Limitations and improvements upon the two-level approximation for molecular nonlinear optics

When parametric nonlinear processes are employed in the cause of efficient optical frequency conversion, the media involved are generally subjected to substantially off-resonant input radiation. As such, it is usually only electronic ground states of the conversion material that are significantly populated; higher levels are engaged only in the capacity of virtual states, and it is frequently assumed that just one such state dominates in determining the response. Calculating the nonlinear optical susceptibilities of molecules on this basis, excluding all but the ground and one excited state in a sum-over-states formulation, signifies the adoption of a two-level model, a technique that is widely deployed in the calculation and analysis of nonlinear optical properties. The two-level model offers tractable and physically simple representations of molecular response, including wavelength dependence; it is also the origin of the widely applied 'push-pull' approach to designing optically nonlinear chromophores. By contrast, direct ab initio calculations of optical susceptibility are commonly frustrated by a complete failure to determine such dispersion features. However, caution is required; the two-level model can deliver potentially misleading results if it is applied without regard to the criteria for its validity, especially when molecular excited states are significantly populated. On the basis of a precise, quantum electrodynamical basis for the theory, we explore in detail why there are grounds for questioning the general validity of two-level calculations in nonlinear optics; we assess the criteria for high frequency conversion efficiency and provide a new graphical method to assist in determining the applicability of a two-level model for hyperpolarizability calculations. Lastly, this paper also explores the applicability and detailed conditions for the two-level model for electronically excited molecules, identifying problematic results and providing tractable methods for improving the accuracy of calculations on real molecule-photon interactions

Impact of CTLA-4 checkpoint antibodies on ligand binding and Transendocytosis

Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically. Both have high affinity binding to CTLA-4 and occupy the ligand binding site, however recently it has been suggested that in some settings such antibodies may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities of these antibodies in a variety of settings using both soluble and cell bound target proteins. We found that when ligands (CD80 or CD86) were expressed on cells, soluble CTLA-4-Ig bound in line with affinity expectations and that this interaction was effectively disrupted by both ipilimumab and tremelimumab antibodies. Similarly, cellular CTLA-4 binding to soluble ligands was comparably prevented. We further tested the ability of these antibodies to block transendocytosis, whereby CTLA-4 captures ligands from target cells during a cognate cell-cell interaction. Once again ipilimumab and tremelimumab were similar in preventing removal of ligand by transendocytosis. Furthermore, even once transendocytosis was ongoing and cell contact was fully established, the addition of these antibodies could prevent further ligand transfer. Together these data indicate that the above checkpoint inhibitors performed in-line with predictions based on affinity and binding site data and are capable of blocking CTLA-4-ligand interactions in a wide range of settings tested

UJI KONSISTENSI PENENTUAN NILAI SAHAM-SAHAM INDUSTRI PROPERTI DAN REALESTATE YANG TERDAFTAR DI BURSA EFEK JAKARTA

The purpose of this research is to know whether profit growth, dividend payout ratio and deviation standard are determining the fair of stock price among period The population of the research is go public companies and samples taken are property and realestate industries already listed before January 1995 and the companies still listed on the Jakarta Stock Exchange still December 31th, 1999. The Data used in this research is secondary data i.e. Earning Per Share (EPS), Price Earning Ratio (PER) and standard deviation of each company from 1995 until 1997 as independent variables.The result of this research shows that: (1) profit growth, dividend payout ratio and deviation standard are together have real impact on price earning ratio, (2) among variables believed to price earning ratio predictors, profit growth, dividend payout ratio and deviation standard i.e 15.3%, 17.2% and 15.4% and (3) this research shows that the dominant impact of variables are different among period. The differences were in the significance level and the weight of influence of independent variable to the corresponding dependent variable. On the 1995, the influence variable is standard deviation but on the 1996 and 1997 the influence variable is profit growth

UJI KONSISTENSI PENENTUAN NILAI SAHAM-SAHAM INDUSTRI PROPERTI DAN REALESTATE YANG TERDAFTAR DI BURSA EFEK JAKARTA

The purpose of this research is to know whether profit growth, dividend payout ratio and deviation standard are determining the fair of stock price among period The population of the research is go public companies and samples taken are property and realestate industries already listed before January 1995 and the companies still listed on the Jakarta Stock Exchange still December 31th, 1999. The Data used in this research is secondary data i.e. Earning Per Share (EPS), Price Earning Ratio (PER) and standard deviation of each company from 1995 until 1997 as independent variables.The result of this research shows that: (1) profit growth, dividend payout ratio and deviation standard are together have real impact on price earning ratio, (2) among variables believed to price earning ratio predictors, profit growth, dividend payout ratio and deviation standard i.e 15.3%, 17.2% and 15.4% and (3) this research shows that the dominant impact of variables are different among period. The differences were in the significance level and the weight of influence of independent variable to the corresponding dependent variable. On the 1995, the influence variable is standard deviation but on the 1996 and 1997 the influence variable is profit growth

Evidence-based decision support for pediatric rheumatology reduces diagnostic errors.

BACKGROUND: The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagnostic accuracy of non-specialists. METHODS: Using vignettes of actual clinical cases, clinician testers generated a differential diagnosis before and after using diagnostic decision support software. The evaluation used the SimulConsult® DDSS tool, based on Bayesian pattern matching with temporal onset of each finding in each disease. The tool covered 5405 diseases (averaging 22 findings per disease). Rheumatology content in the database was developed using both primary references and textbooks. The frequency, timing, age of onset and age of disappearance of findings, as well as their incidence, treatability, and heritability were taken into account in order to guide diagnostic decision making. These capabilities allowed key information such as pertinent negatives and evolution over time to be used in the computations. Efficacy was measured by comparing whether the correct condition was included in the differential diagnosis generated by clinicians before using the software ( unaided ), versus after use of the DDSS ( aided ). RESULTS: The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p \u3c 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an open book approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software. CONCLUSIONS: These findings suggest that decision support can reduce diagnostic errors and improve use of relevant information by generalists. Such assistance could potentially help relieve the shortage of experts in pediatric rheumatology and similarly underserved specialties by improving generalists\u27 ability to evaluate and diagnose patients presenting with musculoskeletal complaints. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02205086

Approximation algorithms for hard variants of the stable marriage and hospitals/residents problems

When ties and incomplete preference lists are permitted in the Stable Marriage and Hospitals/Residents problems, stable matchings can have different sizes. The problem of finding a maximum cardinality stable matching in this context is known to be NP-hard, even under very severe restrictions on the number, size and position of ties. In this paper, we describe polynomial-time 5/3-approximation algorithms for variants of these problems in which ties are on one side only and at the end of the preference lists. The particular variant is motivated by important applications in large scale centralised matching schemes

Challenge for planning by using cluster methodology: the case study of the Algarve Region

This study analyses the most appropriate methodology to make similarity classifications among the cities of the Algarve (Portugal) according to 105 sustainability indicators monitored with the Observatory of Sustainability of the Algarve Region for Tourism (OBSERVE). The methodology used to establish the similarities was the cluster analysis with 4 different approaches which reduced the dimensions of the data set: total approach, pillar approach, subject area approach, and indicator approach. By combining the approaches, a total of 620 different cluster analyses were performed. There sults reflected that the data analysis approaches with less dimensions were those that performed the best groups among cities. In this sense, the approaches with a high number of indicators (e.g., the totalor the pillar approach) were characterised by misclassifying cities in more than 30% of the indicators.Thus, the most acceptable cluster analysis approach was that with a low number of indicators.Through this approach, it was possible to make correct groups of the sustainability level of the cities of the Algarve. These results provided an appropriate methodology for the decision-making regarding the sustainability of a region and could be extrapolated to other regions to assess sustainability or environmental indicator

Deletion of the von Hippel-Lindau gene causes sympathoadrenal cell death and impairs chemoreceptor-mediated adaptation to hypoxia

Mutations of the von Hippel–Lindau (VHL) gene are associated with pheochromocytomas and paragangliomas, but the role of VHL in sympathoadrenal homeostasis is unknown. We generated mice lacking Vhl in catecholaminergic cells. They exhibited atrophy of the carotid body (CB), adrenal medulla, and sympathetic ganglia. Vhl‐null animals had an increased number of adult CB stem cells, although the survival of newly generated neuron‐like glomus cells was severely compromised. The effects of Vhl deficiency were neither prevented by pharmacological inhibition of prolyl hydroxylases or selective genetic down‐regulation of prolyl hydroxylase‐3, nor phenocopied by hypoxia inducible factor overexpression. Vhl‐deficient animals appeared normal in normoxia but survived for only a few days in hypoxia, presenting with pronounced erythrocytosis, pulmonary edema, and right cardiac hypertrophy. Therefore, in the normal sympathoadrenal setting, Vhl deletion does not give rise to tumors but impairs development and plasticity of the peripheral O2‐sensing system required for survival in hypoxic conditions