells, Esr2-Edn2KO dams had reduced oocytes ovulated (3.8 vs. 16.4 oocytes/ovary) and smaller litters (4.29 ± l.02 vs. 8.50 pups/dam). However, the number of pregnancies per pairing was not different and the reproductive axis remained intact. Esr2-Edn2KO ovaries had a higher percentage of antral follicles and fewer corpora lutea; follicles progressed to the antral stage but many were unable to rupture. Conditional loss of endothelin receptor A in granulosa cells also decreased ovulation but did not affect fecundity. These data demonstrate that EDN2-induced intraovarian contraction is a critical trigger of normal ovulation and subsequent fecundity

Fruit load governs transpiration of olive trees

We tested the hypothesis that whole-tree water consumption of olives (Olea europaea L.) is fruit load-dependent and investigated the driving physiological mechanisms. Fruit load was manipulated in mature olives grown in weighing-drainage lysimeters. Fruit was thinned or entirely removed from trees at three separate stages of growth: early, mid and late in the season. Tree-scale transpiration, calculated from lysimeter water balance, was found to be a function of fruit load, canopy size and weather conditions. Fruit removal caused an immediate decline in water consumption, measured as whole-plant transpiration normalized to tree size, which persisted until the end of the season. The later the execution of fruit removal, the greater was the response. The amount of water transpired by a fruit-loaded tree was found to be roughly 30% greater than that of an equivalent low- or nonyielding tree. The tree-scale response to fruit was reflected in stem water potential but was not mirrored in leaf-scale physiological measurements of stomatal conductance or photosynthesis. Trees with low or no fruit load had higher vegetative growth rates. However, no significant difference was observed in the overall aboveground dry biomass among groups, when fruit was included. This case, where carbon sources and sinks were both not limiting, suggests that the role of fruit on water consumption involves signaling and alterations in hydraulic properties of vascular tissues and tree organs.</p

Natural Killer Lysis Receptor (NKLR)/NKLR-Ligand Matching as a Novel Approach for Enhancing Anti-Tumor Activity of Allogeneic NK Cells

NK cells are key players in anti tumor immune response, which can be employed in cell-based therapeutic modalities. One of the suggested ways to amplify their anti tumor effect, especially in the field of stem cell transplantation, is by selecting donor/recipient mismatches in specific HLA, to reduce the inhibitory effect of killer Ig-like receptors (KIRs). Here we suggest an alternative approach for augmentation of anti tumor effect of allogeneic NK cells, which is founded on profile matching of donor NK lysis receptors (NKLR) phenotype with tumor lysis-ligands.We show that an NKLR-mediated killing directly correlates with the NKLR expression intensity on NK cells. Considerable donor variability in the expression of CD16, NKp46, NKG2D and NKp30 on circulating NK cells, combined with the stability of phenotype in several independently performed tests over two months, indicates that NKLR-guided selection of donors is feasible. As a proof of concept, we show that melanoma cells are dominantly recognized by three NKLRs: NKG2D, NKp30 and NKp44. Notably, the expression of NKp30 on circulating NK cells among metastatic melanoma patients was significantly decreased, which diminishes their ability to kill melanoma cells. Ex vivo expansion of NK cells results not only in increased amount of cells but also in a consistently superior and predictable expression of NKG2D, NKp30 and NKp44. Moreover, expanded NK cultures with high expression of NKG2D or NKp30 were mostly derived from the corresponding NKG2D(high) or NK30(high) donors. These NK cultures subsequently displayed an improved cytotoxic activity against melanoma in a HLA/KIR-ligand mismatched setup, which was NKLR-dependent, as demonstrated with blocking anti-NKG2D antibodies.NKLR/NKLR-ligand matching reproducibly elicits enhanced NK anti-tumor response. Common NKLR recognition patterns of tumors, as demonstrated here in melanoma, would allow implementation of this approach in solid malignancies and potentially in hematological malignancies, either independently or in adjunction to other modalities

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer

Background In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. Results Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. Conclusion Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC