Photoassociation and coherent transient dynamics in the interaction of ultracold rubidium atoms with shaped femtosecond pulses - I. Experiment

We experimentally investigate various processes present in the photoassociative interaction of an ultracold atomic sample with shaped femtosecond laser pulses. We demonstrate the photoassociation of pairs of rubidium atoms into electronically excited, bound molecular states using spectrally cut femtosecond laser pulses tuned below the rubidium D1 or D2 asymptote. Time-resolved pump-probe spectra reveal coherent oscillations of the molecular formation rate, which are due to coherent transient dynamics in the electronic excitation. The oscillation frequency corresponds to the detun-ing of the spectral cut position to the asymptotic transition frequency of the rubidium D1 or D2 lines, respectively. Measurements of the molecular photoassociation signal as a function of the pulse energy reveal a non-linear dependence and indicate a non-perturbative excitation process. Chirping the association laser pulse allowed us to change the phase of the coherent transients. Furthermore, a signature for molecules in the electronic ground state is found, which is attributed to molecule formation by femtosecond photoassociation followed by spontaneous decay. In a subsequent article [A. Merli et al., submitted] quantum mechanical calculations are presented, which compare well with the experimental data and reveal further details about the observed coherent transient dynamics

Microbiome sharing between children, livestock and household surfaces in western Kenya

The gut microbiome community structure and development are associated with several health outcomes in young children. To determine the household influences of gut microbiome structure, we assessed microbial sharing within households in western Kenya by sequencing 16S rRNA libraries of fecal samples from children and cattle, cloacal swabs from chickens, and swabs of household surfaces. Among the 156 households studied, children within the same household significantly shared their gut microbiome with each other, although we did not find significant sharing of gut microbiome across host species or household surfaces. Higher gut microbiome diversity among children was associated with lower wealth status and involvement in livestock feeding chores. Although more research is necessary to identify further drivers of microbiota development, these results suggest that the household should be considered as a unit. Livestock activities, health and microbiome perturbations among an individual child may have implications for other children in the household

Age-based disparities in end-of-life decisions in Belgium: a population-based death certificate survey

<p>Abstract</p> <p>Background</p> <p>A growing body of scientific research is suggesting that end-of-life care and decision making may differ between age groups and that elderly patients may be the most vulnerable to exclusion of due care at the end of life. This study investigates age-related disparities in the rate of end-of-life decisions with a possible or certain life shortening effect (ELDs) and in the preceding decision making process in Flanders, Belgium in 2007, where euthanasia was legalised in 2002. Comparing with data from an identical survey in 1998 we also study the plausibility of the ‘slippery slope’ hypothesis which predicts a rise in the rate of administration of life ending drugs without patient request, especially among elderly patients, in countries where euthanasia is legal.</p> <p>Method</p> <p>We performed a post-mortem survey among physicians certifying a large representative sample (n = 6927) of death certificates in 2007, identical to a 1998 survey. Response rate was 58.4%.</p> <p>Results</p> <p>While the rates of non-treatment decisions (NTD) and administration of life ending drugs without explicit request (LAWER) did not differ between age groups, the use of intensified alleviation of pain and symptoms (APS) and euthanasia/assisted suicide (EAS), as well as the proportion of euthanasia requests granted, was bivariately and negatively associated with patient age. Multivariate analysis showed no significant effects of age on ELD rates. Older patients were less often included in decision making for APS and more often deemed lacking in capacity than were younger patients. Comparison with 1998 showed a decrease in the rate of LAWER in all age groups except in the 80+ age group where the rate was stagnant.</p> <p>Conclusion</p> <p>Age is not a determining factor in the rate of end-of-life decisions, but is in decision making as patient inclusion rates decrease with old age. Our results suggest there is a need to focus advance care planning initiatives on elderly patients. The slippery slope hypothesis cannot be confirmed either in general or among older people, as since the euthanasia law fewer LAWER cases were found.</p

Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers

<p>Abstract</p> <p>Background</p> <p>Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways.</p> <p>Methods</p> <p>We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts.</p> <p>Results</p> <p>Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer.</p> <p>Conclusion</p> <p>A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.</p

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component

Male breast cancer in BRCA1 and BRCA2 mutation carriers : pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.Peer reviewe