Critical Analysis of Theoretical Estimates for BB to Light Meson Form Factors and the B→ψK(K∗)B \to \psi K(K^{\ast}) Data

We point out that current estimates of form factors fail to explain the non-leptonic decays $B \to \psi K(K^{\ast})$ and that the combination of data on the semi-leptonic decays $D \to K(K^{\ast})\ell \nu$ and on the non-leptonic decays $B \to \psi K(K^{\ast})$ (in particular recent po\-la\-ri\-za\-tion data) severely constrain the form (normalization and $q^2$ dependence) of the heavy-to-light meson form factors, if we assume the factorization hypothesis for the latter. From a simultaneous fit to \bpsi and \dk data we find that strict heavy quark limit scaling laws do not hold when going from $D$ to $B$ and must have large corrections that make softer the dependence on the masses. We find that $A_1(q^2)$ should increase slower with \qq than $A_2, V, f_+$. We propose a simple parametrization of these corrections based on a quark model or on an extension of the \hhs laws to the \hl case, complemented with an approximately constant $A_1(q^2)$. We analyze in the light of these data and theoretical input various theoretical approaches (lattice calculations, QCD sum rules, quark models) and point out the origin of the difficulties encountered by most of these schemes. In particular we check the compatibility of several quark models with the heavy quark scaling relations.Comment: 48 pages, DAPNIA/SPP/94-24, LPTHE-Orsay 94/1

Analysis on the clinical features of 22 basaloid squamous cell carcinoma of the lung

<p>Abstract</p> <p>Background</p> <p>Basaloid squamous cell carcinoma of the lung is a rare and highly malignant tumor mostly observed in the proximal bronchi. Basaloid squamous cell carcinoma of the lung cases typically show rapid clinical progression, very poor prognosis and special pathological morphology. This project aimed to examine the clinical features of basaloid squamous cell carcinoma of the lung and the factors related to its prognosis; and to compare survival outcomes between basaloid squamous cell carcinoma and poorly differentiated squamous cell carcinomas (PDSC).</p> <p>Methods</p> <p>Between January 2004 and December 2008, pathological sections from basaloid squamous cell carcinoma and PDSC of the lung were collected and retrospectively analyzed at Tianjin Medical University Cancer Institute and Hospital. Data analysis was performed using Statistical Package for the Social Sciences (SPSS11.0). The Kaplan-Meier method was used to calculate the survival rate. Log-rank test was used to compare the differences in survival rate between the two groups. The factors influencing prognosis were analyzed using the Cox proportional hazard model.</p> <p>Results</p> <p>A total of 120 pathological sections were used in the analysis of this study-22 from basaloid squamous cell carcinoma cases and 98 from PDSC cases. Compared to the PDSC group, the basaloid squamous cell carcinoma group had a larger proportion of female patients (p = 0.001); however it had higher proportion of male smokers (p = 0.003). There were no statistically significant differences in survival rate between the two groups (χ²= 1.200, p = 0.273). Additionally, prognosis of basaloid squamous cell carcinoma is significantly influenced by treatment mode and clinical stages of the tumor. The post-operation mortality hazard of patients treated with a combination chemotherapy and radiotherapy was 1.296 times higher than other treatment modes (<it>p </it>= 0.025). Increases in post-operation mortality hazard ratio were also associated with more advanced clinical stage of tumors (χ²trend = 11.907, <it>p </it>= 0.000).</p> <p>Conclusions</p> <p>This study demonstrated that basaloid squamous cell carcinoma and PDSC have very similar clinical features, and there are no significant differences in survival rates between the two groups. Hence, we conclude that in the short term, the same clinical treatments and therapeutic modes can be administered to patients with basaloid squamous cell carcinoma and PDSC of the lung.</p

Covariant quark model of form factors in the heavy mass limit

We show that quark models of current matrix-elements based on the Bakamjian-Thomas construction of relativistic states with a fixed number of particles, plus the additivity assumption, are covariant in the heavy-quark limit and satisfy the full set of heavy-quark symmetry relations discovered by Isgur and Wise. We find the lower bound of $\rho^2$ in such models to be $3/4$ for ground state mesons, independently of any parameter. Another welcome property of these models is that in the infinite momentum limit the wave functions vanish outside the domain $0\le x \le 1$.Comment: 16 page

Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients.</p> <p>Methods</p> <p>We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma.</p> <p>Results</p> <p>From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001).</p> <p>Conclusions</p> <p>This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.</p

Exploring the Factors Controlling the Error Characteristics of the Surface Water and Ocean Topography Mission Discharge Estimates

The Surface Water and Ocean Topography (SWOT) satellite mission will measure river width, water surface elevation, and slope for rivers wider than 50–100 m. SWOT observations will enable estimation of river discharge by using simple flow laws such as the Manning-Strickler equation, complementing in situ streamgages. Several discharge inversion algorithms designed to compute unobserved flow law parameters (e.g., friction coefficient and bathymetry) have been proposed, but to date, a systematic assessment of factors controlling algorithm performance has not been conducted. Here, we assess the performance of the five algorithms that are expected to be used in the construction of the SWOT product. To perform this assessment, we used synthetic SWOT observations created with hydraulic model output corrupted with SWOT-like error. Prior information provided to the algorithms was purposefully limited to an estimate of mean annual flow (MAF), designed to produce a “worst case” benchmark. Prior MAF error was an important control on algorithm performance, but discharge estimates produced by the algorithms are less biased than the MAF; thus, the discharge algorithms improve on the prior. We show for the first time that accuracy and frequency of remote sensing observations are less important than prior bias, hydraulic variability among reaches, and flow law accuracy in governing discharge algorithm performance. The discharge errors and error sensitivities reported herein are a bounding benchmark, representing worst possible expected errors and error sensitivities. This study lays the groundwork to develop predictive power of algorithm performance, and thus map the global distribution of worst-case SWOT discharge accuracy

Three Repeat Isoforms of Tau Inhibit Assembly of Four Repeat Tau Filaments

Tauopathies are defined by assembly of the microtubule associated protein tau into filamentous tangles and classified by the predominant tau isoform within these aggregates. The major isoforms are determined by alternative mRNA splicing of exon 10 generating tau with three (3R) or four (4R) ∼32 amino acid imperfect repeats in the microtubule binding domain. In normal adult brains there is an approximately equimolar ratio of 3R and 4R tau which is altered by several disease-causing mutations in the tau gene. We hypothesized that when 4R and 3R tau isoforms are not at equimolar ratios aggregation is favored. Here we provide evidence for the first time that the combination of 3R and 4R tau isoforms results in less in vitro heparin induced polymerization than with 4R preparations alone. This effect was independent of reducing conditions and the presence of alternatively spliced exons 2 and 3 N-terminal inserts. The addition of even small amounts of 3R to 4R tau assembly reactions significantly decreased 4R assembly. Together these findings suggest that co-expression of 3R and 4R tau isoforms reduce tau filament assembly and that 3R tau isoforms inhibit 4R tau assembly. Expression of equimolar amounts of 3R and 4R tau in adult humans may be necessary to maintain proper neuronal microtubule dynamics and to prevent abnormal tau filament assembly. Importantly, these findings indicate that disruption of the normal equimolar 3R to 4R ratio may be sufficient to drive tau aggregation and that restoration of the tau isoform balance may have important therapeutic implications in tauopathies

Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose.-nitrosothiols

Synchronous bilateral epithelial–myoepithelial carcinoma of the parotid gland: case report and review of the literature

Synchronous bilateral malignancy in the parotid glands is extremely rare. The English literature reveals nine case reports. The most common synchronous bilateral malignancies are acinic cell carcinoma. Epithelial–myoepithelial carcinoma is an uncommon neoplasm comprising 1% of all salivary gland tumours. In this case report, we describe, to our best of knowledge, the first case of a patient with a synchronous bilateral epithelial–myoepithelial carcinoma of the parotid gland. The clinical histopathological and immunohistochemical peculiarities are elucidated. Imaging studies like ultrasonography are mandatory for both parotid glands and upper necks in the clinical presence of a unilateral parotid gland tumour

Maternal environment shapes the life history and susceptibility to malaria of Anopheles gambiae mosquitoes

BACKGROUND: It is becoming generally recognized that an individual's phenotype can be shaped not only by its own genotype and environmental experience, but also by its mother's environment and condition. Maternal environmental factors can influence mosquitoes' population dynamics and susceptibility to malaria, and therefore directly and indirectly the epidemiology of malaria. METHODS: In a full factorial experiment, the effects of two environmental stressors - food availability and infection with the microsporidian parasite Vavraia culicis - of female mosquitoes (Anopheles gambiae sensu stricto) on their offspring's development, survival and susceptibility to malaria were studied. RESULTS: The offspring of A. gambiae s.s. mothers infected with V. culicis developed into adults more slowly than those of uninfected mothers. This effect was exacerbated when mothers were reared on low food. Maternal food availability had no effect on the survival of their offspring up to emergence, and microsporidian infection decreased survival only slightly. Low food availability for mothers increased and V. culicis-infection of mothers decreased the likelihood that the offspring fed on malaria-infected blood harboured malaria parasites (but neither maternal treatment influenced their survival up to dissection). CONCLUSIONS: Resource availability and infection with V. culicis of A. gambiae s.s. mosquitoes not only acted as direct environmental stimuli for changes in the success of one generation, but could also lead to maternal effects. Maternal V. culicis infection could make offspring more resistant and less likely to transmit malaria, thus enhancing the efficacy of the microsporidian for the biological control of malaria

The Effect of a ΔK280 Mutation on the Unfolded State of a Microtubule-Binding Repeat in Tau

Tau is a natively unfolded protein that forms intracellular aggregates in the brains of patients with Alzheimer's disease. To decipher the mechanism underlying the formation of tau aggregates, we developed a novel approach for constructing models of natively unfolded proteins. The method, energy-minima mapping and weighting (EMW), samples local energy minima of subsequences within a natively unfolded protein and then constructs ensembles from these energetically favorable conformations that are consistent with a given set of experimental data. A unique feature of the method is that it does not strive to generate a single ensemble that represents the unfolded state. Instead we construct a number of candidate ensembles, each of which agrees with a given set of experimental constraints, and focus our analysis on local structural features that are present in all of the independently generated ensembles. Using EMW we generated ensembles that are consistent with chemical shift measurements obtained on tau constructs. Thirty models were constructed for the second microtubule binding repeat (MTBR2) in wild-type (WT) tau and a ΔK280 mutant, which is found in some forms of frontotemporal dementia. By focusing on structural features that are preserved across all ensembles, we find that the aggregation-initiating sequence, PHF6*, prefers an extended conformation in both the WT and ΔK280 sequences. In addition, we find that residue K280 can adopt a loop/turn conformation in WT MTBR2 and that deletion of this residue, which can adopt nonextended states, leads to an increase in locally extended conformations near the C-terminus of PHF6*. As an increased preference for extended states near the C-terminus of PHF6* may facilitate the propagation of β-structure downstream from PHF6*, these results explain how a deletion at position 280 can promote the formation of tau aggregates