Modelling the nucleon wave function from soft and hard processes

Current light-cone wave functions for the nucleon are unsatisfactory since they are in conflict with the data of the nucleon's Dirac form factor at large momentum transfer. Therefore, we attempt a determination of a new wave function respecting theoretical ideas on its parameterization and satisfying the following constraints: It should provide a soft Feynman contribution to the proton's form factor in agreement with data; it should be consistent with current parameterizations of the valence quark distribution functions and lastly it should provide an acceptable value for the \jp \to N \bar N decay width. The latter process is calculated within the modified perturbative approach to hard exclusive reactions. A simultaneous fit to the three sets of data leads to a wave function whose $x$-dependent part, the distribution amplitude, shows the same type of asymmetry as those distribution amplitudes constrained by QCD sum rules. The asymmetry is however much more moderate as in those amplitudes. Our distribution amplitude resembles the asymptotic one in shape but the position of the maximum is somewhat shifted.Comment: 32 pages RevTex + PS-file with 5 figures in uu-encoded, compressed fil

Pharmacological Targeting of Native CatSper Channels Reveals a Required Role in Maintenance of Sperm Hyperactivation

The four sperm-specific CatSper ion channel proteins are required for hyperactivated motility and male fertility, and for Ca2+ entry evoked by alkaline depolarization. In the absence of external Ca2+, Na+ carries current through CatSper channels in voltage-clamped sperm. Here we show that CatSper channel activity can be monitored optically with the [Na+]i-reporting probe SBFI in populations of intact sperm. Removal of external Ca2+ increases SBFI signals in wild-type but not CatSper2-null sperm. The rate of the indicated rise of [Na+]i is greater for sperm alkalinized with NH4Cl than for sperm acidified with propionic acid, reflecting the alkaline-promoted signature property of CatSper currents. In contrast, the [Na+]i rise is slowed by candidate CatSper blocker HC-056456 (IC50 ∼3 µM). HC-056456 similarly slows the rise of [Ca2+]i that is evoked by alkaline depolarization and reported by fura-2. HC-056456 also selectively and reversibly decreased CatSper currents recorded from patch-clamped sperm. HC-056456 does not prevent activation of motility by HCO3− but does prevent the development of hyperactivated motility by capacitating incubations, thus producing a phenocopy of the CatSper-null sperm. When applied to hyperactivated sperm, HC-056456 causes a rapid, reversible loss of flagellar waveform asymmetry, similar to the loss that occurs when Ca2+ entry through the CatSper channel is terminated by removal of external Ca2+. Thus, open CatSper channels and entry of external Ca2+ through them sustains hyperactivated motility. These results indicate that pharmacological targeting of the CatSper channel may impose a selective late-stage block to fertility, and that high-throughput screening with an optical reporter of CatSper channel activity may identify additional selective blockers with potential for male-directed contraception

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Endovascular Stent Treatment for Symptomatic Benign Iliofemoral Venous Occlusive Disease: Long-Term Results 1987–2009

Venous stenting has been shown to effectively treat iliofemoral venous obstruction with good short- and mid-term results. The aim of this study was to investigate long-term clinical outcome and stent patency. Twenty patients were treated with venous stenting for benign disease at our institution between 1987 and 2005. Fifteen of 20 patients (15 female, mean age at time of stent implantation 38 years [range 18–66]) returned for a clinical visit, a plain X-ray of the stent, and a Duplex ultrasound. Four patients were lost to follow-up, and one patient died 277 months after stent placement although a good clinical result was documented 267 months after stent placement. Mean follow-up after stent placement was 167.8 months (13.9 years) (range 71 (6 years) to 267 months [22 years]). No patient needed an additional venous intervention after stent implantation. No significant difference between the circumference of the thigh on the stented side (mean 55.1 cm [range 47.0–70.0]) compared with the contralateral thigh (mean 54.9 cm [range 47.0–70.0]) (p = 0.684) was seen. There was a nonsignificant trend toward higher flow velocities within the stent (mean 30.8 cm/s [range 10.0–48.0]) and the corresponding vein segment on the contralateral side (mean 25.2 cm/s [range 12.0–47.0]) (p = 0.065). Stent integrity was confirmed in 14 of 15 cases. Only one stent showed a fracture, as documented on x-ray, without any impairment of flow. Venous stenting using Wallstents showed excellent long-term clinical outcome and primary patency rate

Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

BACKGROUND: Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. METHODS: Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. RESULTS: This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. CONCLUSION: This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion

Comparison of 1- and 2-year screening intervals for women undergoing screening mammography

We compared the long-term impact of 1- and 2-year screening mammography intervals using prognostic, screening, and outcome information for women aged 50–74 years obtained from the Screening Mammography Program of British Columbia in two time periods, prior to 1997 (policy of annual mammography) and after 1997 (biennial mammography). Survival was estimated for both periods using a prognostic model and the expected rate of interval and screen-detected cancers. The likelihood of a screen-detected cancer with annual screening was 2.32 per thousand screens and with biennial screening was 3.32 per thousand screens. The prognostic profile of screen-detected cancers was better than that of interval cancers. Among both screen-detected and interval cancers, the prognostic profiles with annual and biennial screening were similar. The estimated breast cancer-specific survival rates for women undergoing annual and biennial screening mammography were 95.2 and 94.6% at 5 years, and 90.4 and 89.2% at 10 years, respectively. Annual compared to biennial mammography was associated with a 1.2% increase in the estimated 10-year breast cancer-specific survival for women aged 50–74 years, diagnosed with invasive breast cancer after screening programme attendance

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage

Genomic resolution of linkages in carbon, nitrogen, and sulfur cycling among widespread estuary sediment bacteria

Abstract Background Estuaries are among the most productive habitats on the planet. Bacteria in estuary sediments control the turnover of organic carbon and the cycling of nitrogen and sulfur. These communities are complex and primarily made up of uncultured lineages, thus little is known about how ecological and metabolic processes are partitioned in sediments. Results De novo assembly and binning resulted in the reconstruction of 82 bacterial genomes from different redox regimes of estuary sediments. These genomes belong to 23 bacterial groups, including uncultured candidate phyla (for example, KSB1, TA06, and KD3-62) and three newly described phyla (White Oak River (WOR)-1, WOR-2, and WOR-3). The uncultured phyla are generally most abundant in the sulfate-methane transition (SMTZ) and methane-rich zones, and genomic data predict that they mediate essential biogeochemical processes of the estuarine environment, including organic carbon degradation and fermentation. Among the most abundant organisms in the sulfate-rich layer are novel Gammaproteobacteria that have genes for the oxidation of sulfur and the reduction of nitrate and nitrite. Interestingly, the terminal steps of denitrification (NO3 to N2O and then N2O to N2) are present in distinct bacterial populations. Conclusions This dataset extends our knowledge of the metabolic potential of several uncultured phyla. Within the sediments, there is redundancy in the genomic potential in different lineages, often distinct phyla, for essential biogeochemical processes. We were able to chart the flow of carbon and nutrients through the multiple geochemical layers of bacterial processing and reveal potential ecological interactions within the communities.http://deepblue.lib.umich.edu/bitstream/2027.42/111044/1/40168_2015_Article_77.pd

A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation

BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology